Q J Med 2000; 93: 559-560
© 2000 Association of Physicians
Correspondence |
Thymoma, autoimmunity and fatal immunodeficiency
Department of Medicine, Frenchay Hospital, Bristol Department of Medicine Department of Immunology, Southmead Hospital, Bristol
Sir,
A 47-year-old male presented to us in 1995 with diarrhoea, weight loss, lichen planus, oesophageal candidiasis and streptococcal pneumonia. HIV serology and PCR tests were negative. Lymphocyte subset analysis confirmed normal T-cell numbers, but absence of CD 19+ B lymphocytes. Severe pan-hypogammaglobulinaemia was confirmed (IgG, IgA, IgM 1.6 g/l, 0.2 g/l, and 0.15 g/l, respectively). The differential diagnosis included haematological malignancy, and primary immunodeficiency. Good's syndrome (thymoma and hypogammaglobulinaemia) was suspected and confirmed by CT scans of the mediastinum. A spindle cell thymoma was excised in May 1995. Intravenous immunoglobulin (0.4 g/kg/month) as infection prophylaxis began pre-operatively. The haemoglobin immediately post thymectomy was 11.8 g/dl. Six weeks later, he was readmitted as a medical emergency with dyspnoea and hypoxia. The haemoglobin was now only 2.6 g/dl (white cell count 13.6x10-9, platelets 873). After resuscitation with transfused blood, investigations including bone-marrow trephine suggested autoimmune erythrocyte aplasia. Oral prednisolone proved ineffective, but within 4 weeks of starting cyclosporin A, he was transfusion-independent.
By September 1996, after several bacterial chest infections, he had CT confirmed bronchiectasis and had become increasingly frail. New problems included severe anorexia, dysphagia, and vomiting. Gastroscopy showed a severe pan-gastritis (Figure 1
) with a normal oesophagus and duodenum. Malignancy or occult infection was suspected. Multiple biopsies showed granulation tissue, but no gastric epithelium. There were no malignant features. Special stains for bacteria, mycobacteria, H. pylori, and fungi were negative. Specific immunostaining for Cytomegalovirus (CMV) was strongly positive. Ganciclovir (5 mg/kg b.d.) was commenced. He spent the next 12 months in hospital and survived Pneumocystis carinii pneumonia (PCP). Serial gastric biopsies confirmed continuing mucosal damage and CMV persistence, despite repeated courses of anti-CMV therapy in the form of Ganciclovir, Forscarnet, combination therapy with both, and Cidofovir. He required TPN, opiates for epigastric pain, and ultimately a feeding jejunostomy. He continued to deteriorate, and in September 1997, complained of acute abdominal pain and constipation. There was no clinical evidence of obstruction. He deteriorated rapidly and died. At post-mortem, the submucosa of the whole intestine was distended with clear gas-filled vesicles suggestive of pneumatosis intestinalis, but with no evidence of perforation. No gas-forming organisms were identified on microscopy or culture. The cause of death was presumed to be sepsis.
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The association of thymoma with hypogammaglobulinaemia is rare but well recognized, particularly in this age group. Immunoglobulin deficiency may precede or follow thymectomy. The pathogenesis is poorly understood. Paradoxically, 40% of patients with a thymoma have an associated autoimmune syndrome.1 Pure erythrocyte aplasia is believed to be autoimmune and may respond to immunosuppression,2 cyclosporin A being the treatment of choice in those unresponsive to steroids. It too is rare, and like hypogammaglobulinaemia, should prompt suspicion of thymoma. Onset of erythrocyte aplasia after thymectomy, although described,1 is extremely rare. CMV infection of the gastrointestinal tract occurs in severely immunocompromised individuals. In this case, there were additional pointers to severe T-cell dysfunction, including mucocutaneous candidiasis and PCP. Yet T-cell numbers and subsets were normal, and tests of T-cell function prior to cyclosporin, including responses to PHA were normal. Cyclosporin A would have further compromised T-cell function. Blood transfusion may have infected the patient with CMV. We feel justified in assuming that the severe gastritis was directly due to CMV disease, in that pathological abnormalities were demonstrated in a subject who had symptoms of disease at this site.3,4 Pneumatosis intestinalis is an uncommon condition also associated with CMV infection.5
The case described is a striking example of how immunodeficiency and autoimmunity can coexist. Immunosuppressive treatment may be unavoidable, but the risk is further immunocompromise. HIV-like syndromes can arise in association with thymoma. General physicians and specialists alike should carefully investigate immunosuppressed patients with symptoms suggestive of GI disease for opportunistic infections, not forgetting CMV.
References
1. Erslev AJ, Soltan A. Pure red-cell aplasia: a review. Blood1996; 10:20–8.
2. Rosenow EC, Hurley BT. Disorders of the Thymus. A Review. Arch Intern Med1984; 144:763–70.[Abstract]
3.
Goodgame WR. Gastrointestinal Cytomegalovirus Disease. Ann Intern Med1993; 119:924–35
4. Buckner SF, Pomery C. Cytomegalovirus disease of the gastrointestinal tract in patients without AIDS. Clin Infect Dis1993; 17:644–56.[ISI][Medline]
5.
Bohler A, Speich R, Russi EW, et al. Pneumatosis intestinalis after active cytomegaloviral infection after lung transplantation. Chest1995; 107:582–3.
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