Gösta Roupe

Toxic Epidermal Necrolysis with Extensive Mucosal Erosions of the Gastrointestinal and Respiratory Tracts

Toxic epidermal necrolysis with epidermal shedding over almost the entire body occurred in a patient with classical rheumatoid arthritis treated with sulindac, penicillamine and a combination analgesic containing paracetamol and chlormezanone. Erosions in the lower respiratory tract and the intestine contributed to a lethal outcome of the disease and showed a microscopical picture similar to that of the skin involved. The histopathological picture of these extracutaneous lesions have been only briefly reported previously.

Increased urinary methylimidazoleacetic acid (MelmAA) as an indicator of systemic mastocytosis

The urinary excretion of histamine and its main metabolite, methylimidazoleacetic acid (MelmAA), was determined in 25 adult patients with the clinical diagnosis of urticaria pigmentosa (UP). Extensive clinical and laboratory investigation, including skin histology, bone marrow examination and scintigraphy of skeleton, liver and spleen, implied systemic manifestations in 16 cases. All patients with systemic mastocytosis (SM) excreted abnormal amounts of MelmAA (>4.1 mg/24 h) and most of them 8.0 mg or more per day, while histamine excretion was increased in only nine (>40 μg/24 h). Thus, the urine content of MelmAA, but not histamine, could differentiate between UP and SM. Severe pruritus was found concomitant with increased urinary MelmAA and indicated systemic mastocytosis.

Treatment of two mastocytosis patients with a histidine decarboxylase inhibitor

Alpha-fluoromethylhistidine, α-FMH (L-641.575, Merck, Sharp and Dohme), a specific irreversible inhibitor of the mammalian histidine decarboxylase, was investigated for its effect on possible histamine symptoms in mastocytosis. Two patients were treated for 28 and 22 weeks respectively. The first patient had systemic mastocytosis and a severe malabsorption causing weight loss, excessive fecal fat losses and electrolyte disturbances, the main symptom being frequent diarrhoea. The second patient had mainly skin manifestations diagnosed as urticaria pigmentosa and the main symptom was pruritus. There were no side effects of the drug. The first patient produced formed stools after one week of treatment, concomitant with a decrease in plasma histamine and in urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid (MeImAA). In the second patient definite benefit of the treatment was observed after two months. However, changes in histamine parameters occurred earlier. Plasma histamine and urinary MeImAA were reduced after one week and in two or three weeks reached a steady-state level of about 25% of pretreatment values. The results indicate an effective inhibition of histamine synthesis in both patients but only the diarrhoea seemed to be causally related to the change in histamine metabolism.

Auditory function in early syphilis A follow up study

Twenty-six patients with secondary or early latent syphilis were examined by auditory brainstem response (ABR) audiometry and by pure tone audiometry before and after treatment. Normalization was registered in four of seven patients with pathological ABR before treatment. while in three patients the ABR abnormalities remained after treatment. Thirteen patients exhibited a sensorineural hearing-loss before treatment. In two patients this hearing-loss improved after treatment and a syphilitic etiology seems plausible. The reversible lesions in the auditory system may be related to asymptomatic syphilitic meningitis. Permanent ABR abnormalities might reflect syphilitic vascular involvement in the brainstem.

Long-term follow-up of histamine turnover in mastocytosis.

To study the long-term histamine turnover in patients with mastocytosis, the urinary excretion of the main histamine metabolite tele-methylimidazoleacetic acid was measured. Eighteen patients, 10 with urticaria pigmentosa and 8 with systemic mastocytosis, were followed for several years (mean 4.2 years). Younger individuals (less than 30 years) had initially normal excretion or tended to normalize their excretion during follow-up, while older patients (greater than 30 years) often had systemic manifestations and higher excretion values, which increased in some cases during the observation period.

Suppression of T Lymphocyte Mitogen Response in Patients with Mastocytosis

Immunological functions were studied in 22 patients with mastocytosis. Lymphocyte stimulation with concanavalin A (Con A) and phytohemagglutinin showed that the patients responded with lower mitogenic activity than healthy controls. Furthermore, the lymphocytes of patients with the most extensive mast cell disease had a significantly lower Con A mitogen response than the lymphocytes of the rest of the patients. The effect of histamine and its specific metabolites, tele-methylhistamine and tele-methylimidazoleacetic acid (MeImAA), on the Con A lymphocyte mitogen response was also studied in healthy controls. Histamine had a clear suppressive effect, while the metabolite tele-methylhistamine caused only slight inhibition and MeImAA apparently had no effect. The total T cell, suppressor and helper cell numbers, measured with monoclonal antibodies, and the amount of immunoglobulins in serum were found to be normal.

HLA and lymphocyte histamine sensitivity in mastocytosis

HLA-ABC and DR typing was performed on 50 patients with mastocytosis. Lymphocyte stimulation with concanavalin A has earlier been performed in 22 of these patients. No phenotypic aberrations were detected in the patient group. 8 patients had the HLA-B12 phenotype. Lymphocytes from the HLA-B12 phenotype stimulated with a lymphocyte mitogen have earlier been shown to react with decreased inhibitory effect to histamine. 2 patients in this study had the HLA-B12 phenotype and systemic mastocytosis with high histamine turnover, but these patients reacted with a low mitogen response of the lymphocytes.

Effect of Antihistamins (H1 and H2), Cortisone and Beta-Adrenergic Stimulator on Murine Contact Sensitivity and Histamine Metabolism

A study on the influence of histamine receptor blockade, beta-adrenergic stimulation and cortisone on murine cutaneous inflammation and histamine metabolism has been performed. Cortisone was found to reduce the inflammation and urinary histamine excretion while histamine receptor blockade and beta-adrenergic stimulation did not influence the reaction. A good correlation existed between inflammation and urinary histamine excretion in all experiments. Contact sensitivity in the mouse was not found to be transferable with serum indicating that humoral antibodies play no essential role in this reaction in the mouse. On the basis of these results it is suggested that basophils might participate in murine contact sensitivity.

The Influence of Antibody on the Induction and Elicitation of Allergic Contact Dermatitis

The development of contact hypersensitivity after epicutaneous application of dinitrochlorobenzene in guinea pigs was suppressed by antidinitrophenyl γ1 and γ2 antibody which was injected locally at t

IMMEDIATE HYPERSENSITIVITY IN RABBITS FOLLOWING EPICUTANEOUS AND SUBCUTANEOUS ADMINISTRATION OF PENICILLIN

—Fourteen rabbits were exposed daily for 37 days to penicillin ointment on a croton oil damaged skin area on the upper back. Intracutaneous tests, 1 week after the sensitization was finished, resulted in immediate hypersensitivity reactions to benzylpenicilloyl polylysine (BPL) in 6 rabbits and to benzylpeniciliin in 4 rabbits. Two rabbits reacted to both test substances. Serum homocytotropic antibody was demonstrable in 2 rabbits, giving evidence that the recorded hypersensitivity reactions were due to the occurrence of such antibodies. In another group of 4 rabbits, subcutaneously sensitized with benzylpeniciliin in Freunds complete adjuvant, 1 had a very strong intracutaneous reaction to benzylpenicillin, and in its serum homocytotropic antibodies to benzylpenicillin could be demonstrated. Another of the 4 rabbits, negative to intracutaneous tests and PCA, gave a positive haemagglutination reaction.