Non-cryptosporidial diarrhoea in human immunodeficiency virus (HIV) infected patients.

Thirty of 81 consecutive HIV antibody positive patients referred with non-cryptosporidial diarrhoea had no potential infectious cause; most had AIDS related complex rather than the full blown syndrome. Opportunistic infections with cytomegalovirus (CMV), mycobacterium avium-intracellulare (MAI), and herpes simplex virus (HSV), which allowed a diagnosis of AIDS to be made, were found in 19 patients and were the presenting features of AIDS in five. Other potential pathogenic species included entamoeba, giardia, campylobacter, and salmonella (without septicaemia). Cytomegalovirus infection was often accompanied by abdominal pain. Severe weight loss (greater than 10 kg) at presentation was found in patients with CMV infection and MAI. Bloody diarrhoea was confined to the group with HSV procitis. Malignant causes of diarrhoea were rare. Two patients developed a squamous carcinoma of the anorectal margin and one a non-Hodgkin's lymphoma. In only two of 12 patients who had Kaposi's sarcoma was this considered as a cause of diarrhoea. Rigid sigmoidoscopy showed macroscopic abnormalities in over a third (32) of the 81 patients with non-cryptosporidial diarrhoea. Most commonly this was severe inflammation (17) or discrete ulceration (four) [three of whom had CMV colitis]. Kaposi's sarcoma was identified in 11 patients. Non-specific inflammation was seen histologically in 40 of the 60 patients with no sigmoidoscopic inflammatory changes. Barium enema only revealed an abnormality in a minority of the patients and a colonoscopy only revealed information additional to rigid sigmoidoscopy in two patients--one with CMV ulcers in the transverse colon and the other with evidence of Kaposi's sarcoma not seen in the rectum. Ten patients had a rectal biopsy examined by electron microscopy as no infective cause of diarrhoea was uncovered. In four of these microtubular structures which are commonly seen in viral infections were found and two had prelymphomatous changes and in one of these frank lymphoma has developed. We recommend multiple stool analysis, sigmoidoscopy and rectal biopsy as the initial investigations in these patients reserving tests of malabsorption, colonoscopy, and barium enema for the small number of more difficult cases.     

Opportunistic infection complicating acquired immune deficiency syndrome. Clinical features of 25 cases

Twenty-five cases of acquired immune deficiency syndrome (AIDS) complicated by opportunistic infections were diagnosed at Lenox Hill Hospital during an 18 month period and followed for at least 1 year or until the patients' deaths. Twenty-three patients were homosexual men, including 1 i.v. drug user, and 2 were heterosexual i.v. drug users, including the sole woman. Seventy infections were diagnosed. The commonest etiologic agents included Candida albicans, Pneumocystis carinii, cytomegalovirus, and Mycobacterium avium-intracellulare. Less frequent pathogens included Cryptococcus neoformans, Toxoplasma gondii, Cryptosporidium, JC virus, Mycobacterium xenopi, and Mycobacterium tuberculosis. Seven men also had Kaposi's sarcoma. Prodromal symptoms lasted up to 8 months before the diagnosis of AIDS. Immunologic and serologic evaluation demonstrated lymphopenia, polyclonal hypergammaglobulinemia, cutaneous anergy, reversal of the T-cell helper/suppressor ratio, and serologic evidence of previous exposure to CMV, EBV, and HBV. Pneumocystis pneumonia was diagnosed during life in 17 patients, by transbronchial biopsy and bronchoscopic washings, and all 17 cases were successfully treated. However, pneumocystis was more refractory to treatment than previously described and required an average of 29 days of antimicrobial therapy. Disseminated infections with atypical mycobacteria and cytomegalovirus were the leading causes of death. Bone marrow aspirates and biopsies often revealed a cellular abnormality (82%) but only occasionally yielded an infectious diagnosis (32%). However, bone marrow examinations were the major means of detecting atypical mycobacteriosis. Colonoscopic biopsies were most useful for establishing the presence of cytomegalovirus colitis. Transbronchial biopsies and bronchial washings gave a high yield of opportunistic pathogens including 34 infectious diagnoses confirmed by 31 procedures. Multiple site biopsies and close communication between the clinician and the pathologist were needed for early diagnosis of opportunistic infections. Twenty-two patients (88%) died, and the few survivors remain debilitated.     

