Sequential occurrence of Graves' disease and immune thrombocytopenic purpura as manifestations of immune reconstitution inflammatory syndrome in an HIV-infected patient.

Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients after initiating antiretroviral therapy usually involves worsening manifestations of overt infectious disease. Here, we describe a sporadic case of a late-diagnosed HIV-positive man who developed Graves' disease as the first noninfectious IRIS followed by immune thrombocytopenic purpura as the second noninfectious IRIS.

Rates of Serious Infections in HIV-Infected Patients Receiving Tumor Necrosis Factor Inhibitor Therapy for Concomitant Autoimmune Diseases.

OBJECTIVE: To estimate the incidence of serious infections in patients with HIV infection and autoimmune disease who were treated with tumor necrosis factor (TNF) inhibitors, and to compare these rates by stratified viral load levels. METHODS: Using a unified search strategy, 4 centers identified HIV-infected patients exposed to TNF inhibitors. Patient characteristics and infection data were assessed via chart review in all patients who were ≥18 years old and who received TNF inhibitor therapy after HIV diagnosis, between January 1999 and March 2015. RESULTS: We studied 23 patients with 26 uses of TNF inhibitor therapy (86.7 person-years of followup). Two (8.7%) experienced at least 1 serious infection episode, for an overall incidence rate of 2.55 per 100 patient-years (95% confidence interval [95% CI] 0.28-9.23). The incidence rate per 100 patient-years was 3.28 (95% CI 0.04-18.26) among patients with a viral load >500 copies/ml at therapy initiation and 2.09 (0.03-11.65) among patients with a viral load ≤500 copies/ml. CONCLUSION: This study suggests that the rate of serious infections in patients with HIV infection under active care who have received treatment with TNF inhibitors may be comparable to the rates observed in registry databases.

Nerve abscess in Hansen's disease as part of immune reconstitution inflammatory syndrome: a case report.

Immune reconstitution inflammatory syndrome is an inflammatory reaction in HIV-infected patients after initiation of antiretroviral therapy resulting from restored immunity to specific infectious or non-infectious antigens. A 36-year-old male patient on highly active antiretroviral therapy of six months duration, presented with reddish, tender lesions over medial aspect of arm and a single, anaesthetic patch. Tender fluctuant swellings were seen on the medial aspect of left forearm. A few of them had ruptured spontaneously discharging pus. A skin biopsy from the anaesthetic patch showed caseating epitheloid granulomas. A diagnosis of Hansen's disease borderline tuberculoid in type 1 reversal reaction, with formation of nerve abscess due to Immune Reconstitution Inflammatory Syndrome was made. The patient was started on multibacillary multidrug therapy as per WHO guidelines and highly active antiretroviral therapy was continued.

Tuberculoid leprosy and cytomegalovirus retinitis as immune restoration disease in a patient with AIDS.

Here we report a unique case of tuberculoid leprosy and cytomegalovirus retinitis in a 27-year-old female patient with AIDS, suggestive of highly active antiretroviral therapy (HAART)-induced immune restoration disease. After initiation of HAART, the patient presented with decreased visual acuity, hypoesthetic patch with local nerve thickening, and an increase in her CD4+ T cell count. On further investigations cytomegalovirus retinitis and tuberculoid leprosy were confirmed. To our knowledge no case with such a co-existence has previously been reported.

Unmasking tuberculosis in the era of antiretroviral treatment.

Tuberculosis (TB) can develop soon after antiretroviral treatment initiation, as the result of restoration of the anti-TB specific immune response. This form of the disease is often defined as "unmasked TB", and it represents a major challenge for severely immune-suppressed HIV-infected subjects initiating treatment. Emergence of previously unrecognised TB disease occurs frequently in countries where TB/HIV co-infection is common, and where antiretroviral treatment has become increasingly accessible. The challenges posed by unmasked TB, such as its high incidence, the lack of reliable diagnostic tools and the uncertainties on its optimal management, may hamper our ability to face the TB/HIV epidemic. Therefore, unmasked TB appears a major threat to global health and poses additional barriers to successful HIV/AIDS care and treatment programmes. This review focuses on the epidemiology, immunopathogenesis and clinical manifestations of unmasked TB, and provides evidence-based recommendations for management and care of the disease.

