Case Studies

 Case 3.10 Autosomal recessive chronic granulomatous disease

Julie was 34y old when she was referred to the nutritional unit because of very severe weight loss and a history of inflammatory disease in several organ systems. At the age of 3 yr, she had a severe chest infection caused by aspergillus. A further episode occurred at 11 yr and a CT scan showed diffuse pulmonary fibrosis. An open lung biopsy at the referral hospital was reported as showing non-caseating granulomas attributed to extrinsic allergic alveolitis.

During teenage years, she remained generally unwell but with no specific focal illnesses until she was 23 years old, when after holiday work as a waitress in the Mediterranean, she presented with chronic diarrhoea and an ESR of 48 mm/hr. She had lost nearly 8 Kg in weight and a rectal biopsy showed non caseating epithelioid and giant cell granulomas attributed to Crohn's disease. Her liver function shown raised serum globulins and a raised serum alkaline phosphatase of 187 iu/l (NR 20-85). A liver biopsy revealed portal tract infiltration with mononuclear cells, no hepatic fibrosis but many well-defined epithelioid granulomas in the hepatic lobules, a picture thought to be consistent with primary biliary cirrhoses, although her serum antimitochrondrial antibodies (see Chapter 14.8.2) had been negative on multiple occasions. Despite oral corticosteroid therapy, she continued to lose weight and the possibility of intestinal tuberculosis was raised. A further 3 month therapeutic trial of anti- tuberculous was of no significant benefit.

At the age of 34 yrs, she had been admitted to hospital with a swinging pyrexia and further weight loss and her sputum had been positive for aspergillus fumigatus on three occasions. On referral, her chest X-ray showed total consolidation of her right lung with a large abscess cavity. Aspiration of the lung abscess under CT guidance grew aspergillus fumigatus but, despite intravenous Amphotericin B and oral Itraconazole, her condition deteriorated.

Because of her history of a systemic granulomatous disease involving lung, gut and liver, immunological investigations were finally performed (Table). The complete absence of the ability to generate a respiratory burst in the NBT test confirmed the diagnosis of chronic granulomatous disease and, because of her gender, this was considered to be of autosomal recessive inheritance. Subsequent studies showed her deficient in the P47 phox component of NADPH oxidase, the most common form of autosomal recessive CGD.

Despite intensive therapy, including transfusions of normal granulocytes, she developed respiratory failure and died in intensive care.