No news is good news: opportunistic infections

The 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) was notable for not having any oral sessions on opportunistic infections. This is an indication of the enormous success of combination antiretroviral therapy, which has greatly reduced the occurrences of opportunistic infections. Hepatitis C was discussed at the conference, but it was treated as a co-morbid condition rather than an opportunistic infection. Two studies addressed the question of stopping pneumocystis prophylaxis in patients responding to antiretroviral therapy. Other issues discussed included mycobacterium avium complex (MAC), cytomegalovirus (CMV), and pyogenic bacterial infections.     

Unusual presentation of cytomegalovirus enteritis after liver and kidney transplantation

Cytomegalovirus (CMV) is a cause of significant morbidity and mortality in solid organ transplant recipients. Gastrointestinal (GI) tract infection by CMV in this population can cause symptomatic disease, which typically manifests as fever, abdominal pain, nausea, and bloody diarrhea. Erosive lesions of the GI mucosa are often evident on endoscopic exam. We report an unusual presentation of CMV enteritis in a kidney and liver transplant recipient with the development of acute onset voluminous watery diarrhea in the absence of other typical symptoms and subsequent progression to hypovolemic shock and acute renal failure. This case emphasizes the atypical presentations of common opportunistic infections that may occur in immunosuppressed hosts.     

Splenectomy in patients with AIDS

To establish the indications for splenectomy in patients with human immunodeficiency virus (HIV) infection we retrospectively analyzed 12 patients who underwent splenectomy. Patients with HIV infection who had immune thrombocytopenic purpura (ITP) were excluded as they had no splenomegaly and a definite indication for splenectomy exists in some of these patients. All 12 patients were anemic; 6 were thrombocytopenic and 6 leukopenic. All patients had splenomegaly and all were febrile. At surgery 3 patients were found to have Mycobacterium avium intracellulare (MAI) infection; 2 had splenic abscess due to Salmonella group D; 1 each had cytomegalovirus (CMV) splenitis and localized Kaposi's sarcoma (KS) of the spleen. No definite histopathologic diagnosis could be made in five patients, all of whom had evidence of extramedullary hematopoiesis. The degree of splenic enlargement did not correlate with the outcome. Both clinical and hematologic improvements were achieved in patients with splenic abscess and in patients who had splenomegaly, anemia, and thrombocytopenia. The presence of either of these findings constitutes an indication for splenectomy. Anemia and/or leukopenia without thrombocytopenia failed to improve; the presence of MAI and active CMV infection also resulted in failure. The presence of either of these conditions may be considered a contraindication to splenectomy.     

The prevalence of skin disease in HIV infection

The frequency of skin problems in patients with HIV infection and AIDS is well known from clinical experience and from the reports of cohorts of patients followed over months and years. Decreased mucocutaneous immunity often accounts for the earliest clinical signs seen in HIV-infected patients. As HIV disease progresses, these skin manifestations may become more severe and varied. In advanced immunosuppression, opportunistic pathogens may present as atypical cutaneous lesions. The following two cases illustrate a number of important points in relation to the management of skin disease in HIV patients.     

Cytomegalovirus infection

The pathogenic importance of cytomegalovirus (CMV) infection in AIDS-associated pneumonitis is controversial. Uncertainty regarding the significance of CMV isolation from pulmonary secretions of AIDS patients results in part from the difficulty in distinguishing CMV infection from CMV disease and from the high frequency of pulmonary CMV co-infection with other opportunistic pathogens. From our review of the literature to date, we have found only three cases in which AIDS patients with hypoxemia and infiltrates on chest x-ray had lung biopsy or autopsy material reported to demonstrate CMV cytopathic effect in the absence of any other pathogen. However, pulmonary CMV co-infection may be a marker of poor outcome in Pneumocystis carinii pneumonia. In this article, appropriate criteria for instituting specific therapy with the antiviral drug ganciclovir are described.     

Infections in patients with immunodeficiency with thymoma (Good syndrome). Report of 5 cases and review of the literature

