diagnostic criteria include generalized papular and sclerodermoid eruption , mucin deposition with fibroblast proliferation , monoclonal gammopathy and the absence of thyroid disease . skin lesions are characterized by multiple firm waxy papules , often in a linear arrangement . erythema and edema , infiltrated plaques , diffuse sclerodermoid induration , acrosclerosis , leonine facies and alopecia may also occur [ 2 , 3 ] . deposition of mucin in nodular lesions is very rare and has been only sporadically reported [ 4 , 5 , 6 ] . in addition to cutaneous manifestations , extracutaneous involvement is present in the majority of patients , and is associated with severe morbidity and increased mortality [ 2 , 3 , 7 ] . a variety of different therapeutic approaches for dealing with this chronic and progressive mucin deposition disorder have been used . compared to older drugs , intravenous immunoglobulin ( ivig ) has shown excellent results with a good safety profile . a 42-year - old male had been well until december 2008 , when he noted progressive swelling of the face , hands and forearms , accompanied by pruritus , increased hair loss , arthralgia , myalgia and fatigue . in the following weeks , skin induration of the hands and forearms , papular eruption on the neck and upper trunk , and nodular lesions on the face and fingers developed . the patient was admitted to the local hospital , where systemic fibrosing disorder was suspected and systemic glucocorticoid treatment ( methylprednisolone 1 mg / kg body weight ) was introduced . since only partial regression of the facial and hand edemas was observed , he was referred to the university medical centre ljubljana , initially to the department of rheumatology and later to the department of dermatovenereology . at admission in february 2009 , dense papular lesions were present on the neck , retroauricular areas , scalp and upper trunk , partly in a linear arrangement . tender nodules of a hard consistency could be palpated bilaterally on the upper and lower eyelids , on the forehead , lateral parts of the nose , behind the ears and on the fingers ( fig . sclerodermoid induration of the skin with irregular loss of hair was present on the forearms . complete blood cell count , serum levels of inflammatory parameters , electrolytes , glucose , calcium , creatinine kinase , myoglobin , aldolase as well as tumor markers were within normal range . chest radiograph was normal , as were the results of lung function tests , abdominal ultrasound , echocardiography , nailfold capillaroscopy , radiographs of the hands and feet and bone marrow examination . since electromyography detected signs consistent with myopathy , neurological examination and muscle biopsy were performed . the former revealed no pathology but the biopsy demonstrated mild myopathy with atrophy involving selectively type 2 fibers without inflammation . biopsies of the nodules on the hand and periorbital region and of papular lesions on the trunk were performed . there was abundant proliferation of large stellate fibroblasts in the reticular dermis and subcutis , with prominent deposits of a myxoid substance between thick collagen bundles . 2 ) . according to the clinical picture and histopathology , a diagnosis of scleromyxedema was established . treatment with thalidomide was introduced ( initial dosage 100 mg / day ) and the previously prescribed glucocorticoid gradually tapered off and discontinued . after 3 months of thalidomide treatment , only a partial regression of the skin lesions was achieved . therefore , additional treatment with high - dose ivig was introduced ( 0.4 g / kg body weight / day for 5 consecutive days every month for the duration of 6 months ) . after only two cycles of ivig , a marked regression of the nodular lesions on the face and hands and improvement of the papular and sclerodermoid mucinosis was observed . thereafter , he received four additional cycles of ivig at the same dosage at 8-week intervals . treatment with thalidomide was continued with a lower daily dose ( 50 mg / day ) and finally discontinued in july 2011 due to complete disease remission ( fig . the patient reported numbness in his feet ; however , electromyographic investigation did not confirm a peripheral sensory neuropathy . monoclonal gammopathy could not be demonstrated , even though a more sensitive diagnostic method ( immunofixation electrophoresis ) was performed . according to the recent classification , cases without monoclonal gammopathy are classified under atypical forms [ 1 , 2 ] . it is not clear whether they represent a primary or a secondary phenomenon in the pathogenesis . in clinical observations , paraprotein levels did not correlate with disease severity [ 7 , 9 , 10 , 11 ] . monoclonal gammopathy has been found in 88100% of patients and has usually been of igg  light chains [ 3 , 7 , 9 , 12 ] . paraproteinemia is generally present at the beginning of disease , though a delayed appearance should also be considered [ 1 , 6 , 13 ] . other reported associations include biclonal gammopathy [ 3 , 12 , 14 ] . in our patient , due to sclerodermoid skin lesions on the face , forearms