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emedicine.medscape.com EMEDICINE SPECIALTIES > DERMATOLOGY > DISEASES OF THE ADNEXA ALOPECIA AREATA Chantal Bolduc, MD, FRCP(C), Assistant Professor, Department of Dermatology, University of Montreal Harvey Lui, MD, FRCPC, Professor and Head, Department of Dermatology and Skin Science, Vancouver General Hospital, University of British Columbia; Medical Director, The Skin Centre, Lions Laser Skin Centre and Psoriasis and Phototherapy Clinic, Vancouver General Hospital; Jerry Shapiro, MD, FRCP(C), Clinical Associate Professor, Department of Medicine, Division of Dermatology, University of British Columbia, Canada Updated: Sep 27, 2010 INTRODUCTION BACKGROUND Alopecia areata is a recurrent nonscarring type of hair loss that can affect any hair-bearing area. Clinically, alopecia areata can manifest many different patterns. Although medically benign, alopecia areata can cause tremendous emotional and psychosocial distress in affected patients and their families. PATHOPHYSIOLOGY The exact pathophysiology of alopecia areata remains unknown. The most widely accepted hypothesis is that alopecia areata is a T-cell–mediated autoimmune condition that is most likely to occur in genetically predisposed individuals.[1 ] Autoimmunity 1 Falling Hair Problems & Probable cure… 6 January 2011 Much evidence supports the hypothesis that alopecia areata is an autoimmune condition. The process appears to be T-cell mediated, but antibodies directed to hair follicle structures also have been found with increased frequency in alopecia areata patients compared with control subjects. Using immunofluorescence, antibodies to anagen-phase hair follicles were found in as many as 90% of patients with alopecia areata compared with less than 37% of control subjects. The autoantibody response is heterogeneous and targets multiple structures of the anagen-phase hair follicle. The outer root sheath is the structure targeted most frequently, followed by the inner root sheath, the matrix, and the hair shaft. Whether these antibodies play a direct role in the pathogenesis or whether they are an epiphenomenon is not known. Histologically, lesional biopsy findings of alopecia areata show a perifollicular lymphocytic infiltrate around anagen-phase hair follicles. The infiltrate consists mostly of T-helper cells and, to a lesser extent, T-suppressor cells. CD4+ and CD8+ lymphocytes likely play a prominent role because the depletion of these T-cell subtypes results in complete or partial regrowth of hair in the Dundee experimental bald rat (DEBR) model of alopecia areata. The animals subsequently lose hair again once the T-cell population is replete. The fact that not all animals experience complete regrowth suggests that other mechanisms likely are involved. Total numbers of circulating T lymphocytes have been reported at both decreased and normal levels. Studies in humans also reinforce the hypothesis of autoimmunity. Studies have shown that hair regrows when affected scalp is transplanted onto SCID (severe combined immunodeficiency) mice that are devoid of immune cells. Autologous T lymphocytes isolated from an affected scalp were cultured with hair follicle homogenates and autologous antigen-presenting cells. Following initial regrowth, injection of the T lymphocytes into the grafts resulted in loss of regrown hairs. Injections of autologous T lymphocytes that were not cultured with follicle homogenates did not trigger hair loss. A similar experiment on nude (congenitally athymic) mice failed to trigger hair loss in regrown patches of alopecia areata after serum from affected patients was injected intravenously into the mice. However, the same study showed that mice injected with alopecia areata serum showed an increased deposition of immunoglobulin and complement in hair follicles of both grafted and nongrafted skin compared with mice injected with control serum, which showed no deposition. In addition, research has shown that alopecia areata can be induced using transfer of grafts from alopecia areata–affected mice onto normal mice. Transfer of grafts from normal mice to alopecia areata–affected mice similarly resulted in hair loss in the grafts. Clinical evidence favoring autoimmunity suggests that alopecia areata is associated with other autoimmune conditions, the most significant of which are thyroid diseases and vitiligo (see History). In conclusion, the beneficial effect of T-cell subtype depletion on hair growth, the detection of autoantibodies, the ability to transfer alopecia areata from affected animals to nonaffected animals, and the induction of remission by grafting affected areas onto immunosuppressed animals are evidence in favor of an autoimmune phenomenon. Certain factors within the hair follicles, and possibly in the surrounding milieu, trigger an autoimmune reaction. Some evidence suggests a melanocytic target within the hair follicle. Adding or subtracting immunologic factors profoundly modifies the outcome of hair growth. Genetics 2 Falling Hair Problems & Probable cure… 6 January 2011 Many factors favor a genetic predisposition for alopecia areata. The frequency of positive family history for alopecia areata in affected patients has been estimated to be 10-20% compared with 1.7% in control subjects.[1 ]The incidence is higher in patients with more severe disease (16-18%) compared with patients with localized alopecia areata (7-13%). Reports of alopecia areata occurring in twins also are of interest. No correlation has been found between the degree of involvement of alopecia areata and the type of alopecia areata seen in relatives. Several genes have been studied and a large amount of research has focused on human leukocyte antigen. Two studies demonstrated that human leukocyte antigen DQ3 (DQB1*03) was found in more than 80% of patients with alopecia areata, which suggests that it can be a marker for general susceptibility to alopecia areata. The studies also found that human leukocyte antigen DQ7 (DQB1*0301) and human leukocyte antigen DR4 (DRB1*0401) were present significantly more in patients with alopecia totalis and alopecia universalis. [2,3,4 ] Another gene of interest is the interleukin 1 receptor antagonist gene, which may correlate with disease severity. Finally, the high association of Down syndrome with alopecia areata suggests involvement of a gene located on chromosome 21. In summary, genetic factors likely play an important role in determining susceptibility and disease severity. Alopecia areata is likely to be the result of polygenic defects rather than a single gene defect. The role of environmental factors in initiating or triggering the condition is yet to be determined. Cytokines Interleukin 1 and tumor necrosis factor were shown to be potent inhibitors of hair growth in vitro. Subsequent microscopic examination of these cultured hair follicles showed morphologic changes similar to those seen in alopecia areata. Innervation and vasculature Another area of interest concerns the modification of perifollicular nerves. The fact that patients with alopecia areata occasionally report itching or pain on affected areas raises the possibility of alterations in the peripheral nervous system. Circulating levels of the neuropeptide calcitonin gene-related peptide (CGRP) were decreased in 3 patients with alopecia areata compared with control subjects. CGRP has multiple effects on the immune system, including chemotaxis and inhibition of Langerhans cell antigen presentation and inhibition of mitogen-stimulated T-lymphocyte proliferation. CGRP also increases vasodilatation and endothelial proliferation. Similar findings were reported in another study, in which decreased cutaneous levels of substance P and of CGRP but not of vasoactive intestinal polypeptide were found in scalp biopsy specimens. The study also noted a lower basal blood flow and greater vasodilatation following intradermal CGRP injection in patients with alopecia areata compared with control subjects. More studies are needed to shed light on the significance of these findings. Viral etiology Other hypotheses have been proposed to explain the pathophysiology of alopecia areata, but more evidence is needed to support them. Alopecia areata was believed to possibly have an infectious origin, but no microbial agent has been isolated consistently in patients. Many efforts have been made to isolate cytomegalovirus, but most studies have been negative. [5 ] 3 Falling Hair Problems & Probable cure… 6 January 2011 FREQUENCY UNITED STATES Prevalence in the general population is 0.1-0.2%. The lifetime risk of developing alopecia areata is estimated to be 1.7%. Alopecia areata is responsible for 0.7-3% of patients seen by dermatologists. [6,7 ] INTERNATIONAL Worldwide prevalence of alopecia areata is the same as that in the United States. MORTALITY/MORBIDITY Alopecia areata is a benign condition and most patients are asymptomatic; however, it can cause emotional and psychosocial distress in affected individuals. Self-consciousness concerning personal appearance can become important. Openly addressing these issues with patients is important in helping them cope with the condition. RACE All races are affected equally by alopecia areata; no increase in prevalence has been found in a particular ethnic group. SEX Data concerning the sex ratio for alopecia areata vary slightly in the literature. In one study including 736 patients, a male-to-female ratio of 1:1 was reported.[8 ]In another study on a smaller number of patients, a slight female preponderance was seen. AGE Alopecia areata can occur at any age from birth to the late decades of life. Congenital cases have been reported. Peak incidence appears to occur from age 15-29 years. As many as 44% of people with alopecia areata have onset at younger than 20 years. Onset in patients older than 40 years is seen in less than 30% of patients with alopecia areata. CLINICAL HISTORY The natural history of alopecia areata is unpredictable. Extreme variations in duration and extent of the disease occur from patient to patient. Alopecia areata most often is asymptomatic, but some patients (14%) experience a burning sensation or pruritus in the affected area. The condition usually is localized when it first appears. Of patients with alopecia areata, 80% have only a single patch, 12.5% have 2 patches, and 7.7% have multiple patches. No correlation exists between the number of patches at onset and subsequent severity. Alopecia areata most often affects the scalp (66.8-95%); 4 Falling Hair Problems & Probable cure… 6 January 2011 however, it can affect any hair-bearing area. The beard is affected in 28% (males; see first image below), eyebrows in 3.8%, and extremities in 1.3% of patients (see second image below). More than one area can be affected at once. ALOPECIA AREATA AFFECTING THE BEARD. 5 Falling Hair Problems & Probable cure… 6 January 2011 ALOPECIA AREATA AFFECTING THE ARMS. Localized alopecia areata: Episodes of localized (<50% involvement) patchy alopecia areata usually are self-limited; spontaneous regrowth occurs in most patients within a few months, with or without treatment. Extensive alopecia areata: Extensive (>50% involvement) forms of alopecia areata are less common. Alopecia totalis or alopecia universalis are reported to occur at some point in 7% of patients; alopecia areata involving more than 40% hair loss is seen in 11%. The proportion of patients with alopecia totalis appears to decrease with every decade of life. o In 30% of patients with alopecia totalis, complete hair loss occurred within 6 months after onset of disease. Sharma et al[9 ]reported a mean progression period to alopecia totalis of 4 months after onset. The natural evolution of alopecia totalis is unpredictable, but recurrences of alopecia areata (not necessarily alopecia totalis) are expected. o In a study involving 736 patients,[8 ]the relapse rate was 90% over 5 years. One percent of children and 10% of adults can experience long-lasting regrowth. Fortyfour percent of children and 34% of adults experience a significant period of normal or near-normal hair growth. Twenty-two percent of children and 34% of adults do not experience regrowth. Associated conditions: Because some of the entities associated with alopecia areata occur uncommonly in the general population, a large number of patients with alopecia areata need to be examined to confirm whether an increased prevalence of these conditions exists among patients with alopecia areata. Unfortunately, most studies are performed on small groups; therefore, the data should be interpreted carefully. 