Immunodeficiency with thymoma (Good syndrome, GS) is a rare, adult-onset condition that is characterized by thymoma, hypogammaglobulinemia, and low numbers of peripheral B cells. CD4+ T lymphopenia and an inverted CD4:CD8+ T-cell ratio may be present. Here we report 5 patients with GS and infectious complications who were seen at 3 institutions between 1983 and 1999. Three patients had recurrent sinopulmonary infections, 3 had severe cytomegalovirus (CMV) disease, and 1 had Pneumocystis carinii pneumonia. Review of the literature identified 46 other reports of infections in GS patients. The infections reported in all 51 patients included recurrent sinopulmonary infection (19 cases with documented respiratory pathogens), generally with encapsulated bacteria, most often Haemophilus influenzae (11 cases); CMV disease (5 cases); bacteremia (7 cases); oral or esophageal candidiasis (6 cases); persistent mucocutaneous candidiasis (5 cases); chronic diarrhea (5 cases with documented stool pathogens); urinary tract infections (4 cases); P. carinii pneumonia (3 cases); tuberculosis (2 cases); Kaposi sarcoma (1 case); disseminated varicella (1 case); candidemia (1 case); wound infection with Clostridium perfringens (1 case); Mycoplasma arthritis (1 case); and other infections. Patients with GS present with a spectrum of sinopulmonary infections and pathogens similar to common variable immunodeficiency (CVID). Compared with patients with CVID, opportunistic infections, including severe CMV disease, P. carinii pneumonia, and mucocutaneous candidiasis, appear to be more common in patients with GS, and patients with GS may have a worse prognosis. GS should be ruled out in patients with thymoma or CVID who develop severe, especially opportunistic, infections. Treatment with intravenous immune globulin is recommended for all patients with GS.     

Late onset CMV disease presenting as a colonic stricture in a liver transplant recipient

Cytomegalovirus (CMV) is a common opportunistic infection in solid organ transplant (SOT) recipients in the first 6 months after transplant. Late onset CMV infection or disease outside the classical risk period is uncommon and can present with atypical signs and symptoms. Here, we report a case of late onset CMV presenting as a colonic stricture more than 10 years after liver transplantation in the absence of traditional CMV risk factors. We also briefly review CMV colitis presenting as a mass or stricture in SOT recipients.     

Gastrointestinal cytomegalovirus manifestations in AIDS

Cytomegalovirus (CMV) infection is one of the most important intestinal opportunistic infections in AIDS. In severe cases ulcerations and colitis are the commonest manifestations. 184 HIV positive patients with gastrointestinal symptoms were investigated by endoscopy of the gastrointestinal tract. While culture, immunohistochemical staining and histology from biopsies were performed, the results of all three methods were compared. In one third the cases CMV associated lesions could be found by endoscopy. Erosions or ulcerations are the most frequent tissue lesions. In 95% the culture was positive. In addition, immunohistochemical staining in 75% and histology in 61.7% were positive in patients with more serious manifestations. For early diagnosis endoscopy of the gastrointestinal tract and histological, histochemical and microbiological investigations of biopsies are essential.     

Perforation of the colon associated with cytomegalovirus infection

Cytomegalovirus (CMV) inclusions were found at colonic perforation sites in three patients with clinical settings suggesting a compromised immunologic status. This could be interpreted as: (1) CMV was an etiologic agent in these perforations; or (2) CMV was an opportunistic superinfection in areas of preexisting inflammation. To determine which interpretation was more likely, we examined material from these three and ten similar patients with colonic perforations, identifying any potential causative factors present. Eleven of the 13 patients had an identifiable cause of perforation, either tumor, diverticulitis, arteritis, or pancreatic pseudocyst, while two remained unexplained. If the presence of CMV merely represented an opportunistic superinfection, then all 13 should have been at equal risk of infection. However, CMV was present in only one of the 11 cases with another identifiable cause of perforation but was present in both of the cases without another cause. This is consistent with the hypothesis that CMV was in fact an etiologic or contributing factor in those cases where it was present. Other cases of CMV infection of the gastrointestinal tract were studied to determine the mechanism by which this infection could lead to perforation of a viscus. In our three cases with perforation, four additional cases of CMV infection of the colon which we have studied, and 30 other cases in the literature, CMV inclusions were found only in areas of ulceration or perforation, never in undamaged mucosa. Thus there is as yet no evidence that CMV can be a primary cause of colonic mucosal injury. It remains likely, however, that a mucosal injury due to another cause may be followed by CMV infection of the granulation tissue which then may lead to further injury and perforation.     

Kaposi's sarcoma of the bronchial tree in a renal transplant recipient

An unusual case of disseminated Kaposi's sarcoma with endobronchial lesions is presented; these localizations are quite uncommon in the course of the disease, particularly in kidney transplant recipients. Some of the multifactorial etiologies of Kaposi's sarcoma are present: immunosuppression, ethnic origin and CMV infection. We emphasize that the diagnosis of bronchial involvement can be made during fiberoptic bronchoscopy and confirmed by biopsy without excessive complications.     