and hands , and initial extracutaneous symptoms , systemic sclerosis was first suspected . proximal muscle weakness , myositis , polyarthritis and gastrointestinal involvement with dysphagia have been reported in 6090% of patients with scleromyxedema [ 3 , 9 , 12 ] and may be prominent . cardiovascular , lung , renal , hematological and peripheral and central nervous system disorders have been also reported with different frequencies , ranging from 10 to 60% [ 3 , 7 , 9 , 12 ] . in such cases later in the course of the disease , atypical nodular lesions with abundant mucin deposits in the cutis and subcutis developed on the face and fingers , along with typical papular and sclerodermoid eruptions . a nodular form of lichen myxedematosus is a well - established entity among localized mucinoses . in scleromyxedema , nodules have been reported only sporadically , concomitantly with a papular or sclerodermoid pattern of mucinosis [ 4 , 5 , 6 , 16 ] , as in our case . interestingly , in three of these cases monoclonal paraproteinemia could not be demonstrated either [ 4 , 5 , 6 ] . manifestations of scleromyxedema in the ocular region have been found in 24% of patients , most commonly as thickened skin of the eyebrow and eyelids , palpebral edema , ectropion and lagophthalmos . to our knowledge , skin involvement of the eyelids with mucinous nodules has been reported only once before , with nodules defined as myxomas . apart from the terminology , we believe that it is important to distinguish lesions in scleromyxedema , which may vary according to the quantity and depth of myxoid tissue , from true neoplasms ( cutaneous myxomas as part of the carney complex and cutaneous angiomyxomas ) . cutaneous angiomyxomas are mostly solitary tumors with an additional vascular and sometimes an epithelial component [ 18 , 19 ] , both of which were absent in our patient . various therapeutic agents have been used : high - dose corticosteroids , a variety of immunosuppressive and chemotherapeutic drugs , puva and uva1 phototherapy , plasmapheresis , extracorporeal photopheresis , electron beam therapy , -interferon , retinoids , thalidomide , ivig , bortezomib and autologous stem cell transplantation [ 1 , 3 , 9 , 15 , 20 , 21 , 22 ] . treatment with high - dose ivig has been found to be especially promising in the last decade . good results have been documented in cases with a papular and sclerodermoid pattern of mucinosis [ 7 , 8 , 9 , 11 , 14 , 15 , 23 ] . based on previous reports [ 10 , 24 , 25 ] , we decided to treat our patient initially with thalidomide . after 3 months , we observed only a moderate improvement of the cutaneous lesions . to improve the treatment response and to avoid potential thalidomide toxicity , especially peripheral sensory neuropathy , both drugs have complex immunomodulatory actions and antifibrotic properties [ 10 , 24 , 25 ] . their combination probably allows less frequent administration of ivig and treatment with lower doses of thalidomide . in contrast to previous reports [ 7 , 9 , 23 ] , maintenance infusions of ivig for a sustained treatment response were not required in our patient . the disease duration before treatment introduction probably also has an impact on the further course of the disease . the mean duration of skin disease at diagnosis was found to range from 10 to 12 months [ 7 , 12 ] to several years . thus , the disease duration of 3 months in the present case was rather short . treatment experiences in nodular or other atypical eruptions in scleromyxedema are based on sporadic reports . an extensive nodular variant on the face regressed after radiation therapy . in a patient with orbital myxomas , a marked improvement was observed with cyclophosphamide but with serious side effects . in an unusual tumorous variant of scleromyxedema , a highly favorable result was reported with ivig . in a recent report of disseminated subcutaneous nodules , the patient was treated with low - dose isotretinoin but was lost to follow - up . in conclusion , the present case of scleromyxedema may add new insight into the clinical diversity of this mysterious disease . in an unusual presentation with nodular lesions , including also the periorbital region , successful treatment with a contemporary treatment approach is presented for the first time . combination of thalidomide and ivig may be suggested as a good treatment option also in more severe forms of cutaneous mucin deposits in scleromyxedema .
scleromyxedema is a rare cutaneous mucinosis , usually presenting with generalized papular eruption and sclerodermoid induration , monoclonal gammopathy and systemic manifestations . 
 an atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely . in recent years 
 , intravenous immunoglobulin ( ivig ) appears to be the therapy of choice for scleromyxedema . 
 treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports . 
 we report the case of male patient with atypical scleromyxedema without underlying paraproteinemia , presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids , and associated systemic symptoms . 
 complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and ivig .