6 Falling Hair Problems & Probable cure… 6 January 2011 o Atopic dermatitis is seen in 9-26% of patients with alopecia areata. In the general population, the prevalence of atopic dermatitis in children in temperate developed countries varies from 5-20%. In adults, the prevalence decreases to 2-10%. Some authors have found atopy to be a poor prognostic factor for alopecia areata. o Vitiligo is seen with an incidence varying from 1.8-3% compared with 0.3% in control subjects. Also see Vitiligo. o Clinically evident thyroid disease was found in 0.85% of 1700 patients with alopecia areata.[10 ]The prevalence of thyroid disease determined on a clinical or laboratory basis varies among studies from 0.85-14.7%. The incidence of thyroid disease in control subjects is estimated to be 0.17-2%. The presence of microsomal antibodies is found in 3.3-16% of patients. Antibodies can be found with or without signs or symptoms of thyroid disease, but patients with positive autoantibodies have a higher incidence of functional abnormalities found on thyroid-releasing hormone tests (26% vs 2.8%). The incidence of thyroid microsomal and thyroglobulin antibodies in control subjects is 7%. Other studies have not supported these results. A study in 100 patients with alopecia areata failed to find an increased incidence of circulating autoantibodies, including mitochondrial and thyroglobulin antibodies. o Collagen-vascular diseases have been found in 0.6-2% of patients with alopecia areata, while the incidence in control subjects is 0.17%. The incidence of alopecia areata in 39 patients with lupus erythematous was 10% in a study by Werth et al,[11 ] in contrast to 0.42% of general dermatologic patients. o Diabetes mellitus was found to be more common in control subjects (1.4%) than in patients with alopecia areata (0.4%).[12 ]The occurrence of alopecia areata may protect against the appearance of type I diabetes mellitus. However, the incidence of type I diabetes mellitus was significantly higher in relatives of patients with alopecia areata compared with the general population. o Alopecia areata is seen in 6-8.8% of patients with Down syndrome, but only 0.1% of patients with alopecia areata have Down syndrome. The high frequency of alopecia areata in patients with Down syndrome suggests that a genetic linkage for alopecia areata may exist on chromosome 21. o Anxiety, personality disorders, depression, and paranoid disorders are seen with increased prevalence varying from 17-22% of patients, and the lifetime prevalence of psychiatric disorders is estimated to be 74% in patients with alopecia areata. Psychiatric problems are seen in both children and adults. No association has been made between the severity of the psychiatric disorder and that of alopecia areata. o Stressful life events within the 6-month period preceding episodes of alopecia areata were significantly higher in patients with alopecia areata compared with patients with androgenetic alopecia or tinea capitis. [13 ]Major stress factors (eg, death in family) were reported in 12% of patients. o Others associations in some studies include pernicious anemia, myasthenia gravis, ulcerative colitis, lichen planus, and Candida endocrinopathy syndrome. Precipitating factors: A precipitating factor can be found in 15.1% of patients with alopecia areata. Major life events, febrile illnesses, drugs, pregnancy, trauma, and many other events have been reported, but no clear conclusions can be drawn. Despite these findings, most patients with alopecia areata do not report a triggering factor preceding episodes of hair loss. PHYSICAL The presence of smooth, slightly erythematous (peach color) or normal-colored alopecic patches is characteristic. The presence of exclamation point hairs (ie, hairs tapered near proximal end) is pathognomonic but is not always found. A positive result from the pull test at the periphery of a plaque usually indicates that the disease is active, and further hair loss can be expected. Additionally, hair loss 7 Falling Hair Problems & Probable cure… 6 January 2011 on other hair-bearing areas also favors the diagnosis. The most common presentation is the appearance of one or many round-to-oval denuded patches. No epidermal changes are associated with the hair loss. Alopecia areata can be classified according to its pattern. Hair loss most often is localized and patchy (see image below). PATCHY ALOPECIA AREATA. A reticular pattern occurs when hair loss is more extensive and the patches coalesce. An ophiasis pattern occurs when the hair loss is localized to the sides and lower back of the scalp (see image below). 8 Falling Hair Problems & Probable cure… 6 January 2011 OPHIASIS PATTERN OF ALOPECIA AREATA. Conversely, sisaipho (ophiasis spelled backwards) pattern occurs when hair loss spares the sides and back of the head (see image below). 9 Falling Hair Problems & Probable cure… 6 January 2011 SISAIPHO PATTERN OF ALOPECIA AREATA. Alopecia totalis occurs with 100% hair loss on the scalp (see image below). 10 Falling Hair Problems & Probable cure… 6 January 2011 ALOPECIA TOTALIS. Alopecia universalis occurs with complete loss of hair on all hair-bearing areas. Alopecia areata usually is focal; however, it can be diffuse, thereby mimicking telogen effluvium (TE) or the type of androgenetic alopecia seen in women (see image below). 11 Falling Hair Problems & Probable cure… 6 January 2011 DIFFUSE ALOPECIA AREATA. See also Androgenetic Alopecia and Telogen Effluvium. Dermoscopy o Dermoscopic findings have been reported to be helpful in the diagnosis of difficult cases of alopecia areata. o The presence of yellow dots seems to be a specific feature of alopecia areata and has been reported to be present in 95% of patients, regardless of their disease stages. Following histopathological correlation, these yellow dots represent degenerated follicular keratinocytes and sebum contained within the ostium of hair follicles. Although occasionally seen in advanced male-pattern hair loss, yellow dots are not seen in cases of female-pattern hair loss, scaring alopecia, or telogen effluvium. o Other dermoscopic signs reported include black dots, tapering hairs, broken hairs, and clustered short vellus hairs. Nail involvement o Nail involvement is found in 6.8-49.4% of patients and most commonly is seen in patients with severe forms of alopecia areata. o Pitting is the most common finding. o Several other abnormalities have been reported (eg, trachyonychia, Beau lines, onychorrhexis, onychomadesis, koilonychia, leukonychia, red lunulae). o Fingernails predominantly are affected. 12 Falling Hair Problems & Probable cure… 6 January 2011 CAUSES The true cause of alopecia areata remains unknown. The exact role of possible factors needs to be clarified (see Pathophysiology). No known risk factors exist for alopecia areata, except a positive family history. The exact role of stressful events remains unclear, but they most likely trigger a condition already present in susceptible individuals, rather than acting as the true primary cause. DIFFERENTIAL DIAGNOSES Androgenetic Alopecia Pseudopelade, Brocq Syphilis Telogen Effluvium Tinea Capitis Trichotillomania OTHER PROBLEMS TO BE CONSIDERED Trichotillomania: Alopecic patches have unusual shapes and sizes and show broken hairs; no inflammation or epidermal change occurs. A scalp biopsy can be helpful if the diagnosis is difficult clinically. Tinea capitis: The diagnosis is suggested by erythema, scaling, and crusting locally on the scalp. Scarring alopecia and posttraumatic alopecia: These can be differentiated by the absence of follicular ostia or some degree of atrophy. Syphilis: Syphilis rarely is seen but should be suspected in patients at high risk or with other signs or symptoms. Telogen effluvium and androgenetic alopecia: Exclude these when hair loss is diffuse. In androgenetic alopecia, hair loss is patterned and usually is slowly progressive rather than acute. Differentiating telogen effluvium from diffuse alopecia areata is difficult in the absence of an obvious precipitating factor that can result in telogen effluvium. Noting hair loss on other hair-bearing areas can be helpful and favors a diagnosis of alopecia areata. WORKUP PROCEDURES Diagnosis usually can be made on clinical grounds; a scalp biopsy seldom is needed, but it can be helpful when the clinical diagnosis is less certain. HISTOLOGIC FINDINGS A histologic diagnosis of alopecia areata can be made when characteristic features are present. Horizontal sections usually are preferred to vertical sections because they allow examination of multiple hair follicles at different levels. 13 Falling Hair Problems & Probable cure… 6 January 2011 The most characteristic feature is a peribulbar lymphocytic infiltrate, which is described as appearing similar to a swarm of bees. The infiltrate often is sparse and usually involves only a few of the affected hairs in a biopsy specimen. Occasionally, no inflammation is found, which can result in diagnostic difficulties. A significant decrease in terminal hairs is associated with an increase in vellus hairs, with a ratio of 1.1:1 (normal is 7:1). Other helpful findings include pigment incontinence in the hair bulb and follicular stellae. A shift occurs in the anagen-to-telogen ratio, which is not specific. The normal ratio is approximately 90% anagen phase to 10% telogen phase hair follicles; in alopecia areata, 73% of hairs are found to be in the anagen phase and 27% in the telogen phase. In long-standing cases of alopecia areata, the percentage of telogen-phase hairs can approach 100%. Degenerative changes of the hair matrix can be found but are uncommon. Eosinophils may be present in fibrous tracts and near hair bulbs. TREATMENT MEDICAL CARE See the treatment algorithm below. 14 Falling Hair Problems & Probable cure… 6 January 2011 TREATMENT ALGORITHM FOR ALOPECIA AREATA. 