Common Variable Immunodeficiency

A spruelike illness may occur in patients with common variable immunodeficiency (CVID). Patients with CVID have reductions in serum levels of IgG, IgA, IgM, or a combination of these. They also have poor responses to immunizations and often have recurrent infections, including sinopulmonary bacterial infections, opportunistic fungal infections, or protozoal infections. They may have seemingly paradoxical autoimmune manifestations, such as autoimmune cytopenias. Of patients with CVID, 20% have gastrointestinal manifestations (e.g., chronic giardiasis, spruelike illnesses, inflammatory bowel disease, protein-losing enteropathy, nonspecific malabsorption-like syndromes, or gastrointestinal lymphomas). Biopsy specimens of the small and large bowel may show pathological features that are indistinguishable from those of celiac disease. The diagnosis of CVID is usually made before the patient is 30 years of age.

Strongyloidiasis

The life cycle starts in the soil, where rhabditiform larvae develop into infectious filariform larvae that penetrate the skin, enter the systemic circulation, penetrate the alveolar spaces, are coughed up and swallowed, and enter the gastrointestinal tract. In the small intestine, the organism matures and releases eggs that develop into rhabditiform larvae, which are typically excreted in the stool. Autoinfection may occur, usually in immunocompromised persons, in which rhabditiform larvae mature into filariform larvae in the gut and penetrate through the wall of the large intestine or the perianal skin into the systemic circulation.

Most cases of strongyloidiasis are asymptomatic or cause only mild symptoms. An acute manifestation is duodenitis, which causes abdominal pain, nausea, vomiting, diarrhea, or a combination of these. Ground itch is a severely pruritic cutaneous manifestation of the disease. Chronic autoinfection may result in enterocolitis and malabsorption, with diffuse involvement of the upper gastrointestinal tract and the proximal large bowel. Dermal migration of the larvae may result in urticaria, a feature consistent with this patient's skin lesions, and areas of serpiginous erythema, known as larva currens. Pulmonary manifestations include dry cough and asthmalike symptoms. Rarely, a syndrome similar to Löffler's syndrome can be seen.

In this case, the recurring abdominal symptoms, the rash, and the results of examination of gastrointestinal-biopsy specimens obtained during endoscopic evaluation are consistent with a diagnosis of enterocolitis caused by strongyloides. I think it is unlikely that the patient cleared the initial infection. In addition, his low-grade fevers, weight loss, and profound malnutrition raise concern for a syndrome known as hyperinfection.

Strongyloides Hyperinfection Syndrome

Hyperinfection with S. stercoralis is the accumulation of a large burden of parasites during the autoinfection cycle. Parasites accumulate primarily in the colon, more in the right colon than in the left colon. The parasitic burden in the colon may be so high as to trigger mucosal compromise and sepsis caused by gram-negative rods. Major risk factors for hyperinfection are infection with human T-cell lymphotropic virus type I (HTLV-I) or the human immunodeficiency virus (HIV), iatrogenic immunosuppression, malignant tumors, and hypogammaglobulinemia. Eosinophilia may be absent, as it is in this case. Mortality associated with strongyloides hyperinfection is estimated to exceed 10%.

Of all the risk factors, infection with HTLV-I is the most likely in this patient, in view of his history. HTLV-I is endemic in the Caribbean, South America, southern Japan, south and central Africa, and the Middle East. Transmission typically occurs vertically from mother to child through breast-feeding but can also occur from sexual contact, blood transfusions, or intravenous drug abuse. Infection with HTLV-I promotes a type 1 helper T-cell (Th1) response (characterized by interferon-γ production and the promotion of a cellular immune response to intracellular pathogens), rather than a type 2 helper T-cell (Th2) response (characterized by the production of interleukins 4, 5, and 13 and IgE, facilitating a humoral immune response to extracellular pathogens); therefore, the host defenses against extracellular parasitic infections such as strongyloides are effectively down-regulated. For this reason, HTLV-I infection is also associated with treatment failure. Stool examination for ova and parasites can be insensitive in patients without hyperinfection, but organisms are usually detectable in patients with hyperinfection. The presence of filariform larvae and rhabditiform larvae in the stool is a clue that autoinfection has occurred, and a high parasite burden suggests hyperinfection. Serologic tests for anti-strongyloides antibodies can be helpful, but endoscopic biopsies can greatly assist in making the diagnosis. In patients with disseminated disease and pulmonary symptoms, the organism may be found in the sputum.

HBV infection and immune system role