Mycobacterial disease associated with HIV infection

Mycobacterial disease is a major part of the spectrum of opportunistic infections (OIs) associated with HIV infection.Mycobacterium avium intracellulare (MAI) andMycobacterium tuberculosis are the most common mycobacterial pathogens afflicting HIV-positive patients. Infection with MAI tends to be an OI of advanced AIDS, and the results of treatment are frequently unsatisfactory.M. tuberculosis tends to attack patients much earlier in the course of their HIV disease, responds to standard treatment, and is the most contagious of the life-threatening HIV-related pathogens. This article provides concise information about the management of mycobacteriosis in the context of HIV infection. It is directed especially at primary care physicians. Emphasis is on clinical manifestation, diagnosis, therapy, and prevention.     

AIDS in the pre-AIDS era

A search of the medical literature published since 1950 disclosed 19 cases of probable AIDS reported before the start of the current epidemic. These cases retrospectively met the Centers for Disease Control's surveillance definition of the syndrome and had a clinical course suggestive of AIDS. The reports originated from North America, Western Europe, Africa, and the Middle East. The mean age of patients was 37 years, and the ratio of male to female patients was 1.7:1. Sixteen patients had opportunistic infections(s) without Kaposi's sarcoma. The remainder had disseminated Kaposi's sarcoma. The commonest opportunistic infection was Pneumocystis carinii pneumonia. Two patients were reported to be homosexual. Three others had been living in Africa, and one patient was born in Haiti. In two instances concurrent or subsequent opportunistic infection occurred in family members. All patients died 1 month to 6 years after the initial manifestation of disease. In view of the historical data, unrecognized cases of AIDS appear to have occurred sporadically in the pre-AIDS era.     

Bronchoscopic and radiologic features of Kaposi's sarcoma involving the respiratory system

In a group of 61 patients admitted to New England Deaconess Hospital, Boston, with a diagnosis of acquired immune deficiency syndrome (AIDS), 25 were found to have Kaposi's sarcoma involving the skin and mucous membranes. Of these 25 patients, eight had lesions involving the respiratory system. Radiographically, patients with Kaposi's sarcoma had hilar and mediastinal adenopathy with perihilar parenchymal infiltration which progressed to diffuse bilateral infiltrates over a period of months. This pattern and the tempo of its evolution were distinctly different from the diffuse infiltrates seen in patients with Pneumocystis carinii pneumonia. Bronchoscopy was performed in seven of the eight patients, revealing characteristic lesions of Kaposi's sarcoma in the airways. We propose that parenchymal pulmonary Kaposi's sarcoma can be strongly suspected in a patient with AIDS who has the following features: a characteristic radiologic pattern; endobronchial Kaposi's sarcoma at bronchoscopy; and no evidence of opportunistic infection. In this subset of patients, further diagnostic intervention such as open lung biopsy, a procedure with potential morbidity in these ill individuals, may be unnecessary.     

Reactivation and dissemination of blastomycosis complicating hodgkin's disease: A case report and review of the literature

Patients presenting with Hodgkin's disease (HD) may show lung involvement characterized by contiguous spread from ipsilateral hilar lymph nodes. Lung consolidation or noncontiguous pulmonary involvement makes an alternative diagnosis more likely. This report describes a patient with HD in whom concurrent pulmonary blastomycosis was recognized only after chemotherapy had started and dissemination had occurred. Although Blastomyces dermatitidis may behave as an opportunitist pathogen, there are no previous reports of blastomycosis in patients with HD. Undiagnosed active opportunistic infection at the time of diagnosis of HD may complicate staging as well as treatment. Biopsy of lung lesions with stain and culture for opportunistic pathogens should be considered in patients with newly diagnosed HD disease and atypical patterns of lung involvement.     

