chronic granulomatous disease - Europe PMC

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Nov 16, 1989 - In summary, we have reported a case of Ehlers-Danlos syndrome where bruising has been a prominent and troublesome feature, and in whom ...
Journal of the Royal Society of Medicine Volume 83 December 1990

of type X EDS proved particularly instructive as a specific biochemical defect was identified to account for both the connective tissue and the platelet abnormalities, namely fibronectin deficiency. A number of haematological abnormalities have been reported in association with EDS including clotting factor deficiencies"2, capillary fragility3, platelet ultrastructural abnormalities4, and platelet aggregation abnormalities5. Abnormalities in the platelet aggregating properties of collagen in patients with EDS has also been reported6. There has, however, been no large series of patients, as yet, with EDS who have been investigated as regards underlying platelet or clotting abnormalities and the reports that exist do not identify any consistent defect. In summary, we have reported a case of Ehlers-Danlos syndrome where bruising has been a prominent and troublesome feature, and in whom no underlying haematological abnormality was detected.

Atypical X-linked variant of chronic granulomatous disease

A G McT Wilson MRCP1 D D Munro MD FRCP' J A Walker-Smith MD FACP2 Departments of 'Skin and 2Paediatric Gastroenterology, St Bartholomew's Hospital, West Smithfield, London EClA 7BE Keywords: chronic granulomatous disease; atypical variant

Classical X-linked recessive chronic granulomatous disease (CGD) causes recurrent severe infections in childhood. The rare atypical X-linked and autosomal recessive forms may be milder and the diagnosis overlooked. The case of a boy with an atypical variant of CGD is described.

Case report The patient is a 7-year-old Greek-Cypriot boy of nonconsanguineous parents. He presented at 3 weeks of age with bloody diarrhoea. Small pustules were present on the lower abdomen and an ulcer on the scrotum. Three months later

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References 1 Gamba G, Gatti V, Longoni P, Grignani G, et al. Type IV EhlersDanlos syndrome and factor IX deficiency. A case report. Haematologica 1986;71:139-41 2 Lisker R, Nogueron A, Sanches-Medal L. Plasma thromboplastin component deficiency in the Ehlers-Danlos syndrome. Ann Intern Med 1960;53:388-95 3 Barabas GM, Barabas AP. The Ehlers-Danlos syndrome. Oral and haematological findings in 9 cases. Br Dent J 1967:473-9 4 Kashiwagi H, Riddle JM, Abraham JP, Frame B. Functional and ultrastructural abnormalities of platelets in Ehlers-Danlos syndrome. Ann Intern Med 1965;63:249-54 5 Estes JW. Platelet abnormalities in heritable diseases of connective tissue; Conf. New York Acad. Sci on platelets and their role in haematosis. Ann NY Acad Sci 1971;201:445-50 6 Hedner U, Nilsson IM. Platelet aggregating properties of Ehlers-Danlos syndrome 'collagen'. Thrombos Diathes Haemorrh 1975;33:380-1 (Accepted 27 March 1990)

he developed a perianal abscess which was successfully treated with antibiotics. Colonoscopy and biopsy showed nonspecific colitis. Allergic colitis was suspected and he was given sulphasalazine and a proprietary milk-substitute. He subsequently underwent a milk-challenge without adverse effect. He continued to have intermittent diarrhoea and on one occasion Clostridium difficile was grown from his faeces. He had persistent mouth ulcers, episodes of cervical lymphadenitis, balanitis, and indolent rusted granulomatous nodules most recently on the left cheek (Figure 1). There is no history of unusual or recurrent infection in the patient's parents or his two elder sisters. The infective episodes were treated with repeated courses of oral flucloxacillin and have resolved satisfactorily. Investigations confirmed mild anaemia on occasions (minimum Hb 9.0 g/dl, Hb electrophoresis normal). His C-reactive protein (CRP) was elevated and reflected the activity of his colitis (maximum CRP 68 mg/l). Immunoglobulin levels were normal. The nitroblue tetrazolium test (NBT) was performed and was only weakly positive (NBT 0-4%), and superoxide production was detectable although greatly reduced (Table 1). The nearly normal amount of cytochromeb245 implies a variant form of CGD. The intermediate amount of superoxide production in his mother suggests an X-linked mode of inheritance.

Case presented to Section of Dermatology, 16 November 1989

Discussion CGD is an inherited disorder of neutrophil function, in which phagocytosis is normal but in which there is a deficiency of the enzymes responsible for the burst of oxidative metabolism required to kill the ingested organisms. A defect in any part of the electron transport chain from glucose to nicotinamide adenine dinucleotide phosphate (NADPH), and then to a flavoprotein, then onto cytochromeb-245, and finally onto oxygen will result in reduced 2- production and failure to kill certain ingested organisms'.