15 Falling Hair Problems & Probable cure… 6 January 2011 Treatment is not mandatory because the condition is benign, and spontaneous remissions and recurrences are common. Treatments used are believed to stimulate hair growth, but no evidence indicates they can influence the ultimate natural course of alopecia areata. Treatment modalities usually are considered first according to the extent of hair loss and the patient's age. Assessment of the efficacy of a treatment must be considered with care because the condition is highly unpredictable in presentation, evolution, and response to treatment. Little data exist regarding the natural evolution of the condition. For example, in patients with less than 40% scalp involvement, a study showed no benefit with treatment (minoxidil 1% and topical immunotherapy) over placebo. [14 ] The high spontaneous remission rate makes clearly assessing the true efficacy of a therapy difficult unless appropriate controls with placebo treatment are studied. For patients with extensive alopecia areata (>40% hair loss), little data exist on the natural evolution. The rate of spontaneous remission appears to be less than in patients with less than 40% involvement. Vestey and Savin [15 ]reviewed 50 patients with extensive alopecia areata. Of the 50 patients, 24% experienced spontaneous complete or nearly complete regrowth at some stage during the observation period of 3-3.5 years. The relapse rate is high in patients with severe forms of alopecia areata. Patients with alopecia totalis or alopecia universalis usually have a poorer prognosis, and treatment failure is seen in most patients with any therapy. Because alopecia areata is believed to be an autoimmune condition, different immunomodulators have been used to treat this condition. Additional treatment options for alopecia areata include minoxidil and other treatment modalities. Topical treatments Corticosteroids Corticosteroid therapies can include intralesional injections or topical application. For intralesional steroids, few studies are available regarding efficacy; however, they are used widely in the treatment of alopecia areata. o Intralesional steroids are the first-line treatment in localized conditions. o In a study including 84 patients, regrowth on treated areas was present in 92% of patients with patchy alopecia areata and 61% of patients with alopecia totalis. Regrowth persisted 3 months after treatment in 71% of patients with patchy alopecia areata and 28% of patients with alopecia totalis. Regrowth usually is seen within 4-6 weeks in responsive patients. Patients with rapidly progressive, extensive, or long-standing alopecia areata tend to respond poorly. o Another study showed regrowth in most patients (480) treated with intralesional steroids, except in 2 patients with alopecia universalis. o Hair growth may persist for 6-9 months after a single injection. o Injections are administered intradermally using a 3-mL syringe and a 30-gauge needle. o Triamcinolone acetonide (Kenalog) is used most commonly; concentrations vary from 2.5-10 mg/mL. The lowest concentration is used on the face. A concentration of 5 mg/mL is usually sufficient on the scalp. 16 Falling Hair Problems & Probable cure… 6 January 2011 o Less than 0.1 mL is injected per site, and injections are spread out to cover the affected areas (approximately 1 cm between injection sites; see image below). o CORTICOSTEROID INJECTION. o Adverse effects mostly include pain during injection and minimal transient atrophy (10%). The presence of atrophy should prompt a reduction in the triamcinolone acetonide concentration and avoidance of the atrophic site. o Injections are administered every 4-6 weeks. o Although intralesional injections of triamcinolone acetonide are usually recommended for alopecia areata with less than 50% involvement, a report showed that 6 of 10 patients had regrowth.[16 ]Although injections may work in extensive alopecia areata, results are unlikely if no response is observed at 6 months (personal observation). For topical steroids, again, few studies have been performed regarding efficacy in the treatment of alopecia areata; they can however be useful, especially in children who cannot tolerate injections. o Fluocinolone acetonide cream 0.2% (Synalar HP) twice per day induced a satisfactory-to-excellent response in 61% of patients, which was maintained in 71% of patients. Children younger than 10 years responded better, as did patients with a duration of hair loss of less than 1 year. o Betamethasone dipropionate cream 0.05% (Diprosone) showed similar efficacy. o A 2005 study by Tosti et al[17 ]in patients with alopecia totalis or alopecia universalis showed that the use of 2.5 g of clobetasol propionate under occlusion with a plastic 17 Falling Hair Problems & Probable cure… 6 January 2011 o o o film 6 d/wk for 6 months induced regrowth in 8 (28.5%) of 28 patients. Regrowth was seen 6-14 weeks after the onset of therapy. Regrowth was maintained for at least 6 months after cessation of therapy in 5 (62.5%) of 8 patients. Even though only 17.8% of patients showed long-term benefits from that treatment, it should be kept in mind that the study was performed in a subgroup of patients that is usually refractory to treatment. Treatment must be continued for a minimum of 3 months before regrowth can be expected, and maintenance therapy often is necessary. Despite these data, the authors do not believe that monotherapy with a topical steroid has been of great benefit in the authors' practice. The most common adverse effect is local folliculitis, which appears after a few weeks of treatment. Telangiectases and local atrophy also have been reported. No systemic adverse effects have been reported. Immunotherapy Topical immunotherapy[18 ]is defined as the induction and periodic elicitation of an allergic contact dermatitis by topical application of potent contact allergens. Commonly used agents for immunotherapy include squaric acid dibutylester (SADBE) and diphencyprone (DPCP).[19 ]These 2 sensitizers are not present in the natural or industrial environment. Dinitrochlorobenzene (DNCB) has become less popular as a result of reports that it is mutagenic in the Ames assay (a bacterial assay). No rigorous toxicologic and pharmacologic studies have been performed on the use of these agents in humans. Although DPCP and SADBE have not been found mutagenic in the Ames assay, neither is approved by the US Food and Drug Administration, and unknowns still exist concerning their safety profiles. No contaminants have been found in SADBE. Acetone solutions and alcohol solutions of SADBE are equally stable for 2 months under storage conditions. DPCP occasionally can contain mutagenic contaminants; therefore, it should be screened periodically to ensure purity. No formal data are available on DPCP regarding its longevity in solution. Cosmetically acceptable regrowth with topical immunotherapy rates in patients with severe alopecia areata (>50% involvement) varies from 22-68%. Most studies have a success rate of [20 ] 30-50%. Wiseman et al retrospectively reported the results of a large cohort of 148 consecutive patients treated with DPCP. o Their analysis showed that the cumulative patient response at 32 months was 77.9%. o The response rate varied with the extent of the alopecia. Cosmetically acceptable regrowth was seen in 17.4% of patients with alopecia totalis or alopecia universalis, 60.3% in patients with 75-99% hair loss, 88.1% in patients with 50-74% hair loss, and 100% regrowth in those with 25-49% hair loss. o Age at onset was also a significant variable, with older age at onset leading to a better prognosis. A lag period of 3 months was usually present between the onset of therapy and the presence of regrowth. o The median time to achieve significant regrowth was 12.2 months. Some patients showed regrowth on the treated side after 18 months of therapy. o No benefit is achieved with continuing therapy after 24 months in the absence of regrowth. o The relapse rate after reaching significant regrowth was 62.6%. In a report of a 5-year experience with the use of DPCP, 97 subjects received continued therapy with DPCP. A response rate of greater than 75% was seen in 15% at 6 months, 49% at 12 months, 53% at 18 months, and 56% at 24 months. The only variable that seemed to 18 Falling Hair Problems & Probable cure… 6 January 2011 affect response to treatment was the baseline extent of the alopecia areata. A greater than 75% response rate was seen in 100% of patients with 25-49% hair loss at baseline, 77% of those with 50-74% loss at baseline, 54% of those with 75-99% loss at baseline, 50% of alopecia totalis patients, and 41% of alopecia universalis patients demonstrated a response. Maintenance treatment (once every 1-4 wk) appeared to reduce the risk of relapse (>25% hair loss). Only 18% of patients experienced relapse on maintenance therapy, compared with 57% in those who discontinued treatment[21 ] The type of alopecia areata before treatment, duration of the disease, and the presence of nail changes were found to predict a lower response to treatment. Age at onset and sex of the patient do not appear to influence the prognosis. Controversy exists concerning whether atopy is an adverse prognosis factor. Topical immunotherapy has been used for almost 20 years; no serious adverse effects have been reported. The most common side effect, which is desired, is a mild contact dermatitis (redness, scaling, itching). Adverse effects include cervical lymphadenopathy and pigment changes. Vitiligo developed on the application site in 6.7-7.5% of patients. Transient leukoderma on a distant untreated area has been reported. Of patients who develop vitiligo, 31% (4 of 13) had a history of vitiligo. Only 0.75% of patients developed hyperpigmentation. Confetti-type dyschromia (ie, hyperpigmentation, hypopigmentation) has been described as an adverse effect of DPCP treatment and occurred in 1.6% of 243 patients treated. Less common adverse effects include erythema multiforme–like eruptions and urticaria, which were reported in 3 patients treated with DPCP. The mechanism of action of topical immunotherapy is unknown. Antigenic competition has been hypothesized. That is, the introduction of a second antigen can initiate a new infiltrate containing T-suppressor cells and suppressor macrophages that may modify the preexisting infiltrate and allow regrowth. Because topical immunotherapy involves the production of contact sensitivity in a previously naive patient, it is best to seek approval for the treatment by the ethics review board and to have the patient sign an informed consent. Both SADBE and DPCP appear to be equally effective. Acetone-based solutions usually are preferred because they evaporate quickly, allowing patients to wear a hat or wig immediately after treatment. Quick drying also decreases the chances of dissemination to other body parts by contact. Treatment is provided weekly. The patient first is sensitized directly on the scalp with a 2% concentration on a small area (2 cm). The following week, a low concentration (0.0001%) is applied. The concentration is increased slowly every week as needed until a mild tolerable allergic contact dermatitis is elicited. Many concentrations are available that achieve this goal. Treating only half of the head allows the physician to use the untreated half as a control. Once regrowth occurs on the treated half, treatment can be applied to the entire scalp. If regrowth initially occurs on both sides, spontaneous remission is likely, although treatment cannot be excluded as the cause. Avoid severe contact dermatitis. Patients are advised to avoid light exposure on the scalp for 48 hours because light degrades the chemical. Patients also are advised not to wash the scalp for 48 hours. Initial regrowth may be seen at weeks 12-24. Once cosmetically acceptable regrowth is achieved, the treatment can be tapered gradually. Almost all patients relapse if the treatment is discontinued, and maintenance treatment is needed. Anthralin The efficacy of anthralin was assessed in 3 studies, which unfortunately were uncontrolled. 