cryptococcus neoformans is encapsulated yeast , which can be commonly found in bird feces , plants , dust , soil and contaminated food . it is an important pathogen that causes opportunistic infections in immunocompromized individuals [ kidney transplant recipients , hiv - positive patients , patients with systemic lupus erythematosus ( sle ) , and patients on prolonged corticosteroid therapy and immunosuppressants ] . skin involvement , which occurs in 10 - 20% of patients , presents different clinical morphologies including ulcers , acneiform papules , subcutaneous nodules , and , rarely , cellulitis . cryptococcal cellulitis is indistinguishable from bacterial forms , and its delayed diagnosis has a worse outcome . our patient is a 17-year - old caucasian female student from pelotas , rio grande do sul , brazil , who was diagnosed with sle 2 years before admission . in january 2014 , sle evolved to grade iv lupus nephritis and thrombotic microangiopathy ; therefore , she was required intermittent hemodialysis and was receiving prednisone ( 40 mg / day ) , hydroxychloroquine ( 6 mg / kg / day ) and mycophenolate mofetil ( 2 g / day ) . she was admitted to santa casa de misericrdia hospital ( brazil ) , in june 2014 , after the appearance of nodular lesions in the right upper extremity and right lower extremity ( rle ) . these lesions were well - demarcated , erythematous , painful on palpation , non - pruritic , and featured local edema . initial laboratory findings revealed : hemoglobin 8.6 g / dl , white blood cell ( wbc ) count of 7710/mm , platelet count 89.000 cells / mm , serum aspartate transaminase ( ast ) 10 u / l , serum alanine transaminase ( alt ) 16 u / l , c - reactive protein ( crp ) 18.35 mg / l and erythrocyte sedimentation rate ( esr ) 58 mm . on the fourth day after admission , fever appeared , and the lesions on the rle worsened ; therefore , we opted for empirical treatment with amikacin and cefepime , and decreased the dose of prednisone to 30 mg / day . due to the lack of improvements of the skin lesions , we added vancomycin one week later , upon suspicion of bacterial cellulitis . results of blood culture ( the samples were collected on the day of admission ) initially indicated candida sp . upon direct examination . we assumed that the focus of candidemia was inside the intravenous catheter in her right internal jugular vein . therefore , intravenous ( iv ) fluconazole ( 200 mg / day ) was initiated and the catheter removed . a nodular lesion on her rle was biopsied on the fourth day of hospitalization ; pathology of the fibro - fatty tissue fragment was positive for fungi by grocott s method , and hematoxylin and eosin staining showed collections of spores without a strong inflammatory reaction or evidence of hyphae ( figure 1 ) . direct mycological examination of the biopsy showed various yeasts with a gelatinous capsule , and the culture in sabouraud s medium and mycosel agar indicated the presence of c. neoformans in intensive growth . direct examination of the blood culture obtained upon admission was repeated , and it was also positive for c. neoformans . based on these results , treatment for disseminated cryptococcosis was initiated ; prednisone was further decreased to 20 mg / day and fluconazole was discontinued . the patient was treated with amphotericin b ( 0.7 mg / kg / day , iv ) with an infusion time of 6 hours , since the patient had repeated reactions ( fever , chills and nausea ) with a shorter infusion time . flucytosine , which could also be indicated in this case , was not used due to its unavailability in our hospital and the difficulty to find it in brazil . she had no respiratory symptoms , and chest x - rays upon admission were normal . we performed a cranial computed tomography with contrast , which showed findings within normal limits . lumbar puncture revealed a clear , colorless and slightly cloudy cerebrospinal fluid ( csf ) , with a protein level of 16 mg / dl , glucose levels of 51 mg / dl and wbc count of 4 cells per mm. it was not possible to perform the cytological analysis , due to the low number of wbc . however , direct microbiological examination of the csf with clarification and indian ink staining showed the presence of c. neoformans . two weeks after the first lumbar puncture , the procedure was repeated : the csf was clear and colorless , with protein levels of 28 mg / dl , glucose levels of 38 mg / dl and wbc count of 8 cells per mm. mycological examination of csf did not reveal any growth of microorganisms . during antifungal treatment , ten days later , the patient s condition improved , and she left the isolation unit with neutrophils levels of 4011/mm , elevation of crp levels with a maximum peak of 141.44 mg / l , esr of 75 mm and no other significant laboratory abnormalities . soon after leaving this unit , the patient had fever for seven consecutive days ; her rle lesions simultaneously worsened , and the nodes spread to the chest and abdomen . bacterial cellulitis was suspected due to the worsening of the lesions , which were blistered , painful upon palpation , and showed signs of inflammation ( figure 2a ) . four days later , purulent secretion began to drain from these lesions ( figure 2b ) . this material was collected and analyzed : there was no bacterial growth , and c. neoformans was identified by direct examination . c. neoformans grew in culture . therefore , fluconazole ( 400 mg / day , iv ) was added to amphotericin b therapy . during the last week