Gut: first published as 10.1136/gut.23.1.80 on 1 January 1982. Downloaded from Gut, 1982, 23, 80-82

Case report Chronic malabsorption due to cryptosporidiosis in a child with immunoglobulin deficiency

KS SLOPER, RR DOURMASHKIN, RB BIRD, G SLAVIN, AND A D B WEBSTER* From the Clinical Research Centre and Northwick Park Hospital, Harrow, Middlesex, and the London School ofHygiene and Tropical Medicine, London.

SUMMARY A case of fatal cryptosporidiosis in a child with primary immunoglobulin deficiency is described. This is always a serious complication in immunodeficient patients because there is no known effective therapy.

Intestinal infection by protozoan parasites collec- the next two years. Examination revealed large ton- tively called 'coccidia' is an important cause of mor- sils and a spleen which was just palpable below the tality in domesticated animals. In the past 10 years costal margin. Investigations at this time showed a there have been sporadic reports of malabsorption normal blood lymphocyte count, a neutropenia due to coccidiosis in humans. Most of these cases (neutrophils, 950/g1) and an eosinophilia (eosinophils have been associated with coccidia which were 900/,l). A five day faecal fat estimation was normal. thought to belong to the genus Isospora, and many The serum immunoglobulins were: IgG < 25, IgA < 4, http://gut.bmj.com/ of the affected patients have been on immunosup- IgM 236, and IgE < 2 units/ml. The isohaemagglutinin pressive drugs.' The taxonomy of the coccidia is now titre (anti-A) was 1:64. Delayed hypersensitivity skin better understood, and there have been a few recent tests to Candida albicans and purified protein de- reports of chronic malabsorption due to organisms rivative (PPD) were positive. In vitro lymphocyte of the genus Cryptosporidium.2 The patients so far transformation to phytohaemagglutinin was normal. reported have either been on immunosuppressive At 6 years of age he complained of chronic steator-

drugs or had primary immunodeficiency disorders. rhoea. A jejunal biopsy showed partial villous on October 1, 2021 by guest. Protected copyright. One of these patients had primary immunoglobulin atrophy. Treatment with Mepacrine, metronidazole, deficiency3 and we now report a second similar case and tetracycline did not help. At 8 years of age he where the disease was fatal. still had chronic diarrhoea and his weight and height had fallen from the 50th to the 3rd percentile during Case report the previous year. He was complaining of frequent vomiting, often associated with central abdominal This boy was born in Bermuda and was well until he pain. Investigation showed that he still had an eosi- developed septicaemia at 6 months of age. Hypo- nophilia but no longer had a neutropenia. The faecal gammaglobulinaemia was diagnosed during investi- fat was 30 g in 24 hours and he had a low serum gation of recurrent skin infections after he had calcium of 2.2 mmol/l, and a low serum folate of 38 moved to England at 31 years. He has since been ng/ml. The following tests were normal: lactose toler- maintained on weekly injections of gammaglobulin. ance test, 14C deoxycholate breath test, and serum He developed a painless swelling of the right knee at gastrin. The Lundh test showed a normal concen- 5 years of age which spontaneously improved over tration of pancreatic enzymes in the jejunal aspirate. Bacterial cultures of a jejunal aspirate grew 10' organisms/ml. There were no abnormal bile acids in *Address for correspondence: Dr A D B Webster, Division of Immunological the stools. The barium meal and follow-through were Medicine, Clinical Research Centre, Harrow, Middlesex HAl 3UJ. normal. The jejunal biopsy was reported as normal. Received for publication 23 June 1981. The liver function tests were abnormal with a raised 80 Gut: first published as 10.1136/gut.23.1.80 on 1 January 1982. Downloaded from Chronic malabsorption due to cryptosporidiosis in a child with immunoglobulin deficiency 81 serum alkaline phosphatase of 25 KA units/100 ml after this episode, although it subsequently returned. and an aspartate transaminase of 56 IU/1. Another jejunal biopsy taken during this admission During the subsequent six months he was given a showed partial villous atrophy. variety of drugs that is, Mepacrine, colistin, oxytet- Our working diagnosis at this stage was allergic racycline, metronidazole, piperazine, thiobendazole, gastroenteropathy and he was tried on various diets, ampicillin, and erythromycin but none had any effect particularly a milk-free diet, without success. His last on the malabsorption and failure to grow. A gluten- hospital admission at 12 years was for investigation free diet was also unhelpful. The diarrhoea was mar- of persistent diarrhoea, vomiting, and epigastric ginally improved by a low fat, high protein diet with pain. By now he was severely wasted with a low additional medium chain triglycerides. serum albumin, calcium, magnesium, and zinc. He He remained a sickly child, intermittently attend- was given Vivonex but four weeks later developed ing school for the next two years. At 10 years of age another episode of cholera-like diarrhoea, which he was readmitted as an emergency with severe failed to respond to hydrocortisone, gentamycin, watery diarrhoea. On examination there were signs cloxacillin, or carbenicillin. Intravenous alement- of a left lower lobe pneumonia and there was marked ation was started but seven days later he developed clubbing of the fingers and toes. The liver was en- jaundice and suddenly died of congestive cardiac larged three fingers below the right costal margin. failure. A jejunal biopsy taken a few days before There was no splenomegaly. The severity of his diar- death showed partial villous atrophy with parasites rhoea resembled cholera and he required emergency on the brush border (Figure). The necropsy findings intravenous therapy for water and electrolyte loss. suggested that the cause of death was acute pan- He was given penicillin, ampicillin, and septrin and creatitis. The jejunum had a particularly heavy in- his diarrhoea subsided after a few days. The diar- festation of coccidia, although there were many para- rhoea cleared up completely for about two weeks sites in the ileum and a few in the large bowel.