19 Falling Hair Problems & Probable cure… 6 January 2011 Both short-contact and overnight treatments have been used. Anthralin concentrations varied from 0.2-1%. [22 ] A 2004 study by Tang et al showed no benefit in using anthralin. Other studies showed a response rate of 20-75%, respectively, for patchy alopecia areata and a 25% response rate for alopecia totalis. The mean time to response was 11 weeks, and the mean time to cosmetic response was 23 weeks. Anthralin was used by Tang et al in balding C3H/HeJ mice, which is one animal model for alopecia areata. Half the body was treated with anthralin 0.2%, while the other side was treated with the vehicle ointment. Regrowth was seen on the treated side in 64% of mice after 10 weeks. Four mice had almost complete regrowth. The untreated side showed either no regrowth or continued hair loss. Cytokine studies performed with an RNase protection assay showed that tumor necrosis factor-alpha and beta were inhibited in mice that responded to treatment. Most patients experienced irritant contact dermatitis. Whether the dermatitis is necessary for efficacy remains under debate. Cosmetically acceptable regrowth was maintained during therapy in 71% of responders. No correlation exists between duration of the current episode and response to treatment. Adverse effects include pruritus, erythema, scaling folliculitis, local pyoderma, and regional lymphadenopathy. Withholding treatment for a few days results in rapid disappearance of adverse effects. Treatment then can be reinstituted, but anthralin should be left on for shorter periods. Staining of clothes and skin can be a concern. The mechanism of action of anthralin is unknown. Most likely, it creates inflammation by generating free radicals, which have antiproliferative and immunosuppressive actions. Minoxidil Minoxidil appears to be effective in the treatment of alopecia areata in patients with extensive disease (50-99% hair loss). Response rates in that group vary from 8-45%. Minoxidil was of little benefit in patients with alopecia totalis or alopecia universalis. The 5% solution appears to be more effective. No more than 25 drops are applied twice per day regardless of the extent of the affected area. Initial regrowth can be seen within 12 weeks, but continued application is needed to achieve cosmetically acceptable regrowth. Minoxidil usually is well tolerated. Adverse effects include distant hypertrichosis (5%) and irritation (7%). The exact mechanism of action of minoxidil remains unclear. Minoxidil does not appear to have either a hormonal or an immunosuppressant effect. Minoxidil most likely has a direct mitogenic effect on epidermal cells, both in vitro and in vivo. Anagen-phase hair bulbs plucked from men applying minoxidil showed a significant increase in proliferation index as measured by DNA flow cytometry. Minoxidil also has been shown to prolong the survival time of keratinocytes in vitro. Finally, minoxidil may oppose intracellular calcium entry. Calcium influx normally enhances epidermal growth factors to inhibit hair growth. Minoxidil is converted to minoxidil sulfate, which is a potassium channel agonist and enhances potassium ion permeability, thus opposing the entry of calcium into cells. Local vasodilatation does not appear to play a primary role in hair growth associated with minoxidil. Systemic treatments Psoralen plus UV-A 20 Falling Hair Problems & Probable cure… 6 January 2011 Many studies have been performed regarding the efficacy of psoralen plus UV-A (PUVA) in the treatment of alopecia areata, and the initial response rate varies from 20-73%. The relapse rate, unfortunately, is high (50-88%). Most patients relapse within a few months (mean 4-8 mo) after treatment is stopped. Both systemic and topical PUVA therapies have been used. The number of treatments required for regrowth varies, but 20-40 treatments usually are sufficient in most cases. A younger age at onset, a longer duration of disease, and the presence of alopecia totalis or alopecia universalis appear to indicate a poorer outcome. [23 ] o Taylor and Hawk published 10 years of experience with PUVA. The initial response rate (>90% regrowth) was comparable to other studies and was 43.8% for partial alopecia areata and 50% for alopecia totalis and alopecia universalis. However, after excluding patients with vellus hair regrowth and patients who relapsed rapidly in the follow-up period (approximately 4 mo), they found the success rate to be, at best, 6.3% for partial alopecia areata and 12.5% for alopecia totalis and alopecia universalis. They concluded that PUVA generally is not an effective long-term treatment for alopecia areata. o PUVA is a relatively safe treatment modality; adverse effects include burning and, possibly, an increased risk of skin cancer. Prednisone The use of systemic steroids for the treatment of alopecia areata is sometimes justifiable, but hair loss frequently follows discontinuation of the medication and benefits must be carefully weighed against long-term risks. Some authors support a beneficial role of systemic steroids in halting the progression of alopecia areata,[24 ]but many others have had poor results with this form of therapy. The rate of regrowth varies greatly (27-89%), and many dose regimens have been used in these studies. Although the initial regrowth appears promising, the prednisone dose necessary to maintain cosmetic growth usually must be high enough that adverse effects are inevitable, and most patients relapse after therapy is discontinued. Some benefit was shown using minoxidil 2% solution applied twice per day following a 6week taper of prednisone, but the relapse rate remained at a minimum of 50% at 4 months in the treated group. Adverse effects from systemic therapy were common in these reports and included diabetes, weight gain, hypertension, psychological changes, osteoporosis, suppression of the adrenocorticotropic axes, striae, acne, hypertrichosis, and purpura. Systemic steroids most likely are effective via their immunosuppressive effects. An initial benefit may occur by using systemic prednisone in some patients, but the relapse rate is high, and it does not appear to alter the course of the condition. Systemic prednisone is not an agent of choice for alopecia areata because of the adverse effects associated with both short- and long-term treatment. Cyclosporine Cyclosporine has been used both topically and systemically in the treatment of alopecia areata. Topical cyclosporine has not proven to be effective in severe alopecia areata because no patient (0 of 10) showed benefit with application of a 10% cyclosporin A (CsA) solution twice per day for 12 months. 21 Falling Hair Problems & Probable cure… 6 January 2011 Another study of 14 patients using a 5% solution of cyclosporine twice per day for 4-6 months reported vellus growth in 3 of 14 patients and normal hair growth in 3 patients with patchy alopecia areata. No regrowth was seen in 8 of the patients. Neither study showed systemic absorption of CsA, and routine blood examination showed only a transient increase of hepatic enzymes in 1 patient. Oral cyclosporine was effective in the DEBR model for alopecia areata. All rats had a full pelage by 5 weeks of treatment with 10 mg/kg/d, 5 d/wk for 7 weeks. Studies in humans also have proven efficacy with doses of 6 mg/kg/d for 3 months in 6 patients. All patients experienced regrowth, and cosmetically acceptable regrowth was seen in 3 of 6 patients. Unfortunately, all patients relapsed within 3 months of discontinuation of cyclosporine. No evidence indicates that CsA can prevent hair loss during an active episode because reports have described patients taking CsA who developed alopecia areata while they were under treatment for unrelated conditions. The mechanism of action of cyclosporine remains unclear. It may act through its immunosuppressive effect, because, in patients who regrew hair, clearance of immune cells from the hair follicles and alteration in the balance of regulatory lymphocytes occurred (ie, decrease of the CD4/CD8 ratio). Cyclosporine causes hypertrichosis in patients treated for conditions unrelated to hair loss. The mechanism by which cyclosporine stimulates hair growth remains unknown. In conclusion, topical cyclosporine has shown limited efficacy. Although systemic CsA appears to be effective in alopecia areata, the adverse effect profile, the recurrence rate after treatment discontinuation, and thus, the inability to produce long-term remissions, make CsA unattractive for the treatment of alopecia areata. Tacrolimus Regrowth was shown on the application site of topical tacrolimus in 2 studies using the DEBR model. Oral tacrolimus was ineffective. No benefit was shown in the use of topical tacrolimus for alopecia areata in a small 2005 study by Price et al that included 11 patients. [25 ] Interferon A study of 11 patients with alopecia areata ranging from patchy alopecia areata to alopecia universalis showed no benefit using intralesional interferon alfa-2 (1.5 million IU, 3 times per wk for 3 wk). Dapsone Dapsone at 50 mg twice per day was used in a 6-month, double-blind, placebo-controlled study. Of patients in the study, 54% (7 of 13) withdrew from the dapsone group because of adverse effects such as malaise. Of the remaining 6 patients, 3 experienced generalized growth of terminal hair, compared with 4 (4 of 13) patients in the placebo group, who experienced only sparse patchy regrowth of vellus hair. The authors concluded that although dapsone showed some efficacy, the high incidence of adverse effects rendered it unacceptable. Another study showed a rate of success comparable to the occurrence of spontaneous regrowth reported in the literature. Methotrexate Joly[26 ]reported 22 patients with long-standing, severe alopecia areata who responded well to methotrexate, with or without systemic corticosteroids. Although the results from that study are surprisingly good, a more standardized study involving more patients is needed because other dermatologists have not had such good efficacy with methotrexate. 22 Falling Hair Problems & Probable cure… 6 January 2011 Other treatment modalities Many other modalities have been reported to have variable response rates in small studies. These include latanoprost,[27 ]nitrogen mustard, massage and relaxation, isoprinosine, acupuncture, and aromatherapy, among others. The efficacy of these treatments needs to be demonstrated in larger, placebo-controlled trials before they can be recommended. Biological agents The majority of studies, including prospective, randomized placebo controlled studies [28,29 ]and case reports published in the last few years regarding the use of biologic agents (including adalimumab, alefacept, etanercept and infliximab) in the treatment of alopecia areata did not show efficacy, and some patients developed alopecia areata while under treatment with biologic agents for other conditions. Nonpharmacologic methods A systematic MEDLINE search could not find any study with sufficient validity to provide scientific evidence of benefit with complementary and alternative medicine therapies for alopecia areata. [30 ] A study on hypnosis for refractory alopecia areata did not show efficacy of regrowth, but it did show that hypnosis can improve depression, anxiety, and quality of life in affected patients. [31 ] Cosmetic treatments for patients with alopecia areata include dermatography and hairpieces. Dermatography has been used to camouflage the eyebrows of patients with alopecia areata. Follow-up visits at 4 years showed that 30 of 39 of patients demonstrated excellent cosmetic results and 3 had good results. On average, 2-3 sessions lasting 1 hour each were required for each patient. No adverse effects were reported. Hairpieces are useful for patients with extensive disease and allow them to carry on their usual social life. Reassure patients about the natural look provided by hairpieces. SURGICAL CARE Surgical intervention has no role in the treatment of alopecia areata. MEDICATION Therapies most commonly include corticosteroid injections, corticosteroid creams, minoxidil, anthralin, topical immunotherapy, and phototherapy. The choice of one agent over the others depends on patient age (children do not always tolerate adverse effects), extent of condition (localized vs extensive), and the patient's personal preference. The University of California (San Francisco) and University of British Columbia have devised a treatment algorithm that can guide the physician in the treatment of alopecia areata (see image below). 23 Falling Hair Problems & Probable cure… 6 January 2011 TREATMENT ALGORITHM FOR ALOPECIA AREATA. 