of hospitalization , her rle lesions improved ( i.e. pus draining and swelling disappeared ) ; also the pain ceased . clinically , laboratory tests previous to hospital discharge revealed hemoglobin levels of 9.2 g / dl , a wbc count of 16.700 cells per mm , platelet count of 303.000 cells per mm , ast 10 u / l and alt 4 u / l , and crp levels of 6.88 mg / l and esr of 53 mm . the patient was discharged after 42 days of iv treatment with amphotericin b. she was instructed to continue fluconazole ( 400 mg / day ) at home for 8 weeks and then reduced its dose to 200 mg / day for 1 year . cryptococcosis , which is common in severely immunocompromized hosts , has a low incidence in hiv - negative patients , approximately 1:100.000 . in the reported case , however , the risk factors were due to the underlying disease ( sle ) , which was treated by prolonged corticosteroid therapy and immunosuppressants . c. neoformans generally causes three types of infections : pulmonary cryptococcosis , cryptococcal meningitis and cutaneous cryptococcosis . the dissemination of this disease occurs when at least two noncontiguous sites are affected , which is unusual and mostly observed in hiv - positive patients . in our case , only pulmonary involvement was nt present . some studies support the importance of lumbar puncture in patients with cryptococcosis , even when cns symptoms are not observed , because asymptomatic meningitis represents a possible early diagnosis for the disease . skin involvement is rare , but it is nearly all the time a sign of disseminated disease ; it may precede the systemic symptoms even eight months before . it is important to stress the rarity and polymorphism of the skin condition , with the possible development of vesicles or blisters and the potential progression to ulceration . the initial presentation of the lesion in our patient was the presence of subcutaneous nodules , which became extensive and spread widely throughout the body over time . these lesions later became blisters that drained pus , from which we identified the intense parasitism of the fungus . cryptococcal cellulitis is a specific variety of skin involvement , and our patient had exhibited it in more than one occasion . similarly to our case , which we initially suspected to be bacterial , further reports have shown that , generally , cellulitis is initially treated with antibiotics until their failure shows the presence of a fungal infection . although rare , reported cases of cryptococcal cellulitis seem to be restricted mainly to the lower body , particularly to the lower extremities , as observed in this case report . cryptococcal cellulitis , in this kind of infections , is uncommon and undistinguishable from acute bacterial cellulitis for appearance and presentation . more than 80% of the patients with cryptococcal cellulitis are expected to survive in immunocompetent status when they receive the appropriate anti - fungal therapy . according to the current guidelines of the american society of infectious diseases , for disseminated cryptococcosis , amphotericin b combined with flucytosine it is expensive and not widely available in brazil , and was therefore not considered for treatment in this case . pappas et al . described the high variability in the therapeutic management of cryptococcosis , depending on the anatomical location and severity of the disease . the prolonged course ( 6 - 10 weeks ) of iv amphotericin b monotherapy , together with the reduction of chemotherapy to improve immune status , is a target that is set forth during the treatment of cryptococcosis . recent evidence also supports the requirement for maintenance therapy with fluconazole administered as an indefinite secondary prophylaxis , since the rate of recurrence exceeds 50% after apparently successful treatment . the mortality rate of cryptococcal cellulitis is high , and in case of renal involvement nearly all deaths occur within 2 weeks from diagnosis with or without treatment , indicating an aggressive and fulminant course of the disease . our patient had a second lumbar puncture that did not show the presence of c. neoformans ; this was the test that determined the success of the fungal induction therapy . another relevant aspect in this case was the rapid worsening of the patient s clinical status and skin lesions after leaving the isolation unit , when the number of neutrophils reached more than four times the previous count in a short period of time . for this reason , we considered the immune reconstitution inflammatory syndrome ( iris ) , which manifests as an exuberant tissue inflammation in patients undergoing rapid improvement of cellular immunity . in our case , together with autoimmune restoration there was also a concomitant decrease in immunosuppressive therapy , a condition that is predisposing to iris . this condition is also probably more common than believed by clinicians , and severe manifestations can be lethal if it is not considered .
we report here the case of a 17-year - old girl from pelotas , brazil , with systemic lupus erythematosus and disseminated cryptococcal infection . prior to diagnosis , she was a chronic user of corticosteroids and other immunosuppressive drugs . 
 her first symptoms were skin lesions that simulated bacterial cellulitis . upon suspicion 
 , we performed a biopsy and fungal infection was confirmed . 
 appropriate therapy was established , and the patient was discharged after 42 days of treatment in complete remission .