Skeletal hyperostosis and extraosseous calcification in patients receiving long-term etretinate (Tigason)

In an ongoing study of patients on long-term etretinate (Tigason) therapy, 13 patients with a congenital or inherited disorder of keratinization and 10 patients with psoriasis were examined to investigate the incidence of, and the factors associated with, skeletal hyperostosis. Skeletal scintigraphy, plain radiographs, haematological and biochemical analyses were performed. Using all criteria, 7 of 13 patients with a congenital or inherited disorder of keratinization showed evidence of hyperostosis. No single investigation was able to detect all these cases; in particular, skeletal scintigraphy was positive in only nine of the 13 patients who showed hyperostosis. Eleven of the 13 patients with hyperostosis gave a history of musculoskeletal symptoms compared with three of the 10 patients without hyperostosis. There was no clear association with total dose or duration of treatment. Serum chemistry and haematological studies were normal. In two patients the 24-h urinary calcium excretion was significantly elevated, an abnormality which has not been described previously. Annual lateral thoracic spine radiographs with additional views of symptomatic areas are recommended for patients on long-term etretinate therapy.     

Granulation tissue that developed after a minor trauma in a psoriatic patient on long-term etretinate therapy

Synthetic analogues of retinoic acid, isotretinoin in particular, are known to cause granulation tissue in the nail sulcus and healing cystic acne. We observed granulation tissue that developed in a psoriatic patient on long-term oral etretinate therapy (30 mg/day for 3 years), another synthetic analogue of retinoic acid. In August of 1988, the patient, a 44-year-old male, hit his lower leg against a wooden stick, resulting in a laceration. At that time he had relatively limited patches of psoriasis, but his skin was generally thin with telangiectasia, even in areas without psoriasis, probably due to the long-term use of oral etretinate and topical steroid. In spite of treatment with topical disinfectants and oral antibiotics, the wound progressed into granulation tissue surrounded by erythema and multiple punctate erosions with marked secretion of a clear exudate. The histological findings of the granulation tissue included the presence of proliferating microvessels and a relatively dense cell infiltration with a predominance of plasma cells on the sparse edematous connective tissue. Based on these findings, the rash was considered to be retinoid-induced granulation tissue. As compared with previous reports, our case had the following characteristics: development of rash after minor trauma, rash on the lower leg, eosinophil infiltration into the rash. We believe that long-term users of oral etretinate should be cautioned about the potential for delayed wound healing and the formation of granulation tissue.     

Pulmonary toxicity in a patient with psoriasis receiving methotrexate therapy

We report a 34-year-old woman with psoriasis who developed shortness of breath during methotrexate therapy. Methotrexate had been started 4 months earlier and the patient had ingested a cumulative dose of 232 mg. Pulmonary function tests showed a reduction in transfer factor to 76% of predicted. Methotrexate was stopped and her symptoms rapidly resolved. Pulmonary function tests deteriorated further despite stopping methotrexate but with no recurrence of symptoms with a transfer factor of 66% of predicted 2 months later. At 5 months after stopping methotrexate the patient remained well and pulmonary function had improved with a transfer factor of 79% of predicted. Pulmonary toxicity is a rare but important adverse effect of methotrexate therapy in patients with psoriasis.     

Thrombocytopenia possibly induced by etretinate in a psoriatic patient

A patient with psoriasis vulgaris developed multiple purpura on the extremities and hemorrhage at the oral mucosa and gingiva with marked thrombocytopenia. This thrombocytopenia was possibly induced by a retinoid agent, etretinate, from the clinical course and data. The total amount of etretinate administered was 2,410 mg over 191 days (41.9 mg/kg body weight, average 15.3 mg/day). A platelet transfusion partially restored the platelet count and the purpura and gingival hemorrhage disappeared approximately 10 days after the cessation of etretinate. However, the platelet count remains at 60-80 x 103/mm3 after two and a half years without etretinate therapy. Although there are only a few case reports of etretinate-induced thrombocytopenia, we should pay more attention to the peripheral platelet count during etretinate therapy.     

Retrospective radiographic study of skeletal changes after long-term etretinate therapy

Radiographic skeletal examinations were performed in eight adult patients who had received the aromatic retinoid etretinate for various disorders of keratinization over periods ranging from 1 to 7 years. Age- and sex-matched controls were also examined. In all patients, alterations of ossification were found to a varying degree, including calcification of the anterior spinal ligament, vertebral hyperostoses at the anterosuperior and anteroinferior margins of the vertebral bodies, unilateral bridging of vertebral bodies, hyperostoses of the calcanei at the insertion of the plantar ligament and bone accretion at the anterolateral lips of the acetabula. All the bone changes were asymptomatic. Serum calcium, inorganic phosphate, alkaline phosphatase, calcitonin and parathormone were within normal physiological ranges. In general, the bone changes observed after long-term etretinate treatment closely resembled the effects of isotretinoin on the skeleton.     

Serial liver biopsies in psoriatic patients receiving long-term etretinate

Twenty psoriatic patients treated with etretinate have been followed in a prospective study of liver biopsies. Twelve patients were followed up for 3 years, with four liver biopsies each. No significant damage to the liver was found during etretinate therapy. Etretinate may be stored in the fatty tissues of the liver or other body areas for prolonged periods.     

Blistering, erosions and scarring in a patient on etretinate

A case is reported of a patient who developed blistering of the skin followed by ulceration and scarring while on treatment with etretinate.     

Cutaneous infection due to Cladophialophora bantiana in a patient receiving immunosuppressive therapy

Cladophialophora bantiana (Xylohypha bantiana. Cladosporium trichoides). a dematiaceous fungus, causes mainly infections of the central nervous system. Systemic antifungal therapy is apparently unsuccessful. Extracerebral involvement is uncommon and only few cases have been reported. We describe a 63-year-old patient, a kidney transplant recipient on prolonged prednisone and cyclosporin, who developed a large single lesion on the thigh from which Cladophialophora bantiana was cultured. A 3-month course of itraconazole 200 mg daily resulted in complete healing of the lesion. To the best of our knowledge this is the first report on cutaneous infection with Cladophialophora bantiana in an organ transplant recipient and the first in whom treatment with itraconazole led to resolution.     

Generalized pustular psoriasis in a child: observation of long-term combination therapy with etretinate and calcipotriol for 16 years

Generalized pustular psoriasis (GPP) is a rare condition in young children. It is difficult to treat and may require long-term systemic therapy. We report the long-term course of a 3-year-old boy whose onset of psoriasis dated to age 7 months. He was treated with etretinate and psoralen plus ultraviolet A therapy initially and then with etretinate alone, and at age 12, topical calcipotriol was added. At the age of 19, he had been taking oral retinoids for 16 years, with a mean dose of etretinate of 0.22 mg/kg per day, a total amount of approximately 37 g, without evidence of stunted growth, ligamentous calcification, hyperostosis, or hepatic toxicity.     

Exacerbation of porokeratosis during etretinate therapy

Four patients with disseminated superficial porokeratosis (DSP) were treated with the oral aromatic retinoid etretinate. Using the standard dosage of 1 mg/kg/day, 3 patients showed exacerbation of cutaneous lesions 4-6 weeks after initiation of treatment. Because of additional severe generalized itching and discomfort in all patients, treatment had to be discontinued. The clinical exacerbation correlated with a significant increase in the lymphohistiocytic dermal infiltrate beneath the cornoid lamella. In our experience the use of etretinate triggered the exacerbation of porokeratotic lesions with associated side effects showing that their use is not necessarily of benefit as previously reported.