A 24-year-old girl, born to 4th degree consanguineous parents of Turkish origin, was admitted to our hospital with complaints of pain, swelling, and limited movement of left elbow, ankles, and both knees since the age of 11 years. Following a diagnosis of juvenile idiopathic arthritis, treatment with corticosteroids, methotrexate, and sulfasalazine was given at public hospital. As she was not responding to these treatments, she was hospitalized for further examination and therapy at our University Hospital Pediatric Rheumatology Clinic 12 years ago.
Her developmental milestones were normal for age. She had cataract surgery at the age of ten. She had been diagnosed with bilaterally hand and foot onychomycosis for at least five years and received antifungal therapies with no improvement although any fungus could be identified in cultures. Her sister had been diagnosed with juvenile idiopathic arthritis at seven years of age and deceased due to chronic renal failure at the age of 13.
On her first physical examination [at first admission, her weight was 24 kg (<3 percentile) and height 132 cm (<3 percentile)] she had failure to thrive. There was limitation in left elbow dorsiflexion and in hip abduction and swelling in both knees. There was also heel pain with tenderness of achilles tendon. Besides articular findings, the most important symptoms were dystrophic nails of hand and feet with onychomycosis. Dermatologic consultation revealed that she had nail psoriasis accompanied by onychomycosis (Figure 1). According to the consultation report, there were lesions in the nail matrix (leukonychia and nail plate crumbling) and separation of the nail plate from underlying nail bed (onycholysis). Her nails were painful and were causing restrictions in her daily activities.
Laboratory examinations were as follows: white blood cells 7960/mm3 (polymorphonuclear leukocytes 56%, lymphocytes 44%), hemoglobin 10.6 g/dl, hematocrit 32.8%, platelets 392000/mm3, C-reactive protein 5 mg/dl (normal <0.5 mg/dl), erythrocyte sedimentation rate 105 mm/hr (normal <15 mm/hr), and normal renal and liver function tests. Serum immunoglobulins (Ig) were very high as compared to age matched controls (IgG 2230 mg/dl, IgM 242 mg/dl, IgA 201 mg/dl) revealing hypergammaglobulinemia. The search for anti-nuclear antibodies and rheumatoid factor was negative. Abdominal and renal ultrasonography were normal. Some of the microbiologic tests were as follows: anti-HBs (-), HbsAg(-), anti-HIV (-), Brucella agglutination test (-), CMV IgM (-), and IgG(+). Total IgE levels, eosinophil counts, absolute counts, and percentages of lymphocyte subsets and the oxidative burst activity of granulocytes were normal. She was evaluated for tuberculosis and was found to have two BCG (Bacillus Calmette-Guerin) scars, a negative tuberculin response, and a negative QuantiFERON assay result (Qiagen, Chadstone, Australia).
At the beginning of the long term follow-up (totally 12 years) she was diagnosed with refractory polyarticular juvenile idiopathic arthritis and nail psoriasis with onychomycosis. She was started on treatment with etanercept (Enbrel), methotrexate, and itraconazole with good response for a while for arthritic problems, but not for dermatologic disorders. Then, because of inadequate response, prednisolone at a dose of 1 mg/kg/day was added and also resulted in substantial improvement. She had experienced recurrent urinary tract infections and Klebsiella pneumonia was isolated from urine. Scintigraphic examinations, voiding cystography, and ultrasonography for kidneys were normal. Urine acid-fast bacilli test was negative. She did not have recurrent sinopulmonary infections.
Then, Candida albicans was isolated from swab material of nail. She was given local and systemic antifungal medications for onychomycosis with no response. As she had nail psoriasis with refractory onychomycosis, molecular genetic analyses for chronic mucocutaneous candidiasis and APECED syndrome were performed. CARD9, AIRE, and STAT1 genes were found to be wild-type.