24 Falling Hair Problems & Probable cure… 6 January 2011 For patients younger than 10 years, options include corticosteroid creams, minoxidil, and anthralin. For adults with less than 50% scalp involvement, the first option usually is an intralesional corticosteroid, followed by corticosteroid cream, minoxidil, and anthralin. For adults with greater than 50% scalp involvement, topical immunotherapy and phototherapy are additional options. IMMUNOMODULATORS Because alopecia areata is believed to be an autoimmune condition, different immunomodulators have been used to treat the condition. Exact mechanism of action of topical immunotherapy is unknown. Antigenic competition was hypothesized (ie, introduction of a second antigen can initiate a new infiltrate containing T-suppressor cells and suppressor macrophages that may modify preexisting infiltrate and allow regrowth). Commonly used agents for immunotherapy include SADBE and DPCP. SQUARIC ACID DIBUTYLESTER AND DIPHENCYPRONE May modulate key factors of the immune system. DOSING ADULT First, sensitize patient directly on scalp using 2% concentration on small area (2 cm); the following wk, apply lowest concentration (0.0001%); slowly increase concentration each wk thereafter prn until mild tolerable allergic contact dermatitis is elicited. PEDIATRIC <12 years: Not established >12 years: Apply as in adults INTERACTIONS None reported. CONTRAINDICATIONS Documented hypersensitivity, documented anaphylaxis, pregnancy, breastfeeding PRECAUTIONS 25 Falling Hair Problems & Probable cure… 6 January 2011 PREGNANCY C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PRECAUTIONS Local common adverse effects include burning, itching, blistering, crusting, urticaria, eczema, and cervical lymphadenopathy; less common adverse effects include vitiligo, dyschromia in confetti, erythema multiforme–like eruptions, and urticaria CYCLOSPORINE (SANDIMMUNE, NEORAL) Used both topically and systemically for the treatment of alopecia areata. Topical cyclosporine has shown limited efficacy. Although systemic CsA appears to be effective in alopecia areata, the adverse effect profile, recurrence rate after treatment discontinuation, and inability to produce long-term remissions make CsA unattractive for the treatment of alopecia areata. Mechanism by which cyclosporine stimulates hair growth remains unknown. May act through its immunosuppressive effect because patients who regrew hair had clearance of immune cells from the hair follicles and alteration in the balance of regulatory lymphocytes (ie, decreased CD4/CD8 ratio). Causes hypertrichosis in patients treated for conditions unrelated to hair loss. DOSING ADULT Topical cyclosporine: Apply 5-10% formulations bid Systemic cyclosporine: 1-6 mg/kg/d PO in 2 divided doses PEDIATRIC Not established; see note in Contraindications INTERACTIONS Erythromycin, clarithromycin, azithromycin, norfloxacin ciprofloxacin, cephalosporins, doxycycline, ketoconazole, itraconazole, fluconazole, ritonavir, indinavir, saquinavir, nelfinavir, diltiazem, verapamil, nicardipine, cimetidine, methylprednisolone, dexamethasone, thiazides, furosemide, allopurinol, bromocriptine, danazol, amphotericin B, metoclopramide, oral contraceptive pills, warfarin, and grapefruit juice increase CsA levels Rifampin, rifabutin, nafcillin, carbamazepine, phenobarbital, phenytoin, valproate, octreotide, and ticlopidine decrease CsA levels Tobramycin, gentamicin, ketoconazole, azapropazone, TMP-SMZ, vancomycin, sulindac, amphotericin B, indomethacin, naproxen, cimetidine, ranitidine, diclofenac, tacrolimus, and melphalan 26 Falling Hair Problems & Probable cure… 6 January 2011 potentiate renal toxicity Because of decreased renal clearance, coadministration with digoxin may lead to digitalis toxicity, coadministration with lovastatin may lead to myositis, and coadministration with methylprednisolone or prednisolone may lead to convulsions; coadministration with ACE inhibitors, potassium supplements, and potassium-sparing diuretics increases risk of hyperkalemia CONTRAINDICATIONS Absolute: Significantly decreased renal function, uncontrolled hypertension, hypersensitivity, clinically cured or persistent malignancy (except nonmelanoma skin cancer) Relative: Age <18 or >64 (however, CsA at 5 mg/kg/d for 6 wk shown to be safe and effective for patients aged 2-16 y with severe atopic dermatitis), controlled hypertension, planning to receive a liveattenuated vaccine, active infection or evidence of immunodeficiency, concurrent phototherapy, coal tar, methotrexate (or other immunosuppressive agents), pregnancy or lactation, unreliable patient, severe hepatic dysfunction PRECAUTIONS PREGNANCY C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PRECAUTIONS Evaluate renal and liver function often by measuring BUN, serum creatinine, serum bilirubin, and liver enzyme levels; may increase risk of infection and lymphoma; reserve IV use for patients who cannot take PO METHOXSALEN (8-MOP, OXSORALEN) Inhibits mitosis by binding covalently to pyrimidine bases in DNA when photoactivated by UV-A. DOSING ADULT 0.6-0.8 mg/kg PO, 1-2 h prior to UV-A exposure; can be administered topically (cream, lotion, soak) Supplied as methoxsalen 10 mg cap (generic) or a 1% lotion (Oxsoralen lotion) for topical use PEDIATRIC Not established 27 Falling Hair Problems & Probable cure… 6 January 2011 INTERACTIONS Toxicity increases with phenothiazines, griseofulvin, nalidixic acid, tetracyclines, thiazides, or sulfanilamides; bacteriostatic soaps and organic staining dyes CONTRAINDICATIONS Documented hypersensitivity, history of melanoma or squamous cell carcinoma, photosensitive conditions (eg, lupus, porphyria), intolerance to heat, or claustrophobia, ingestion of photosensitizing drugs, hepatitic disease, arsenic therapy PRECAUTIONS PREGNANCY C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PRECAUTIONS Severe burns may occur from sunlight or UV-A if dose or treatment frequency exceeded; use only if response to other forms of therapy is inadequate; long-term use may increase risk of skin cancer ANTHRALIN (DRITHO-SCALP 0.5% CREAM, ANTHRA-DERM 1% CREAM, DRITHOCREME 1%, MICANOL 1% CREAM) Synthetic derivative of a tree bark extract. Mechanism of action in alopecia areata is unknown. Most likely creates inflammation by generating free radicals, which have antiproliferative and immunosuppressive actions. Both short-contact and overnight treatments have been used. High concentration (1-3%) is used for short-contact treatments. Lower concentrations (0.1-0.4%) are used for overnight treatments. Applications in excessive amounts may stain clothing. DOSING ADULT Apply sparingly to affected areas; usually, short-contact treatments last a few h (depending on level of cutaneous irritation), then wash off with soap and water; overnight treatments apply hs and wash off in morning PEDIATRIC Administer as in adults 28 Falling Hair Problems & Probable cure… 6 January 2011 INTERACTIONS Long-term corticosteroid treatment withdrawal may cause complications of rebound phenomenon (allow 1-wk interval between discontinuation of corticosteroids and initiation of anthralin therapy) CONTRAINDICATIONS Documented hypersensitivity, acutely or actively swollen psoriatic lesions PRECAUTIONS PREGNANCY C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PRECAUTIONS Caution in renal disease; avoid eye contact; if redness develops, discontinue application; adverse effects include pruritus, erythema, scaling folliculitis, local pyoderma, and regional lymphadenopathy; caution on irritated skin because most likely aggravates preexisting condition; may discolor skin to brown-orange color (temporary) GLUCOCORTICOIDS Have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli. Topical corticosteroids (including intralesional corticosteroids) are safe and easy to use. They are acceptable cosmetically and allow patients to wear hats or wigs shortly after application. They also are relatively inexpensive. While the usefulness of high-potency topical corticosteroids is under debate, they remain a good (painless) option in children. Intralesional steroids are first-line treatment in localized conditions. Oral prednisone usually is reserved for patients with rapidly progressive alopecia areata. The relapse rate is high, and the potential for multiple severe adverse effects when used long term limits its usefulness. CLOBETASOL PROPIONATE (TEMOVATE) Class I superpotent topical steroid. Suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction. Treatment should continue until cosmetically acceptable regrowth is achieved or for a minimum of 3-4 mo. 29 Falling Hair Problems & Probable cure… 6 January 2011 DOSING ADULT Apply bid for up to 2 wk; not to exceed 50 g/wk PEDIATRIC Not established INTERACTIONS None reported CONTRAINDICATIONS Documented hypersensitivity; viral or fungal skin infections PRECAUTIONS PREGNANCY C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PRECAUTIONS May suppress adrenal function in prolonged therapy; most common adverse effect is local folliculitis, which appears after few weeks of treatment; telangiectasias and local atrophy have been reported; dryness, burning, itching, and local irritation may occur; secondary infection is rare; no systemic adverse effects have been reported PREDNISONE (DELTASONE, METICORTEN, STERAPRED) Immunosuppressant occasionally used in rapidly progressive alopecia areata in an attempt to halt condition, but relapse rate is high. Use of systemic steroids for treatment of alopecia areata is under much debate. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. Many drug doses and regimens have been used in treatment of alopecia areata, but no formal recommendation exists. DOSING 30 Falling Hair Problems & Probable cure… 6 January 2011 ADULT <60 kg: Not established >60 kg: 40 mg PO for 1 wk, 35 mg PO for 1 wk, 30 mg PO for 1 wk, 25 mg PO for 1 wk, 20 mg PO for 3 d, 15 mg PO for 3 d, 10 mg PO for 3 d, and 5 mg PO for 3 d PEDIATRIC 4-5 mg/m2/d PO or 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve INTERACTIONS Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics CONTRAINDICATIONS Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connectivetissue infections, and fungal or tubercular skin infections; GI disease PRECAUTIONS PREGNANCY B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals PRECAUTIONS Abrupt discontinuation of glucocorticoids may cause adrenal crisis; adverse effects from systemic therapy are common and include diabetes, weight gain, hypertension, electrolyte and fluid imbalance, psychological changes, osteoporosis, suppression of adrenocorticotropic axes, striae, acne, hypertrichosis, and purpura; ocular or GI complaints, renal function impairment, immunosuppression, and avascular necrosis may occur TRIAMCINOLONE ACETONIDE SUSPENSION (KENALOG 10 MG/ML OR 40 MG/ML) In alopecia areata, intralesional triamcinolone is believed to suppress the immune system locally and thereby allow hair to regrow. Injections are administered with 3-mL syringe and 30-gauge needle intralesionally. Pediatric patients generally are less tolerant of intralesional injections because of local discomfort. 31 Falling Hair Problems & Probable cure… 6 January 2011 DOSING ADULT 2.5- to 5-mg/mL concentrations typically administered, injected intralesionally, spread out to cover affected areas (approximately 1 cm between injection sites) Alternatively, 60 mg IM followed by additional doses of 20-100 mg when symptoms recur PEDIATRIC Administer as in adults INTERACTIONS Coadministration with barbiturates, phenytoin, and rifampin decreases effects CONTRAINDICATIONS Coadministration with barbiturates, phenytoin, and rifampin decreases effects PRECAUTIONS PREGNANCY C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PRECAUTIONS Adverse effects include pain during injection and minimal transient atrophy (10%); rarely, atrophy is severe and permanent (avoid reinjecting area of denting to allow atrophy to revert); if large volume is injected per session, suppression of HPA axis may occur BETAMETHASONE DIPROPIONATE CREAM 0.05% (DIPROSONE) For inflammatory dermatosis responsive to steroids. