Impaired cell mediated immunity in haemophilia in the absence of infection with human immunodeficiency virus.

Abstract

We failed to find a record ofintra-abdominal granuloma annulare lesions, and this case apyars to be the first of visceral granuloma annulare. The relation -tveen diabetes mellitus and generalised granuloma annulare has been a subject of speculation for years but remains unclear. Haim et al reported 13 patients with generalised granuloma annulare, three of whom had overt mild non-insulin dependent diabetes and seven others carbohydrate intolerance after provocative oral prednisolone.3 Other studies, however, have not confirmed this observation. A more recent report has suggested an association between granuloma annulare and insulin dependent diabetes.4 The relation between diabetes and granuloma annulare is made more complex by the histological appearance of necrobiosis lipoidica diabeticorum, granuloma annulare, and rheumatoid nodules. Each ofthese conditions includes collagen necrobiosis, and all three variants have been seen in a patient who had insulin dependent diabetes and a sister with rheumatoid arthritis.5 The histological similarities among these conditions are so great that they may share the same or a very similar pathogenesis. Immune complex deposition seems the most probable common pathway.Finally, in our patient there appeared to be a relation between diabetic control and the granuloma annulare. Poor diabetic control was associated with an exacerbation of the lesion, which in turn resulted in excessive working of the ileostomy, which was evident whatever the cause of his poor diabetic control. Biopsy sections of the skin and mesenteric nodes showed several discrete foci of connective tissue necrosis in the dermis and subcutaneous fat. The zones of necrosis were surrounded by histiocytes showing well marked palisading (figure). The histiocyte reaction was not strikingly tuberculoid. There were no giant cells, and no evidence of arteritis was detected. The cell mediated immune response was evaluated in vivo in 29 patients.twith clinically severe haemophilia by means of the dinitrochlorobenzene skin test. All patients had a response below the median normal value, and in 19.the response was on or below the lower limit of the normal range. There was no difference in skin response between patients positive and negative for the human immunodeficiency virus (HIV; formerly known as human T cell lymphotropic virus Im or lymphadenopathy associated virus). In tbe whole group, and in seronegative patients (n= 17), there was aan inverse relation between exposure to clotting factor and skin response. In seropositive patients (n= 12) no such association was apparent.This study shows that clotting factor concentrate impairs the cell mediated immune response to a new antigen in the absence of infection with HIV.

Mortality and causes of death in Dutch haemophiliacs, 1973–86

“…The administration of blood transfusion during surgery has been reported to lead to less rejections of renal transplants ( Opelz et al, 1973), and higher recurrence rates of malignan-* cies (Burrows & Tarttes, 1982), possibly caused by immunosuppression. Immune alterations have also been demonstrated in poly-transfused haemophiliacs (Brettler et al, 1986;Madhok et al, 1986). Although the role of the clotting system in metastasis is a matter of controversy (Bastida, 1985), it may well be possible that the absence of fibrin formation around microscopic tumours enhances early metastasis in haemophilia patients which, combined with immune abnormalities, raises the cancer incidence.…”

Haemophilia protects against ischaemic heart disease: a study of risk factors

“…One of the possible explanations offered was a preponderance of smokers among haemophilia patients. Other hypotheses were an effect inherent to the clotting deficiency itself or its treatment and in particular the immune alterations caused by replacement therapy (Brettler et al, 1986;Madhok et al, 1986). When current smoking and past smoking were taken together, no preponderance of smokers among haemophilia patients emerged.…”

No effect of a new second‐generation B‐domain‐deleted recombinant product on lymphocyte transformation in vitro: a study of plasma‐derived and recombinant products

“…a decline in CD4 þ cells, an increase in CD8 þ cells, impaired monocyte function and modulated cell-mediated immunity (Madhok et al, 1986(Madhok et al, , 1991Pasi & Hill, 1990;Fukutake et al, 1990;Cuthbert et al, 1992;Batchelor et al, 1992). Whether the effects are correlated to the purity of the CFCs is still a matter of controversy, but if such correlation exists, the choice of concentrate would be especially important in association with diseases affecting the immune system as well as for the development of antibodies.…”