Diagnostic yield of bronchoalveolar lavage following renal transplantation

Abstract: Organ transplant recipients are at high risk of infectious pulmonary complications. In this retrospective study, the diagnostic yield of bronchoalveolar lavage (BAL) was evaluated in renal transplant recipients. The results were analysed in special regard to the clinical presentation of pulmonary infections and the possible impact of new immunosuppressive agents. Over a 5‐year period 91 BAL were performed in 71 renal transplant recipients. Microorganisms were isolated from 69% of BAL (63/91): bacteria 32%; cytomegalovirus (CMV) 27%; Pneumocystis carinii (PC) 22%; other viruses 9% (HSV; EBV, RSV, adenovirus, HHV8); Aspergillus fumigatus 1%. Total cell counts and neutrophil counts in BAL were significantly elevated in bacterial infection, whereas BAL positive for PC showed eosinophilia (P<0.05). There was no association between clinical symptoms and the radiological pattern of infiltrates and the type of infection. Immunosuppression containing tacrolimus or mycophenolate mofetil was associated with a significantly higher percentage of PC and CMV infections compared to cyclosporin‐based immunosuppression (65% vs. 30%, P<0.005). A considerable number of PC and CMV infections occurred beyond 6 months after transplantation. In conclusion, BAL has a high diagnostic yield in renal transplant recipients. Infection with CMV and PC should also be considered beyond 6 months after transplantation, and prophylaxis for opportunistic infections should be given if the immunosuppression is intensified.     

Mycobacterial infection after renal transplantation in a Western population

Abstract:  Mycobacterial infection is a serious opportunistic infection in renal transplant recipients. The incidence is higher in developing than in developed Western countries. This study is a single-centre retrospective review of the records of 2502 renal transplant recipients in Belgium. Fourteen cases of mycobacterial infection (9 Mycobacterium tuberculosis and 5 atypical mycobacterial infection) were diagnosed. The time interval between transplantation and diagnosis was 64 ± 80 months (mean ± SD, range 5–188) for M. tuberculosis and 92 ± 75 months (range 14–209) for atypical mycobacterial infection. The localisation of M. tuberculosis was pulmonary/pleural in 67% and extrapulmonary in 33%. The atypical mycobacterial infections were located in skin, tendons, and joints. Eight patients received IV prednisolone pulse therapy for acute rejection long before the time of mycobacterial infection. The initial antimycobacterial therapy consisted of a combination of isoniazid, rifampicin, and ethambutol in all patients. In patients with M. tuberculosis infection, a good response to antimycobacterial therapy was obtained. In patients with atypical mycobacterial infection, initial treatment was successful in 3 out of 5 patients, in 1 patient recurrence was diagnosed and in another patient, who is still under treatment at present, the initial treatment was adjusted after identification of the atypical mycobacterium and its antibiogram.
The incidence of mycobacterial infection after renal transplantation did not increase with newer immunosuppressive therapy. The major risk factor is the total dose of corticosteroids. All patients responded well without major reductions in immunosuppressive therapy. Chemoprophylaxis for high-risk patients still is recommended.     

Mycobacterial disease associated with HIV infection

Mycobacterial disease is a major part of the spectrum of opportunistic infections (OIs) associated with HIV infection.Mycobacterium avium intracellulare (MAI) andMycobacterium tuberculosis are the most common mycobacterial pathogens afflicting HIV-positive patients. Infection with MAI tends to be an OI of advanced AIDS, and the results of treatment are frequently unsatisfactory.M. tuberculosis tends to attack patients much earlier in the course of their HIV disease, responds to standard treatment, and is the most contagious of the life-threatening HIV-related pathogens. This article provides concise information about the management of mycobacteriosis in the context of HIV infection. It is directed especially at primary care physicians. Emphasis is on clinical manifestation, diagnosis, therapy, and prevention. Received from the Division of Allergy and Clinical Immunology, Harbor-UCLA Medical Center, F-10, 1000 West Carson Street, Torrance, CA 90509.     

Mycobacterium avium-intracellulare pulmonary infection complicated by cutaneous leukocytoclastic vasculitis in a woman with anorexia nervosa

A 53-year-old Caucasian woman with a history of anorexia nervosa developed a bilateral lower extremity rash comprised of palpable red to violaceous, sub-centimeter papular lesions that increased in quantity rapidly. She also noted a 2-month history of non-productive cough. Imaging modalities revealed a thin-walled cavitary lesion in the right lung apex and scattered nodular opacities. Acid fast bacilli (AFB) were found in sputum and subsequently identified by culture as Mycobacterium avium-intracellulare (MAI). Punch biopsies of her skin lesions yielded a histological diagnosis of small-to-medium vessel vasculitis. Stains and cultures for organisms were negative. Her skin lesions resolved quickly after the initiation of antimicrobial therapy for MAI. Hypersensitivity vasculitis associated with an atypical mycobacterial infection is unusual. The postulated underlying mechanism is the deposit of immune complexes and not the bacillus itself. While cutaneous leukocytoclastic vasculitis (CLV) due to MAI is certainly a rare entity, it should be entertained in patients with vasculitic skin lesions and a concomitant pulmonary disease.