., http://gut.bmj.com/ on October 1, 2021 by guest. Protected copyright.

Figure (a) Jejunal biopsy shows degenerate epithelium at surface and in crypts in association with numerous protozoal bodies. These are seen on the cell surface and within the cytoplasm. H and E, X 600 (original magnification). (b) Electron micrograph ofjejunal biopsy. Cryptosporidium schizont, with almost mature merozoites in transverse section attached to surface ofepithelium. X 27000 (original magnification). Gut: first published as 10.1136/gut.23.1.80 on 1 January 1982. Downloaded from 82 Sloper, Dourmashkin, Bird, Slavin, and Webster Discussion was made in our case only on the sixth jejunal biopsy, although further sections taken in retrospect Four protozoal parasites collectively termed 'coc- from a jejunal biopsy a year before death showed cidia' are now known to be potentially pathogenic to typical coccidial organisms. Once diagnosed the man. These organisms are members of the sub-order prognosis is very poor, particularly if immunosup- Eimeria. The best known is Toxoplasma but Isospora pressive drugs cannot be incriminated. No satisfac- and possibly Sarcocystis can also infect the intestine tory therapy has yet been found, although of man and cause malabsorption. More recently, amprolium and other veterinary compounds are cryptosporidial infection of the small and large worth considering. Another possible approach is to bowel has been recognised in humans. Four cases give frequent infusions of the new types of intra- have so far been reported. The first was associated venous gammaglobulin which will raise the serum with an acute enterocolitis in a 3 year old child which gammaglobulin level towards normal. Now that cleared spontaneously within a few weeks without cryptosporidiosis is an established human disease, therapy.4 The second was associated with severe additional investigation is needed into the host de- watery diarrhoea in a man with bullous pemphigoid fence mechanisms against this organism in animals. being treated with cyclophosphamide and predni- There is also an urgent need to search for suitable solone.5 He improved rapidly after the immunosup- drugs that will be effective in man. pressive drugs were withdrawn. The third case had a selective IgG deficiency from infancy and developed We are grateful to the staff of the routine patho- chronic malabsorption due to Cryptosporidium at 8 logical service of Northwick Park Hospital for their years of age.3 A wide variety of drugs, including help in managing this patient. pyrimethamine, sulphadiazine, and amprolium (which is a drug used in veterinary practice) did not help (E A Steck, personal communication). This boy References still has severe malabsorption at the age of 12 years. The fourth patient was a renal transplant recipient 'Knight PK. Giardiasis, isosporiasis and balantidiasis. on immunosuppressive drugs.6 We are aware of an Clin Gastroenterol 1978; 7:31-47. additional fatal adult case in England who had nor- 2Bird RG, Smith MD, Cryptosporidiosis in Man. Parasite mal immunoglobulin levels (ADM Bryceson, per- life cycle and fine structural pathology. J Pathol 1980; 132:217-33. http://gut.bmj.com/ sonal communication). 3Lasser KH, Lewin KJ, Ryning FW. Cryptosporidial en- The host defence mechanisms against teritis in a patient with congenital hypogamma- Cryptosporidium infection are unknown, although it globulinaemia. Human Pathol 1979; 10:234-40. is likely that antibodies are involved, as two of the 4Nime FA, Burek JD, Page DL, Holscher MA, Yardley reported cases have occurred in immunoglobulin de- JH. Acute enterocolitis in a human being infected with ficient patients. Environmental factors may also play the protozoan Cryptosporidium. Gastroenterology 1976; a part and contact with infected animals or living in 70:592-6. certain parts of the world may be important. 5Meisel JL, Perera DR, Meligro BS, Rubin CE. on October 1, 2021 by guest. Protected copyright. From a practical point of view, Cryptosporidium Overwhelming watery diarrhoea associated with a Cryptosporidium in an immunosuppressed patient. infection should be considered in all patients with Gastroenterology 1976; 70:1156-60. unexplained chronic malabsorption. It should be 6Weisburger WR, Hutcheon DF, Yardley JH, Roche JC, noted that jejunal biopsy specimens may appear nor- Hillis WD, Charache P. Cryptosporidiosis in an immuno- mal, and that the small ovoid organisms can be easily suppressed renal transplant recipient with IgA deficiency. missed on histological sections. In fact, the diagnosis Am J Clin Pathol 1979; 72:473-8.