Immune reconstitution inflammatory syndrome in leprosy.

Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical deterioration in the clinical status of a patient infected with human immunodeficiency virus (HIV) on highly active antiretroviral treatment (HAART). The immune suppression caused by the virus can initially suppress the clinical manifestations of leprosy which can then be unmasked after treatment with HAART or an inflammatory reaction can occur in the initial months of therapy, resulting from dysregulated recovery of immunity to specific antigens. Both these conditions are identified as IRIS in leprosy. Though this syndrome is a widely recognized entity presently, there is still a lack of universally acceptable diagnostic criteria for the condition. The first case published case of leprosy- associated immune reconstitution disease was reported in 2003 and about 47 confirmed cases of IRIS in leprosy have been reported since then, mostly from Brazil and India. Anti-inflammatory drugs and steroids are the drugs of choice in inflammatory episodes with continuation of antiretroviral therapy. With increasing affordability of antiretroviral therapy, clinicians will put more and more number of human immunodeficiency virus infected patients on therapy and hence an increase in the incidence of IRIS is expected. Therefore, it is important to understand all facets of this syndrome which is becoming more prevalent with each passing day.

Type 2 lepra reaction with HIV1 co-infection: a case report with interesting management implications.

A patient co-infected with leprosy and Human Immunodeficiency Virus (HIV)-type 1 who developed type 2 lepra reaction in the absence of antiretroviral therapy is presented. The reaction responded only after initiating anti retroviral therapy (ART) despite normal CD4+ counts. The present report suggests that type 2 reactions in leprosy and HIV co-infected patients may not always be the typical manifestation of immune reconstitution inflammatory syndrome (IRIS) and stresses the importance of considering concomitant HIV infection in refractory lepra reactions. Extensive research is required into the manifestations of HIV in leprosy patients.

Drug-induced uveitis in aids patients: two case reports.

Patients with acquired immunodeficiency syndrome (AIDS) can develop severe uveitis. Although infectious and autoimmune causes must always be considered, drug induced uveitis is also an important etiology. Herein, we present two case reports illustrating the classical presentation of rifabutin and cidofovir induced uveitis. The first case was a 33 year old woman with AIDS treated with anti-protease and anti-tuberculosis drugs (including rifabutin). She presented with a red painful right eye. There was a strong anterior segment inflammation with fibrinous exudates and a dense vitritis. Rifabutin was stopped and topical steroids and mydriatics were given. Intraocular inflammation and symptoms rapidly resolved. The second patient was a 36 year old woman who presented with a painful decrease of vision in her left eye. She was followed for bilateral CMV retinitis in the setting of AIDS and had recently received 2 systemic injections of cidofovir. Anterior segment inflammation with posterior synechiae in both eyes and folds of Descemet membrane in the left eye were noted. Intraocular pressure was 0 mmHg in the left eye and 10 mmHg in the right eye. Fundus examination disclosed CMV retinitis scars in the right eye and choroidal folds in the macula of the left eye. Cidofovir was discontinued and topical steroids and mydriatics started. Progressively the inflammation decreased and the intraocular pressure returned to normal levels. In conclusion, rifabutin and cidofovir are classical examples of drug induced uveitis with distinct characteristic clinical presentation. Recognition of those entities in AIDS patients can avoid useless and potentially invasive interventions in those fragile people.

Skin infections in HIV-infected individuals in the era of HAART.

PURPOSE OF REVIEW: Clinicians should be aware of the shift in the cutaneous infectious disease burden in human immunodeficiency virus-infected individuals as a reflection of immune restoration in the era of highly active antiretroviral therapy (HAART). RECENT FINDINGS: As in the general population but to greater extent, methicillin-resistant Staphylococcus aureus (MRSA) soft-tissue infection is a rising problem among those with human immunodeficiency virus (HIV). Human papilloma virus (HPV) is exceedingly prevalent and persistent despite HAART, and HPV-associated malignancy is increasing as those with HIV live longer. Herpes, syphilis, and Kaposi's sarcoma continue to plague individuals with HIV. Immune reconstitution inflammatory syndrome (IRIS) is common and often presents with infectious cutaneous manifestations. SUMMARY: This review implicates the importance of the acknowledgment of MRSA infections risk factors, screening for HPV-related neoplasia, continuance of trials to establish the efficacy of herpes vaccines, and awareness of prevalent cutaneous infections presenting with IRIS in those with HIV.