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. DOSING ADULT 32 Falling Hair Problems & Probable cure… 6 January 2011 Apply thin film bid until response PEDIATRIC Administer as in adults INTERACTIONS Effects decrease with coadministration of barbiturates, phenytoin, or rifampin; dexamethasone decreases effect of salicylates and vaccines used for immunization CONTRAINDICATIONS Documented hypersensitivity; paronychia, cellulitis, impetigo, angular cheilitis, erythrasma, erysipelas, rosacea, perioral dermatitis, and acne PRECAUTIONS PREGNANCY C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PRECAUTIONS Not for use in skin with decreased circulation; can cause atrophy of groin, face, and axillae; if infection unresponsive to antibiotic treatment develops, discontinue until infection is controlled; do not use as monotherapy to treat widespread plaque psoriasis VASODILATORS Relax arteriolar smooth muscle, causing vasodilation; hair growth effects are secondary to vasodilation. MINOXIDIL TOPICAL (ROGAINE EXTRA STRENGTH) Stimulates hair growth in general and is effective in many types of hair loss. Exact mechanism of action remains unclear, but does not appear to have either hormonal or immunosuppressant effects. The 5% solution appears to be more effective. DOSING ADULT 33 Falling Hair Problems & Probable cure… 6 January 2011 Apply <25 gtt bid regardless of extent of affected area. PEDIATRIC Not established INTERACTIONS Concurrent use with guanethidine, diuretics, or hypotensive agents may result in additive hypotension CONTRAINDICATIONS Documented hypersensitivity, pheochromocytoma, coronary artery disease, cardiac dysrhythmias, congestive heart failure, or valvular heart disease, pregnancy, breastfeeding PRECAUTIONS PREGNANCY C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus PRECAUTIONS May exacerbate angina pectoris; caution in pulmonary hypertension, congestive heart failure, coronary artery disease, and significant renal failure FOLLOW-UP DETERRENCE/PREVENTION Alopecia areata is highly unpredictable. No treatment is effective in preventing or halting progression of the condition. No trigger can be found to explain disease exacerbation in most patients. PROGNOSIS The natural history of alopecia areata is unpredictable. Most patients have only a few focal areas of alopecia, and spontaneous regrowth usually occurs within 1 year. Estimates indicate less than 10% of patients experience extensive alopecia and less than 1% have alopecia universalis. Patients with extensive long-standing conditions are less likely to experience significant longlasting regrowth. Adverse prognostic factors include nail abnormalities, atopy, onset at a young age, and severe forms of alopecia areata. 34 Falling Hair Problems & Probable cure… 6 January 2011 PATIENT EDUCATION Patient education is a key factor in alopecia areata. Inform patients of the chronic relapsing nature of alopecia areata. Reassure patients that the condition is benign and does not threaten their general health. Most patients try to find an explanation about why this is happening to them. Reassure these patients that they have done nothing wrong and that it is not their fault. Inform patients that expectations regarding therapy should be realistic. Support groups are available in many cities; it is strongly recommended that patients be urged to contact the National Alopecia Areata Foundation at 710 C St, Suite 11, San Rafael, CA 94901 or view the Web site. Many patients are reluctant to use hairpieces or take part in support groups because, at first, these often are perceived as last-resort options. Take the time to discuss the options with patients because they are of great benefit. MISCELLANEOUS MEDICOLEGAL PITFALLS Failure to discuss at length realistic treatment expectations and treatments that have serious adverse effects or are not approved by the Food and Drug Administration (ie, topical immunotherapy) Medscape Medical Malpractice and Legal Issues Resource Center MULTIMEDIA 35 Falling Hair Problems & Probable cure… 6 January 2011 MEDIA FILE 1: ALOPECIA AREATA AFFECTING THE BEARD. MEDIA FILE 2: ALOPECIA AREATA AFFECTING THE ARMS. 36 Falling Hair Problems & Probable cure… 6 January 2011 MEDIA FILE 3: PATCHY ALOPECIA AREATA. 37 Falling Hair Problems & Probable cure… 6 January 2011 MEDIA FILE 4: OPHIASIS PATTERN OF ALOPECIA AREATA. MEDIA FILE 5: SISAIPHO PATTERN OF ALOPECIA AREATA. 38 Falling Hair Problems & Probable cure… 6 January 2011 MEDIA FILE 6: ALOPECIA TOTALIS. MEDIA FILE 7: DIFFUSE ALOPECIA AREATA. 39 Falling Hair Problems & Probable cure… 6 January 2011 MEDIA FILE 8: CORTICOSTEROID INJECTION. 40 Falling Hair Problems & Probable cure… 6 January 2011 MEDIA FILE 9: TREATMENT ALGORITHM FOR ALOPECIA AREATA. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. van der Steen P, Traupe H, Happle R, Boezeman J, Sträter R, Hamm H. The genetic risk for alopecia areata in first degree relatives of severely affected patients. An estimate. Acta Derm Venereol. Sep 1992;72(5):373-5. [Medline]. Colombe BW, Lou CD, Price VH. The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis. J Investig Dermatol Symp Proc. Dec 1999;4(3):216-9. [Medline]. Colombe BW, Price VH, Khoury EL, Garovoy MR, Lou CD. HLA class II antigen associations help to define two types of alopecia areata. J Am Acad Dermatol. Nov 1995;33(5 Pt 1):757-64. [Medline]. Price VH, Colombe BW. Heritable factors distinguish two types of alopecia areata. Dermatol Clin. Oct 1996;14(4):679-89. [Medline]. Jackow C, Puffer N, Hordinsky M, Nelson J, Tarrand J, Duvic M. Alopecia areata and cytomegalovirus infection in twins: genes versus environment?. J Am Acad Dermatol. Mar 1998;38(3):418-25. [Medline]. Safavi K. Prevalence of alopecia areata in the First National Health and Nutrition Examination Survey. Arch Dermatol. May 1992;128(5):702. [Medline]. Safavi KH, Muller SA, Suman VJ, Moshell AN, Melton LJ 3rd. Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989. Mayo Clin Proc. Jul 1995;70(7):62833. [Medline]. Muller SA, Winkelmann RK. Alopecia areata. An evaluation of 736 patients. Arch Dermatol. Sep 1963;88:290-7. [Medline]. Sharma VK, Dawn G, Kumar B. Profile of alopecia areata in Northern India. Int J Dermatol. Jan 1996;35(1):22-7. [Medline]. Puavilai S, Puavilai G, Charuwichitratana S, Sakuntabhai A, Sriprachya-Anunt S. Prevalence of thyroid diseases in patients with alopecia areata. Int J Dermatol. Sep 1994;33(9):6323. [Medline]. Werth VP, White WL, Sanchez MR, Franks AG. Incidence of alopecia areata in lupus erythematosus. Arch Dermatol. Mar 1992;128(3):368-71. [Medline]. Wang SJ, Shohat T, Vadheim C, Shellow W, Edwards J, Rotter JI. Increased risk for type I (insulin-dependent) diabetes in relatives of patients with alopecia areata (AA). Am J Med Genet. Jul 1 1994;51(3):234-9. [Medline]. Perini GI, Veller Fornasa C, Cipriani R, Bettin A, Zecchino F, Peserico A. Life events and alopecia areata. Psychother Psychosom. 1984;41(1):48-52. [Medline]. Tosti A, De Padova MP, Minghetti G, Veronesi S. Therapies versus placebo in the treatment of patchy alopecia areata. J Am Acad Dermatol. Aug 1986;15(2 Pt 1):209-10. [Medline]. Vestey JP, Savin JA. Natural history of severe alopecia areata. Br J Dermatol. Oct 1987;117(4):531. [Medline]. Chang KH, Rojhirunsakool S, Goldberg LJ. Treatment of severe alopecia areata with intralesional steroid injections. J Drugs Dermatol. Oct 2009;8(10):909-12. [Medline]. Tosti A, Piraccini BM, Pazzaglia M, Vincenzi C. Clobetasol propionate 0.05% under occlusion in the treatment of alopecia totalis/universalis. J Am Acad Dermatol. Jul 2003;49(1):96-8. [Medline]. Hoffmann R, Happle R. Topical immunotherapy in alopecia areata. What, how, and why?. Dermatol Clin. Oct 1996;14(4):739-44. [Medline]. Rokhsar CK, Shupack JL, Vafai JJ, Washenik K. Efficacy of topical sensitizers in the treatment of alopecia areata. J Am Acad Dermatol. Nov 1998;39(5 Pt 1):751-61. [Medline]. Wiseman MC, Shapiro J, MacDonald N, Lui H. Predictive model for immunotherapy of alopecia areata with diphencyprone. Arch Dermatol. Aug 2001;137(8):1063-8. [Medline]. El-Zawahry BM, Bassiouny DA, Khella A, Zaki NS. Five-year experience in the treatment of alopecia areata with DPC. J Eur Acad Dermatol Venereol. Mar 2010;24(3):264-9. [Medline]. Tang L, Cao L, Sundberg JP, Lui H, Shapiro J. Restoration of hair growth in mice with an alopecia areata-like disease using topical anthralin. Exp Dermatol. Jan 2004;13(1):510. [Medline]. 41 Falling Hair Problems & Probable cure… 6 January 2011 23. Taylor CR, Hawk JL. PUVA treatment of alopecia areata partialis, totalis and universalis: audit of 10 years' experience at St John's Institute of Dermatology. Br J Dermatol. Dec 1995;133(6):914-8. [Medline]. 24. Sharma VK. Pulsed administration of corticosteroids in the treatment of alopecia areata. Int J Dermatol. Feb 1996;35(2):133-6. [Medline]. 25. Price VH, Willey A, Chen BK. Topical tacrolimus in alopecia areata. J Am Acad Dermatol. Jan 2005;52(1):138-9. [Medline]. 26. Joly P. The use of methotrexate alone or in combination with low doses of oral corticosteroids in the treatment of alopecia totalis or universalis. J Am Acad Dermatol. Oct 2006;55(4):6326. [Medline]. 27. Ross EK, Bolduc C, Lui H, Shapiro J. Lack of efficacy of topical latanoprost in the treatment of eyebrow alopecia areata. J Am Acad Dermatol. Dec 2005;53(6):1095-6. [Medline]. 28. Price VH. Treatment of hair loss. N Engl J Med. Sep 23 1999;341(13):964-73. [Medline]. 29. Strober BE, Siu K, Alexis AF, Kim G, Washenik K, Sinha A, et al. Etanercept does not effectively treat moderate to severe alopecia areata: an open-label study. J Am Acad Dermatol. Jun 2005;52(6):1082-4. [Medline]. 30. van den Biggelaar FJ, Smolders J, Jansen JF. Complementary and alternative medicine in alopecia areata. Am J Clin Dermatol. 2010;11(1):11-20. [Medline]. 31. Willemsen R, Haentjens P, Roseeuw D, Vanderlinden J. Hypnosis in refractory alopecia areata significantly improves depression, anxiety, and life quality but not hair regrowth. J Am Acad Dermatol. Mar 2010;62(3):517-8. [Medline]. 32. McElwee KJ, Tobin DJ, Bystryn JC, King LE Jr, Sundberg JP. Alopecia areata: an autoimmune disease?. Exp Dermatol. Oct 1999;8(5):371-9. [Medline]. KEYWORDS alopecia areata, hair loss, autoimmune alopecia, baldness CONTRIBUTOR INFORMATION AND DISCLOSURES AUTHOR Chantal Bolduc, MD, FRCP(C), Assistant Professor, Department of Dermatology, University of Montreal Chantal Bolduc, MD, FRCP(C) is a member of the following medical societies: Canadian Dermatology Foundation Disclosure: Nothing to disclose. COAUTHOR(S) Harvey Lui, MD, FRCPC, Professor and Head, Department of Dermatology and Skin Science, Vancouver General Hospital, University of British Columbia; Medical Director, The Skin Centre, Lions Laser Skin Centre and Psoriasis and Phototherapy Clinic, Vancouver General Hospital Harvey Lui, MD, FRCPC is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Society for Laser Medicine and Surgery, American Society for Photobiology, Canadian Dermatology Association, Canadian Dermatology Foundation, Canadian Medical Association, College of Physicians and Surgeons of British Columbia, European Academy of Dermatology and Venereology, National Psoriasis Foundation, North American Hair Research Society, and Photomedicine Society Disclosure: Astellas Consulting fee Review panel membership; Amgen/Wyeth Consulting fee Speaking and teaching; LEO Pharma Honoraria Speaking and teaching; LEO 42 Falling Hair Problems & Probable cure… 6 January 2011 Pharma Grant/research funds Investigator; Serono Grant/research funds Investigator; Galderma Grant/research funds Other Jerry Shapiro, MD, FRCP(C), Clinical Associate Professor, Department of Medicine, Division of Dermatology, University of British Columbia, Canada Disclosure: Nothing to disclose. MEDICAL EDITOR Leonard Sperling, MD, Chair, Professor, Department of Dermatology, Uniformed Services University of the Health Sciences Leonard Sperling, MD is a member of the following medical societies: American Academy of Dermatology Disclosure: Nothing to disclose. PHARMACY EDITOR Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association Disclosure: Nothing to disclose. MANAGING EDITOR Lester F Libow, MD, Dermatopathologist, South Texas Dermatopathology Laboratory Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Texas Medical Association Disclosure: Nothing to disclose. CME EDITOR Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator CHIEF EDITOR Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center Dirk M Elston, MD is a member of the following medical societies: American Academy of 43 Falling Hair Problems & Probable cure… 6 January 2011 Dermatology Disclosure: Nothing to disclose. 44 Falling Hair Problems & Probable cure… 6 January 2011
