Faculty Bibliography

A 55-year-old woman with melasma develops biopsy-proved exogenous ochronosis in the setting of prolonged topical hydroquinone use. A limited number of similar reports exist in the US literature and are the basis for an FDA call to review hydroquinone-based products. This case underscores the difficult therapeutic dilemma which this diagnosis presents to dermatologists

Solitary fibrous tumor is an uncommon mesenchymal neoplasm that can arise in both pleural and extrapleural locations. Composed of spindled cells intimately admixed with collagen bundles arranged in a 'patternless pattern,' this heterogeneous tumor can mimic a variety of benign and malignant mesenchymal neoplasms. We present the histological and immunohistochemical findings of two primary cutaneous solitary fibrous tumors, discuss the differential diagnosis, and review the literature. Although solitary fibrous tumors in cutaneous and subcutaneous regions are extremely rare, it should be considered in the differential diagnosis of primary spindle cell neoplasms of the skin

Neutrophilic eccrine hidradenitis typically manifests as erythematous plaques on the face, trunk, or extremities. This eruption has been associated with numerous factors, but most commonly is seen with chemotherapy, particularly cytarabine. We report a 73-year-old woman with acute myelogenous leukemia who developed rapidly expansive neutrophilic eccrine hidradenitis mimicking facial cellulitis only after a course of cytarabine was followed by granulocyte-colony stimulating factor. Prompt diagnosis is imperative to prevent prolonged antimicrobial therapy

BACKGROUND: Polyoma BK virus produces an aggressively destructive nephropathy in approximately 3% to 8% of renal allografts, is associated with graft loss within one year in 35% to 67% of those infected and there is no therapy of proven efficacy. Leflunomide is an immune suppressive drug with anti viral activity in vitro and in animals. METHODS: We treated twenty-six patients with biopsy proven NK virus nephropathy (BKN) with either leflunomide alone (n=17) or leflunomide plus a course of cidofovir (n=9) and followed them for six to forty months. Leflunomide was dosed to a targeted blood level of active metabolite, A77 1726, of 50 microg/ml to 100 microg/ml (150 microM to 300 microM). Response to treatment was gauged by serial determinations of viral load in blood and urine (PCR), serum creatinine, and repeat allograft biopsy. RESULTS: In the 22 patients consistently sustaining the targeted blood levels of active drug, blood and urine viral load levels uniformly decreased over time (P<.001). Mean serum creatinine levels stabilized over the first six months of treatment, and with 12 months or more of follow-up in 16 patients the mean serum creatinine has not changed significantly from base line. Four patients who did not consistently have blood levels of active drug (A77 1726) above 40 microg/ml did not clear the virus until these levels were attained or cidofovir was added. CONCLUSIONS: Leflunomide inhibits Polyoma virus replication in vitro and closely monitored leflunomide therapy with specifically targeted blood levels appears to be a safe and effective treatment for Polyoma BK nephropathy.

Fabry disease is a rare X-linked recessive lysosomal storage disease. Patients typically have angiokeratomas distributed between the umbilicus and knees, painful crises of the hands and feet, and renal, ophthalmologic, and cardiac abnormalities. An 11-year-old boy presented with a 6-year history of widespread petechial-like lesions and painful crises of the hands and feet. On physical examination, he had numerous erythematous, nonblanching pinpoint macules and rare papules with an overlying crust. These lesions were widely distributed on his trunk, palms, and soles, while sparing the area between the umbilicus and knees. Histologic evaluation of one of these lesions found several dilated, blood-filled vessels in the upper dermis beneath a thinned epidermis. The patient also had markedly decreased alpha galactosidase A levels. Although the distribution of the angiokeratomas was atypical, the clinical and histologic findings were consistent with a diagnosis of Fabry disease

Intestinal resection (IR) may lead to hyperoxaluria and nephrolithiasis. A rat model of IR was developed, in which kidney stones form. We describe the urine chemistries and histopathologic features. Rats underwent resection of 40-45 cm of distal ileum (n=16) or sham resection (SR) (n=8), and were then fed a 1% Na oxalate, 0.02% Ca diet. After 1 week on the diet, 24 h urine samples were obtained for stone chemistries. At 4-7 months after surgery, kidneys were examined grossly and by light microscopy. The extent and location of crystallization was assessed by polarized light. Histochemistry and infrared spectroscopy were used to determine crystal composition. IR rats had higher urine oxalate excretion (P<0.01) and concentration (P<0.001) than SR rats, and lower urine citrate excretion; only IR rats formed kidney stones (12/15 surviving rats). Tissue calcification was found only in kidneys from IR rats, located in the cortex (83% of kidneys), medulla (73%) and papillary tip (47%). Crystals, composed of CaOx, apatite, and calcium carbonate, filled collecting duct lumens, and were associated with tubular obstruction, and interstitial inflammation. Crystals in the papillary interstitium incited inflammation with tubular destruction and development of progressive papillary erosion. This new rat model of nephrolithiasis and nephrocalcinosis resembles the pattern of urinary abnormalities and tissue calcification that may be seen in humans with small bowel resection. The model allows further studies of the mechanisms of renal crystal formation, and possible therapeutic interventions.