Central nervous system disorders after starting antiretroviral therapy in South Africa.

OBJECTIVE: To describe the spectrum of central nervous system (CNS) disease during the first year of antiretroviral therapy (ART) and to determine the contribution of neurological immune reconstitution inflammatory syndrome (IRIS). DESIGN: A prospective observational cohort study conducted over a 12-month period at a public sector referral hospital in South Africa. METHODS: HIV-seropositive patients who developed new or recurrent neurological or psychiatric symptom(s) or sign(s) within the first year of starting ART were enrolled. We used the number of patients starting ART in the referral area in the preceding year as the denominator to calculate the incidence of referral for neurological deterioration. Patients with delirium and peripheral neuropathy were excluded. Outcome at 6 months was recorded. RESULTS: Seventy-five patients were enrolled. The median nadir CD4(+) cell counts was 64 cells/µl. Fifty-nine percent of the patients were receiving antituberculosis treatment. The incidence of referral for CNS deterioration in the first year of ART was 23.3 cases [95% confidence interval (CI), 18.3-29.2] per 1000 patient-years at risk. CNS tuberculosis (n = 27, 36%), cryptococcal meningitis (n = 18, 24%), intracerebral space occupying lesions (other than tuberculoma) (n = 10, 13%) and psychosis (n = 9, 12%) were the most frequent diagnoses. Paradoxical neurological IRIS was diagnosed in 21 patients (28%), related to tuberculosis in 16 and cryptococcosis in five. At 6 months, 23% of the patients had died and 20% were lost to follow-up. CONCLUSION: Opportunistic infections, notably tuberculosis and cryptococcosis, were the most frequent causes for neurological deterioration after starting ART. Neurological IRIS occurred in over a quarter of patients.

Pancreatitis de repetición en paciente con infección por el virus de la inmunodeficiencia humana en tratamiento antirretroviral / Recurrent pancreatitis in a human immunodeficiency virus-infected patient on antiretroviral therapy

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Human papillomavirus in the era of highly active antiretroviral therapy for human immunodeficiency virus: an immune reconstitution-associated disease?

Human immunodeficiency virus (HIV)-related cutaneous and anogenital disease in the highly active antiretroviral therapy (HAART) era presents challenging problems for dermatologists. Immune reconstitution-associated diseases (IRADs) are common and important consequences of HAART. Dermatologists should be aware of the cutaneous manifestations of IRAD. The prevalence of clinical human papillomavirus (HPV)-related disease is increased in HIV and does not appear to be diminished by HAART. Many patients on HAART are dogged by persistent cutaneous warts. Anogenital precancer is also common in HIV and may be burgeoning with HAART. Clinicians should be aware of the increased risk of cervical, penile and vulval/vaginal cancers in treated and untreated patients with HIV. The increase in HPV infection in HIV-infected individuals may be, at least partly, due to increased exposure to diverse HPV types, particularly high-risk types that might be able to persist for longer in anogenital regions. Alternatively, persistent/emergent HPV disease in HIV infection might represent persistent or modulated immunodysregulation after HAART and be viewed as a form of IRAD. The immunopathogenesis of HPV IRAD is fascinating and possibly determined by host genotype.

Immune reconstitution inflammatory syndrome due to Mycobacterium bovis Bacillus Calmette-Guerin in infants receiving highly active antiretroviral therapy: a call for universal perinatal rapid HIV testing prior to administration of BCG immunization of neonates.

The evidence behind the World Health Organization guidelines that BCG vaccination should not be used in HIV-infected children is compelling. We report three cases of severe BCG-associated immune reconstitution syndrome in HIV-infected infants and describe measures available in developing countries that prevent inadvertent BCG immunization in these infants.

Key data from the 11th International Workshop on Adverse Drug Reactions and Co-Morbidities in HIV.