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Table 1. Superoxide production and cytochromeb concentration in the patient and his mother (courtesy of Professor A W Segal)

Superoxide (02-) production

Cytochromeb-245

in response to PMA (nmol/min per 107 PMN)

(by spectroscopy) (pmoI/107 PMN)

Patient 4.2 Mother 46.5 Normal range 100-200

Figure 1. Crusted abscess overlying left zygoma

74.4 129.6 100+20

PMA, Phorbol myristate acetate; PMN, polymorphonuclear neutrophil leucocyte

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Journal of the Royal Society of Medicine Volume 83 December 1990

CGD is now classified according to mode of inheritance and amount of cytochrome present2. The largest CGD subgroup is the classical X-linked recessive form (type I) in which cytochromebm4S is completely absent and there is no detectable superoxide production. Foci of recurrent chronic infection develop in the skin, respiratory tract, lymph nodes, liver and bone provoking a granulomatous reaction with abscess and sinus formation3. A presentation mimicking Crohn's disease has also been described4. The causative organisms are catalase-negative, commonly Staphylococcus aureus, but also Serratia, Candida albicanu and Aspergillus. Unless treated with intensive antibiotics, death in early childhood is the usual outcome. Prophylactic co-trimoxazole has been shown to increase the infection-free periods3 but bone-marrow transplantation offers the only possible 'cure'. The heterozygous carriers of the defective X-chromosome have intermediate amounts of the cytochrome. Mothers of affected boys may also exhibit a lupus erythematous-like syndrome5. A male patient with detectable superoxide production and X-linked inheritance has been described6, however the cytochrome was later found to be absent implying a type I variant. Types II and Im are autosomal recessive forms with normal amounts of and absent cytochrome respectively. Our patient's presumed X-linked CGD with normal cytochromeb_20 suggests he is an extremely rare type IV variant. A similar case with minimal superoxide production but with a positive NBT test has been investigated by Borregaard et aL7. The clinical course was dominated by recurrent suppurative lymphadenitis but also included

encealitis, hepatomegaly and fevers. The precise molecular defect in this group is unknown. Complementation studies of hybrid cells are needed to confirm its genetic exclusivity from other groups. Recurrent skin infection with abscess formation in lymph nodes, liver or lung occurring in either sex especially with a family history of recurrent or unusual infection, should alert the clinician to the possibility of CGD.

References 1 Segal AW. Variations on a theme of chronic granulomatous disease. Lancet 1985;i:1378-83 2 Curnutte JT. Classification of chronic granulomatous disease. Hematol Oncol Clin North Am 1988;2:241-52 3 Forrest CB, Forehand JR, Axtell RA, et aL Clinical features and current management of chronic granulomatous disease. Hematol Oncol Clin North Am 1988;2:253-66 4 Isaacs D, Wright VM, Shaw DG, et aL Chronic granulomatous disease mimicking Crohn's disease. J Pediatr Gastroenterol Nutr 1985;4:498-501 5 Schaller J. Illness resembling lupus erythematosus in mothers of boys with chronic granulomatous disease. Ann Intern Med 1972;76:747-50 6 Lew PD, Southwick FS, Stossel TP, et aL A variant of chronic granulomatous disease: deficient oxidative metabolism due to lowaffinity NADPH-oxidase. N Engi J Med 1981;306:1329-33 7 Borregaard N, Cross AR, Herlin T, et aL A variant form of X-inked chronic granulomatous disease with normal nitroblue tetrasolium slide test and cytochrome b. Ewr J Clin Invest 1987;13:243-7 (Accepted 18 April 1990)

Surgical treatment for Crohn's disease of the fourth part of the duodenum

R Orda MD MS J SayfanmD Y CarmeliMD E Scapa MD Departments of Surgery 'A' and Gastroenterology, Assaf Harofeh Medical Centre, Sackler Faculty of Medicine, Tel Aviv University, Zerifin 70300, Israel Keywords: Crohn's disease; duodenum, fourth part

Crohn's disease of the duodenum is an uncommon condition occurring in 0.5-4% of patients with Crohn's disease' Mot of the cases occur in the first and second parts, obstruction being the main indication for operation. Involvement of the fourth part is very rare presenting in only about 10% ofcases with Crohn's disease of the duodenum4. To the best of our knowledge the surgical treatment for strictures ofthe distal part ofthe duodenum has not been specifically discussed in the literature. Case report A 43-year-old man was admitted with signs and symptoms of upper gastrointestinal obstruction, consisting mainly of vomiting of 6 weeks' duration. There was a 10-year history of Crohn's ileitis. A barium meal study performed 7 years ago revaled a fixed tubular segment of duodenal narrowing at the fourth portion, and another shing sign at the terminal ileum. The patient was afebrile, with a non-tender, distended abdomen and normal bowel sounds. The nasogastric

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