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Systems Administrator II
Sheridan Memorial Hospital is a progressive, state-of-the-art facility nestled beneath the Big Horn Mountains in beautiful Northeast Wyoming. Founded over 100 years ago, Sheridan Memorial is licensed for 88 beds with over 60 physicians who provide primary medical care and specialty care in more than 15 areas. We are proud of our more than 600 employees who provide personalized, patient centered care in a healing environment. When people think of excellent healthcare, they think of Sheridan.JOB SUMMARYSystems administrator maintains and ensures security, availability, and performance of computers, servers and networks in a multi-site Windows environment. Needs to be passionate about technology and know how to best meet end user and business needs. System Administrator is responsible for the technical design, planning, implementation, performance tuning, and recovery procedures for mission critical enterprise systems. Serves as a technical expert in the area of system administration for Windows operating systems as well as a specialization in at least two of the following: VMware, Citrix XenApp/XenDesktop, Microsoft Exchange, Cloud services, etc. This position also recommends the redesign and configuration of operating systems and system applications. Performs a broad range of responsible and complex computer systems administration duties in the implementation and maintenance of management information systems; to provide technical support for a combination of desktop, server and network hardware, software and peripheral equipment; to upgrade existing hardware and software, to correct reported hardware and/or software problems; and to perform a variety of technical tasks relative to assigned area of responsibility.
- Provide engineering solutions for various project and operational needs.
- Install new/rebuild existing servers and configure hardware, peripherals, services, settings, directories, storage, etc. in accordance with standards and project/operational requirements.
- Develop and maintain installation and configuration procedures.
- Contribute to and maintain system standards.
- Research and recommend innovative, and where possible automated approaches for system administration tasks; identify approaches that leverage our resources and provide economies of scale.
- Perform daily system monitoring, verifying the integrity and availability of all hardware, server resources, systems and key processes, reviewing system and application logs.
- Provide Tier II/III other support per request from various sources; investigate and troubleshoot issues.
- Repair and recover from hardware or software failures; coordinate and communicate with impacted departments.
- Apply patches, packages and upgrades on a regular basis, to the latest code releases.
- Perform periodic performance reporting to support capacity planning.
- Perform ongoing performance tuning, hardware upgrades, and resource optimization as required.
- Maintain data center environmental and monitoring equipment.
- Accountable for outstanding customer service to staff and team members.
- Develops and maintains effective relationships through effective, timely communication and meets deadlines.
- Takes initiative and action to respond, resolve and follow up regarding customer service issues with all customers in a timely manner.
- Maintains and ensures security, availability and performance of computers, servers and networks in a multi-site Windows Server LAN/WAN/WLAN environment.
- Effectively troubleshoots problems reported by users and follows up to ensure problems are resolved satisfactorily.
- Clearly documents all IT procedures and follows best practice change management for configuration changes to IT systems
- Manages and monitors backup systems. Regularly tests and verifies restore capabilities.
- Assists with disaster recovery planning and the recovery of vital information.
- Administers cloud-based services such as Cerner, Infor, etc.
- Creates CCL, scripting such as a batch, VBscript, and Powershell scripts to perform automated tasks.
- Ensures availability of network services (DNS, DHCP, Active Directory, NPS).
- Interacts with laptops and workstations in a client-server environment. Ensures devices interconnect seamlessly with diverse systems including authentication servers, file servers, email servers, application servers and administrative systems.
- Maintains anti-virus/anti-malware protection and security control.
- Works with vendor support contacts as needed to resolve technical issues.
- Builds, configures, and maintains servers and other assets.
- Researches solutions to enhance or replace existing hardware and software.
- Performs other tasks and work with other departments as directed by supervisor.
MINIMUM QUALIFICATIONSEducation / Experience / License and Certifications
- Bachelor's Degree in computer science or equivalent experience.
- Minimum three years' progressive experience in various Information Technology related functions including but not limited to information server standard administration.
- Minimum three years' increasingly responsible computer applications programming and systems analysis experience.
Additional Skills
- Demonstrated competency in project management.
- Cerner experience desired.
- Demonstrated working knowledge of current communications devices and protocols, server and desktop technologies.
- Ability to manage multiple activities and tasks simultaneously.
- Facilitation and change management skills.
- Highly developed verbal and written communications.
- Ability to communicate in English; both verbally and in writing
- Excellent customer service skills
- Knowledge of Word, Excel, PowerPoint and Access expected
- Efficient use of MHSC help desk application is required
Sheridan Memorial Hospital is an equal opportunity/Affirmative Action employer and gives consideration for employment to qualified applicants without regard to age, race, color, religion, sex, national origin, disability or protected veteran status. If you'd like more information about your EEO rights as an applicant under the law, please click here.
Specific demands not listed: Possible exposure to blood and or body fluids / infectious disease / hazardous waste requiring the use of Personal Protective Equipment. Exposure to odorous chemicals / specimens and Latex products.
Pre-employment drug and alcohol screening is required.

subset: commoncrawl


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Numbers Zombie is an exciting new game that lets kids have fun while learning the numbers. You take the role as a cute zombie running around the beach picking up numbers in correct order.
There are lots of different levels that teach you different types of numbers. The first levels teaches you the basic numbers from 1 to 10, while later levels will teach your prime and square numbers.
The game is easy to learn and lots of fun to play, it will keep kids busy for hours!
- 24 different levels.
- 6 categories of numbers to learn
- Teaches difference between odd and even numbers
- Teaches difference between positive and negative numbers
- Teaches prime and square numbers.
- Fun graphics and animated zombie character
- Entertaining sound effects and music
- Game Center and highscores
The game is designed for kids 4 to 8 learning numbers for the first time. It is completely free from ads and in-app-purchases.


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FPSC goes online for recruitments
Islamabad, March 02: Federal Public Service Commission (FPSC) has launched online application system for all general recruitments which will be operational from April 2013 and this fast tracking system will benefit more one hundred thousand students apply for around 1000 seats annually. The online system will also be adopted for the Central Superior Services (CSS) from the next year.
Previously, FPSC usually took 10 to 12 months to complete the lengthy process and now after installation of this new online system such a lengthy process could be completed in simply three-month time.
A press release issued by the system says that all applications for general recruitment in BS-16 and above shall only be invited online through consolidated advertisement No.04/2013 (April, 2013) to be published in newspapers on the first Sunday of April, 2013 i.e. 7.4.2013. Applications on manual forms and hard copies of certificates, degrees etc. will no longer be a requirement.
FPSC press release reads, "Screening tests for general recruitment will now be conducted on bi-monthly basis. To facilitate the candidates, admission certificates for general recruitment cases shall be placed online on website of FPSC www.fpsc.gov.pk after the provisional acceptance of their candidature and candidates will be intimated about their written test through FPSC website and SMS. Candidates are therefore, advised to visit FPSC website frequently after having filed their online applications. FPSC has further decided that after acceptance of their candidatures:
(i) It will be mandatory for the candidates to bring original CNIC and down loaded admission certificates as well as original treasury receipts at the time of reporting for written test.
(ii) To determine eligibility of the candidates for posts requiring experience, the pre-selected candidates in the ratio of 1:5 for merit vacancies and 1:3 for provincial and regional quota's vacancies will be required to furnish requisite documents within 15 days of the receipt of intimation from the Commission.
(iii) Candidates called for interview will bring their original documents as well as one set of attested documents for scrutiny and record at the time of the interview.
(iv) "Candidates, whose documents are found deficient will be provisionally interviewed but will be required to provide proof of their eligibility within a period of 7 days without fail otherwise their candidature will be cancelled."
It further adds, "The online application system will offer convenience to the applicants in general recruitment cases. They will no longer be required to collect manual application forms and deposit those in the FPSC Offices. They will also not be required to furnish copies of documents at the time of online applications, which may be done on 24/7 basis rather than just within specific office timings. Online applications will have the facility of receiving instant confirmation and will be able to receive SMS intimations also. It may be pointed out that FPSC receives more than one hundred thousand (100000) applications each year for over 1000 vacancies. The launching of online application system will streamline the process, provide significant advantage and facility to the applicants and will significantly reduce processing time of cases as well". The news
6,000 laptops given to PhD, M.Phil scholars
Lahore: Chief Minister Shahbaz Sharif has said the provision of resources for the improvement of education sector is not expenditure but a useful investment and right of the youth which the Punjab government has fulfilled efficiently.
The chief minister was speaking at a laptops distribution ceremony among PhD and M.Phil scholars from all over Punjab at the Oval Ground of Government College University on Friday. Laptops were given to 6,000 PhD and M.Phil scholars on merit.
