Novel cases of blastomycosis acquired in Toronto, Ontario.

Blastomycosis a potentially fatal fungal disease, is well known from defined areas of endemicity in Ontario, primarily in the northern part of the province. We present 2 unusual cases that appear to extend the area of endemicity into urban southern Ontario, specifically Toronto. Both patients presented to a dermatology clinic with skin lesions. Chest radiography, history and general physical evaluation indicated no disease at other body sites. Both cases appeared to represent "inoculation blastomycosis" connected with minor gardening injuries and a cat scratch respectively. Atypical dissemination could not be completely excluded in either case. Neither patient had travelled recently to a known area of high endemicity for blastomycosis, nor had the cat that was involved in one of the cases. Physicians must become aware that blastomycosis may mimic other diseases, including dermal infections, and may occur in patients whose travel histories would not normally suggest this infection.

Sarcoidosis presenting as nail dystrophy.

A 45-year-old woman was referred to the dermatology clinic for assessment of "refractory onychogryphosis." She had a 3-year history of lesions involving distal phalanges of the first and third of her left foot. Initially she described periungual erythema and swelling. Three weeks later she noted a whitish growth and thickening of her third toenail. X-ray films of the digit were reported as normal. Several months later the same changes occurred in her great toe. These lesions were asymptomatic. There was no history of trauma. Numerous fungal cultures were negative. No light microscopic examinations were undertaken. She had a trial of both topical and systemic terbinafine of 3-months duration with no clinical improvement. Several clinical opinions were obtained from two dermatologists, a surgeon, and a chiropodist. Past medical history of note was significant for tubal ligation, cervical cancer, and chronic sinusitis. The latter condition in retrospect was thought to be secondary to sarcoidosis. Physical examination revealed periungual violaceous discolouration of the first and third toes of the left foot. There was evidence of significant nail changes including dystrophy, onycholysis, and hyperkeratosis (Fig. 1). The fingernails were normal. There were no other skin abnormalities. A punch biopsy of the tip of the third toe showed granulomatous inflammation. There was evidence of hyperkeratosis, exocytosis, and a dense infiltrate composed of collections of histiocytes and a few giant cells forming granulomas (Fig. 2). Repeat x-ray films of the foot showed soft tissue swelling of the first and third digits. There was bony resorption in the distal phalanges with a lacey trabecular pattern compatible with sarcoidosis (Fig. 3). Chest x-ray films revealed marked hilar adenopathy. The patient was sent to a respirologist who concurred with the diagnosis of sarcoidosis. Further investigations included a low serum calcium of 2.07 mmol/L, serum ACE of 70 U/L (upper limit of normal is 75), Wintrobe erythrocyte sedimentation rate (ESR) of 10 mm per hour, thyroid stimulating hormone concentration of 0.65 mU/L, and a urinary calcium excretion rate that was elevated at 7.3 mmol/day. Pulmonary function tests were unremarkable. The patient was initially treated with clobetasol under occlusion and intralesional triamcinolone with minimal improvement. She was subsequently started on prednisone, 15 mg per os daily because of the lung and bone involvement with significant improvement noted in the toe lesions with diminution of both the swelling and violaceous discolouration.

Steady-state pharmacokinetics of isotretinoin and its 4-oxo metabolite: implications for fetal safety.

Isotretinoin is the most potent human teratogen on the market. Women for whom contraception fails may conceive during or soon after discontinuing isotretinoin therapy, making its elimination kinetics a crucial determinant of fetal safety. The steady-state pharmacokinetics of isotretinoin and its major 4-oxo metabolite were studied in 16 adult patients treated for acne who were receiving doses that ranged from 0.47 to 1.7 mg/kg daily. This is the first study of the pharmacokinetics of isotretinoin in women of childbearing age (n = 11). The clinical efficacy and tolerability of isotretinoin was investigated, and the correlation between these data and steady-state serum concentrations of isotretinoin was tested. The concentration-time data best fitted a two-compartment open model with linear elimination. There was no correlation between efficacy and tolerability of isotretinoin and steady-state serum concentrations. There was no correlation between dose of isotretinoin and steady-state concentration, due to the large variability in apparent clearance. Values for elimination half-life (t1/2) of isotretinoin and its metabolite were 29+/-40 hours and 22+/-10 hours, respectively. These data suggest a longer elimination t1/2 of the parent drug than previously reported. This is probably due to the longer sampling time used in this study (as long as 28 days). This study suggests that a greater variability exists in the safe time after discontinuation of the drug for onset of conception.

