Primary cutaneous cryptococcosis in a patient with minimal change nephrotic syndrome

Sir,

Cryptococcosis is the infectious disease that usually affects the respiratory tract and subsequently disseminates to other organs such as the central nervous system, the urinary tract, etc. Cryptococcosis is frequently found in immunosuppressed patients, especially HIV positive patients (~2–10% of AIDS patients). Approximately 15% of the patients with systemic dissemination of cryptococcosis have secondary involvement of the skin. However, primary cutaneous cryptococcosis (PCC) without systemic infection is a rare clinical event [1]. We report a case of PCC in a patient with minimal change nephrotic syndrome (MCNS).

A 26-year-old Japanese man was admitted to our hospital in September 2004 because of high fever, cellulitis and cutaneous nodules of his legs. In January 2004, he was diagnosed as having a nephrotic syndrome and a renal biopsy was performed. A renal biopsy specimen showed almost normal glomeruli without any depositions when subjected to immunofluorescent staining, compatible with MCNS. Treatment with 60 mg of prednisolone daily was started after diagnosis of MCNS. Because proteinuria continued, treatment with 50 mg of azathioprine daily was added in August 2004 and, 2 weeks later, cutaneous nodules of the right lower leg occurred. Although he received antibiotics in another hospital, his cutaneous lesions gradually enlarged.

At admission, a physical examination showed cellulitis, nodules and aedema of both legs. Urinalysis revealed massive proteinuria (8.7 g/day) without haematuria. Lymphocyte counts were 330/mm3. Serum total protein, albumin and total cholesterol were 4.4 g/dl, 2.2 g/dl and 441 mg/dl, respectively. Blood urea nitrogen and creatinine were 28 mg/dl and 0.8 mg/dl, and IgG, IgA and IgM were 196 mg/dl, 113 mg/dl and 118 mg/dl, respectively. Creatinine clearance was 125.8 ml/min and the selectivity index was 0.069. Examination of cerebrospinal fluid showed no abnormalities. The anti-HIV antibody test was negative. Cryptococcus neoformans antigen in serum was positive (titre: 32768x) without other evidence of systemic infection. A chest X-ray showed no abnormalities. The biopsy specimen of a skin lesion showed an inflammatory infiltration, containing PAS-positive micro-organisms (Figure 1) and subsequently the positive diagnosis of PCC was made.



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Fig. 1. Graft angiography. With hand compression of the proximal upper arm, the course of the feeding artery (black arrow) and AVG (white arrow) were identified. The prime brachial artery was also shown (asterisk).

 
In the present case, the dosage of prednisolone was tapered to 30 mg daily and azathioprine was stopped. Treatment with intravenous fluconazole was started and the skin lesions resolved approximately 3 months later. The nephrotic syndrome was ameliorated by the long-term steroid therapy, and both the titre of IgG and the lymphocyte counts subsequently normalized. To date, relapse of PCC and the systemic dissemination of cryptococcosis have not been seen in the ambulatory patient.

In 10–15% of patients with disseminated cyptococcosis, secondary cryptococcal skin lesions are found. However, previous reports had described that PCC is an extremely rare disease, especially if AIDS patients [1] or organ transplant recipients receiving immunosuppressive therapy [2,3] are excluded. Cryptococcus neoformans is an encapsulated yeast in the environment worldwide and frequently causes pulmonary cryptococcosis and/or cryptococcal meningitis, which could become terminal events. To our knowledge, however, the present patient is the first case of PCC in a patient with MCNS, unrelated to HIV and transplantation. Disseminated cryptococcosis is often seen in HIV positive patients and typically occurs when the CD4 cell counts are significantly decreased [4]. On the other hand, a previous report described that the CD4 cell counts also decrease in patients with MCNS [5]. Furthermore, the total lymphocyte counts in the present case were reduced by immunosuppressive therapies. Recently, the combination therapy of steroids and immunosuppressive agents is frequently used to treat massive proteinuria in patients with a nephrotic syndrome, especially steroid-resistant nephrotic syndrome. These therapies, however, often cause an immunocompromized host and can be associated with several subsequent infectious diseases. In patients with suspected T-cell dysfunction, PCC should be considered and a skin biopsy should be performed to make the differential diagnosis, including PCC, of all atypical and local cutaneous lesions.

Conflict of interest statement. None declared.

Naoko Ogami1, Taro Horino1, Kaoru Arii1, Toshihiro Takao1, Kozo Hashimoto1, Masahiro Seike2 and Hajime Kodama2

1 Department of Endocrinology, Metabolism and Nephrology2 Department of Dermatology Kochi Medical School Kohasu Okoh-cho Nankoku Kochi 783-8505 Japan Email: horinot{at}med.kochi-u.ac.jp

References

  1. Bellosta M, Gaviglio MR, Mosconi M et al. Primary cutaneous cryptococcosis in an HIV-negative patient. Eur J Dermatol 1999; 9: 224–226[ISI][Medline]
  2. Baumgarten KL, Valentine VG, Garcia-Diaz JB. Primary cutaneous cryptococcosis in a lung transplant recipient. South Med J 2004; 97: 692–695[ISI][Medline]
  3. Gupta RK, Khan ZU, Nampoory MRN et al. Cutaneous cryptococcosis in a diabetic renal transplant recipient. J Med Microbiol 2004; 53: 445–449[Abstract/Free Full Text]
  4. Werchniak AE, Baughman RD. Primary cutaneous cryptococcosis in an elderly man. Clin Exp Dermatol 2004; 29: 159–160[CrossRef][ISI][Medline]
  5. Fiser RT, Arnold WC, Charlton RK et al. T-lymphocyte subsets in nephrotic syndrome. Kidney Int 1991; 40: 913–916[ISI][Medline]




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