Mr Shahbaz said that scholars should use the laptops to develop new methods of generating energy through alternative sources, utilization of natural resources, elimination of energy crisis and increase in agriculture production.
He said the Punjab government took revolutionary steps for the welfare of male and female students and uplift of the education sector during the last five years.
He said that laptops worth Rs8 billion were distributed among university students and the Ujala Programme had been launched with an amount of Rs2.5 billion to provide solar panels to talented students of government schools on merit.
The chief minister said since Pakistan was far behind in the field of science and technology there was a need for development in information technology, science and research for putting the country and the nation on the road to prosperity.
He said the process of distribution of laptops, started for creating awareness among youth about information technology, would bring positive results as students would have an access to modern knowledge and bring the country on a par with the developed nations.
He said laptops could be helpful in the preparation of recommendations for improvement of economy.
Mr Shahbaz said that there was a lack of positive contacts between the faculty and industry, trade and agriculture and called for improving these contacts. Stating that if leadership was committed, the destiny became easier, Mr Shahbaz said the resolution of country's problems was difficult but not impossible.
He said the Punjab government created the Punjab Education Endowment Fund having Rs10 billion reserves and added that over 40,000 male and female students were getting education in local and foreign educational institutions through this fund.
The chief minister said that Daanish schools, established in backward areas, were better than Aitchison and Grammar schools. He said medical colleges and women universities had also been set up.
The chief minister presented laptops to PhD and M.Phil scholars. GCU Vice-Chancellor Prof Dr Kahleequr Rahman and Punjab Higher Education secretary Dr Ijaz Munir also spoke. Dawn


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FINDLAY, Ohio — American Tire Distributors (ATD) Inc.'s Hercules Tires business has extended its sponsorship portfolio by aligning professional anglers Josh Bertrand and Josh Douglas with Team Hercules for the 2019 fishing season.
Bertrand won the 2018 Bassmaster Elite at the St. Lawrence River and has 14 professional-level top 10 finishes, as well as four Bassmaster Classic qualifications and a Bassmaster Elite series win.
He will be one of the 80 anglers participating in the 2019 New Bass Pro Tour.
Bertrand said he's excited to be part of the Hercules family. "I log a lot of miles on the road between competitions every year and having Hercules be a part of what gets me where I need to go is very reassuring."
Mr. Douglas gained notoriety with the Minnesota state B.A.S.S. Federation before expanding his reach into the national circuit. A competitor on the FLW Tour and the Bassmaster Eastern Open, he has several top 10 finishes, including a third place in the 2018 FLW Tour event in Gilbertsville, KY.
Mr. Douglas owns and operates a guide service on Lake Mille Lacs, Minn., helping anglers of all skill levels find and catch smallmouth bass.
"As a professional fisherman and guide who takes clients into remote areas, I have to be able to count on my equipment, and I know I can count on Hercules Tires," Mr. Douglas said. "Hercules Tires have always performed well for me and I'm thrilled to be a part of Team Hercules."
As part of the agreement, Messrs. Bertrand and Douglas will feature the Hercules Tires' logo on their boat and outerwear and will run their trucks on Terra Trac AT II tires, which Herclues said can handle the harshest elements in every condition on every surface.
In addition, Mr. Bertrand has Hercules Power ST2 tires on his boat trailer. The specialty trailer tire is designed to reduce rolling resistance and improve fuel economy while promoting long-lasting wear, according to Hercules
Nakia Medlin, Hercules Tires director of marketing, said both fishermen fit perfectly with the brand. "We want to show that Hercules is a quality tire option for everyone who loves outdoor activities and we're very excited to share that message with fans of professional fishing everywhere."


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Orlando Visitors Guide
Our Orlando Visitors Guide provides a brief oversight to where to go, where to stay and what to do.
In 2015 Orlando welcomed over 66 million visitors, which is more visitors than most countries receive each year. The primary areas of interest for most out of state and international purchasers are Davenport and Kissimmee, where short term rentals are permitted and in Dr Phillips which is popular with families looking for luxury second homes.
Places to stay and explore in our Orlando Visitors Guide
Davenport is in itself a relatively a small town located southwest of Orlando. Davenport has become known as an area where vacation homes are in high demand. With its central location, surrounded by rolling hills the land that was once used for citrus growth. Davenport's central location makes it a perfect spot to base your Florida vacation. Disney World is less than thirty minutes away from Davenport. It is also just minutes to Epcot, Universal Studios, Seaworld of Orlando, Wet and Wild, Gatorland, and much more.
Kissimmee, Orlando, Florida – When many visitors think of Orlando and Disney, they automatically think of Kissimmee. It has been paraded around, advertised and sold as THE place to stay when visiting Orlando for what seems like decades.
Kissimmee offers a little something for everyone and boasts properties, real estate and vacation homes in most price ranges and categories. Gated communities, resort communities, vacation homes and exclusive estate homes, lakefront homes and golf course homes, apartments and condos you will find it here in Kissimmee.
Kissimmee is the county seat and where most of the county's activity occurs. The backdrop of the city is dominated by tourist attractions and overnight accommodations. Most notably, the Walt Disney World Resort lies at Kissimmee's doorstep, and roughly 150 hotels and motels are located in and around Kissimmee.
Dr Phillips
Dr Phillips and its communities have garnered a prestigious name for themselves over the years. Not just because of the address or the stunning homes located here but also because of the quality public schools which boast strong reputations within these zip codes.
Located close to Downtown Orlando, the International Airport as well as the theme parks, the Dr Phillips area has evolved into an area of Orlando where upscale condos, spacious family estates and opulent single family homes are in demand by residents, second home buyers and wealthy vacation home buyers who appreciate the finer things in life.
Orlando Theme Parks
|Animal Kingdom
|Harry Potter
Orlando Recreation & Days Out
|Visit OrlandoParks and Recreation
| Amway Center
Daytona International Speedway
Beaches Near Orlando
|West Coast
|East Coast
Orlando Shopping
|Mall at Millenia
Orlando Premium Outlets I-Drive
Orlando Premium Outlets Lake Buena Vista
|Walmart Supercenter


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WELCOME! It is a privilege to get in touch with you. Dhananjaya Tours is into its third generation and that is enough for you believe in our excellent quality of service. We started back in 1970, half a century ago as a small tour organiser between India and Sri Lanka. Back then Dhananjaya Tours was one of the four tour organisers in the country. And today we are one of the leading foreign tour companies in Sri Lanka. Hats off for our customers and other stakeholders, because you are the secret of our success.
I and my family thoroughly enjoyed the tour. From the airport pick up to the drop off, everything was simply fantastic. I am looking forward tour Singapore next time with Dhananjaya Tours. Sunil Hewawasam
We wanted to customize our tour. Dhananjaya Tours helped us to organise the tour to suit to our requirements. The tour was well organised. We thoroughly enjoyed. I highly recommend. Kamal Perera
It was dream come true. From my childhood I had a dream to send my parents to India for a pilgrimage tour. I was looking for a reliable and trustworthy tour organiser. I am glad that I chose Dhananjaya Tours. My parents are happy and so am I. Excellent customer service and reasonable prices. Thank you Dhananjaya Tours! Supun Amarasekara


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The Virtual Classes at Home program is now available for registrations! It is a fully interactive web based program that allows kids to stay active, have fun and practice basic skills at home. To learn more and register...
Like us on Facebook!!! For program updates, class announcements, pictures from our sessions and useful tips and information on how to help develop the skills of your soccer player please do not forget to visit and like u...
Looking for fun, enthusiastic soccer skills class for your little one? Soccer Sparks offers age-appropriate soccer skills curriculums for kids ages 2-12 in the Dallas Fort Worth Metroplex, Texas and Vermont!
Soccer Sparks
Plano, Texas
Phone: 469-878-8550
Email: [email protected]


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A Ram and Jeep dealer in Post Falls, Idaho, was offering free elk taxidermy with the purchase of a new truck. Sadly, the promotion ended yesterday.
Now, is this type of promotion commonplace? I honestly have no idea, but it sure seems novel. Offering free taxidermy of any sort with the purchase of a new car or truck is certainly one thing, but the specificity of the elk really drives it home.
"Hi, I'm looking to buy your blue Ram 1500 Laramie and I just took down this pronghorn that I'd like to get taxidermied for free."
"I'm sorry, sir, the promotion only covers elk. But about that Laramie ..."
For those wondering, it does seem to be general elk hunting season in Idaho, but after a brief look at Idaho's extensive Big Game Seasons and Rules guide, there is a dizzying number of rules and regulations regarding exactly when and where one can hunt elk as well as what kind of elk one can hunt. Try reading that sentence out loud.
Nevertheless, it would logically seem that free elk taxidermy could be enticing for those living in the area of Post Falls, which is in between Coeur d'Alene and Spokane, Washington, near the state border. So hey, why not? Way to get creative Findlay Chrysler Dodge Jeep Ram.
According to the advertisement, the dealer would only cover $1,500 worth of elk taxidermy. Is that enough for a quality taxidermification of your elk? Again, I'd rather not Google that. But it's nevertheless something, right?
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Our days are full. Full of love and life.
It's Saturday morning and all is quiet. Rob is home for the weekend so he and Will are at the golf course. Jim is at the Global Mission Focus Weekend breakfast.
I am putting off…cleaning, planning and making a list for the Thanksgiving holiday. There is room in the refrigerator for the turkey to thaw. I need to write out the script for speaking in 2 ABF's in the morning. ABF is what our church calls adult Sunday schools; Adult Bible Fellowship.
I have the slide show ready. During the last training module with Entrust, I learned the how to's of preparing a message. I already practiced most of it but the discipline of rehearsals and working against a clock was good! Continuing to improve my skills in teaching, speaking and facilitating is important to me. I have learned so much through those 4 modules Completing them in 16 months was a marathon but so worth it. Normally it takes 2 – 3 years because of cost and schedules. Having both was a huge blessing from God. The real blessing is training others! Growing with them in Christ and improving ministry skills is exciting.
JIm's long awaited ENT specialist appointment went well. The doctor prescribed a course of treatment and possible therapy. At long last. Praying it will all be effective.
Dinner last night with all of us here was a love feast for me. Having them all around hte table is something I will never tired of or take for granted. We spent too many years spread out over 3 continents. Note, not counties, cities or countries. Continents!
Rob returns with his girlfriend Wednesday after their classes are over. Graduation adn job hunting is formost on thier minds. Less than a month away!
Nancy, Nathan and Sweet Peas are off to his sister's where they will all converge. His brother in law deploys Saturday. I remember those days. Bittersweet to celebrate those last ….before deployments of husband and son.
The chairs around the table will be fewer. No matter.
Our days are full. Full of love and life.