The risks of systemic corticosteroid use.

Because of their potent antiinflammatory and immunosuppressive properties, systemic corticosteroids are used to modify a vast array of diseases. This class of drugs, however, has the potential to produce multiple adverse effects presenting the dermatologist with difficult decisions in the management of patients with potentially steroid responsive disorders. This article reviews the side effects of systemic corticosteroids, comments on strategies to minimize these side effects, as well as, outlining suggested mechanisms by which physicians may minimize the risks of medical legal consequences owing to adverse reactions to these drugs.

Isotretinoin and tetracycline in the management of severe nodulocystic acne.

Thirty patients with treatment-resistant cystic and conglobulate acne entered a randomized double-blind protocol, testing the efficacy of isotretinoin versus tetracycline. After 16 weeks of isotretinoin treatment, the mean number of cysts decreased by 64% and the mean sum of the longest diameters was reduced by 68%. After 16 weeks of tetracycline therapy, the total number of cysts showed a mean decrease of 52%, and the mean sum of the longest diameters decreased by 60%. The reduction in the number of cysts and the sum of their longest diameters that occurred after 16 weeks of treatment was statistically significant for each of the treatment groups, but there was no statistically significant difference between the treatment groups at the end of therapy. Eight weeks after the discontinuation of treatment in the isotretinoin group, there was an overall reduction from baseline of 82% in the cyst count and 88% in the sum of the longest diameters. In the tetracycline treatment group, the overall reduction from baseline in the cyst count was 54% and in the sum of the longest diameters, 60%. This led to a statistically significant difference in the two treatment groups at 24 weeks. All patients on isotretinoin experienced side effects that were primarily related to the integumentary system but necessitated discontinuation of the drug for a short period of time in only one patient. Long-term follow-up, 8 months after discontinuation of the study, showed a prolonged significant remission of acne in the isotretinoin group but not in the tetracycline group.

Blastomycosis: a new endemic focus in Canada.

A survey of the 38 patients resident in Ontario from whose sputum, body fluids or tissues Blastomyces dermatitidis was cultured by our laboratory between 1970 and 1981 revealed a new endemic focus to the north and east of Lake Superior, where 20 of 27 traceable patients lived. Direct microscopy revealed B. dermatitidis in 90% of the cases. A lack of clinical awareness, however, had often resulted in a delay (average 15 weeks) in diagnosis. In two cases the disease was identified only at autopsy. About 80% of the patients survived.

Sacroiliitis in severe psoriasis.

In 100 consecutive patients admitted to the hospital for control of severe psoriasis, 25 had radiologic changes characteristic of psoriatic arthritis. Twenty had erosions and mild sclerosis around the sacroiliac joint; in eight of these, asymptomatic sacroiliac changes were the sole manifestation of musculoskeletal disease. Twelve had vertebral syndesmophytes, 11 had terminal interphalangeal joint changes, and 10 had peripheral joint involvement.

Psoriatic arthritis in severe psoriasis.

SUMMARY: Of 100 patients admitted to hospital for treatment of psoriasis, 32 had clinical or radiologic evidence of psoriatic arthritis and 17 had both types of evidence. Eight had radiologic evidence of spinal or sarroiliac involvement without symptoms and seven had clinical evidence of peripheral arthritis without radiologic evidence. Patients with psoriatic sacroilitis and spondylitis were most likely to have typical radiograpic changes. It was concluded that psoriatic arthritis is common in patients with severe psoriasis and that is associated with more extensive skin disease than is found in patients without arthritis.