The effectiveness of current antiretroviral therapies has led to more patients receiving long-term therapy, and increasing numbers of older patients. The complex interactions between HIV infection, ageing, comorbid conditions and drug-related toxicities, and their combined effects on patient health and quality of life, were the subject of the 11th International Workshop on Adverse Drug Reactions and Co-Morbidities in HIV. Key topics included the metabolic effects of antiretroviral agents, cardiovascular disease, bone metabolism and age-related changes in disease and response to drug therapy. Data presented at the meeting reflect the growing recognition of common pathways that contribute to progression of mutiple types of disease and adverse drug reactions.

Immune reconstitution inflammatory syndrome among HIV-infected South African infants initiating antiretroviral therapy.

OBJECTIVES: To determine the incidence, clinical manifestations and risk factors for immune reconstitution inflammatory syndrome (IRIS) in young children initiating highly active antiretroviral therapy (HAART). DESIGN: A prospective cohort of antiretroviral-naïve HIV-infected children less than 24 months of age enrolled in a treatment strategies trial in Johannesburg, South Africa. METHODS: Among 169 HIV-infected children initiating HAART, April 2005 to November 2006, the records of 83 children suspected to have IRIS within 6 months of starting treatment were reviewed to determine whether they met criteria for IRIS. Seven were excluded due to incomplete follow-up. Pretreatment and post-treatment characteristics of children with and without IRIS were compared. RESULTS: Overall, 34/162 (21%) children developed IRIS at a median of 16 days (range 7-115 days) post-HAART initiation. Bacille Calmette-Guérin reaction was most common occurring in 24/34 (71%) children, primarily injection site lesions and/or ipsilateral axillary lymphadenitis with abscess. Other IRIS conditions (not mutually exclusive) included Mycobacterium tuberculosis (n = 12), cytomegalovirus pneumonia (n = 1), Streptococcus pneumonia sepsis (n = 1), and severe seborrheic dermatitis (n = 1). Children with IRIS were younger (median age 7 vs. 10 months, P = 0.007) with a lower CD4 cell percentage (median 13.9 vs. 19.2, P = 0.009) at HAART initiation than controls. After 24 weeks on HAART, 62% of IRIS cases vs. 28% of controls had HIV RNA more than 400 copies/ml (P = 0.001), odds ratio = 2.88 (95% confidence interval = 1.14-7.29) after adjusting for baseline factors. CONCLUSION: Infants and young children with advanced HIV disease initiating HAART are at high risk for developing IRIS, leading to additional morbidity and possibly impairing virologic response to antiretroviral treatment.

Acetyl-l-carnitine and nucleoside reverse transcriptase inhibitor-associated neuropathy in HIV infection.

OBJECTIVES: Antiretroviral toxic neuropathy (ATN) is associated with dideoxynucleoside reverse transcriptase inhibitor use in patients infected with HIV, possibly as a result of mitochondrial toxicity. Acetyl-l-carnitine (ALC) has been linked to symptomatic improvement in ATN. We present an open-label single-arm pilot study to evaluate changes in intra-epidermal nerve fibre (IENF) density and mitochondrial DNA (mtDNA) copies/cell among subjects treated with 3000 mg ALC daily. METHODS: Punch skin biopsies were examined at baseline and after 24 weeks of therapy. Participants reported neuropathic symptoms using the Gracely Pain Intensity Score. Neurological examinations were completed. RESULTS: Twenty-one subjects completed the study. ALC was generally well tolerated. The IENF density did not change in cases completing 24 weeks of ALC therapy, with median (90% confidence interval) IENF changes of -1.70 (-3.50, infinity) (P=0.98) and 2.15 (-0.10, infinity) (P=0.11) for the distal leg and proximal thigh, respectively. Fat mtDNA copies/cell did not change with therapy. Improvements in neuropathic pain (P<0.01), paresthesias (P=0.01), and symptoms of numbness (P<0.01) were noted. Similarly, improvement was noted on the Gracely Pain Intensity Score. CONCLUSIONS: ALC therapy coincided with improvements in subjective measures of pain in this open-label single-arm study. However, changes were not observed in objective measures of IENF density or mtDNA levels, providing little objective support for use of ALC in this setting.