Erin Huiras Amerson

Immune reconstitution inflammatory syndrome and tropical dermatoses.

The human immunodeficiency virus (HIV) pandemic has disproportionately affected tropical regions of the world, where dermatoses, such as leprosy and leishmaniasis, rarely encountered in temperate climates, are endemic. Although the introduction of highly active antiretroviral therapy (HAART) has been lifesaving, a few patients undergoing HAART experience clinical deterioration caused by immune reconstitution inflammatory syndrome (IRIS). This article explores the range of tropical dermatoses that are reported to date with associated IRIS events.

Accuracy of Clinical Suspicion and Pathologic Diagnosis of Kaposi Sarcoma in East Africa.

Background:HIV-associated Kaposi sarcoma (KS) is one of the most common malignancies in sub-Saharan Africa. The diagnosis is often based on clinical suspicion, without histopathologic confirmation. When biopsies are performed, the accuracy of interpretation by local pathologists is poorly understood. We assessed the accuracy of clinical suspicion and pathologic diagnosis of KS in 2 East African countries. Methods:At 2 large HIV care sites in Uganda and Kenya, we evaluated consecutive biopsies performed from October 2008 to January 2013 on HIV-infected adults with clinically suspected KS. Biopsies were interpreted by both local African pathologists and a group of US-based dermatopathologists from a high volume medical center. For the purpose of this analysis, the US-based dermatopathologist interpretation was used as the gold standard. Positive predictive value was used to characterize accuracy of local African clinical suspicion of KS, and concordance, sensitivity, and specificity were used to characterize accuracy of local pathologic diagnosis. Results:Among 1106 biopsies, the positive predictive value of clinical suspicion of KS was 77% (95% confidence interval: 74% to 79%). When KS was not histopathologically diagnosed, clinically banal conditions were found in 35%, medically significant disorders which required different therapy in 59% and life-threatening diseases in 6%. Concordance between African pathologists and US-based dermatopathologists was 69% (95% confidence interval: 66% to 72%). Sensitivity and specificity of African pathologic diagnoses were 68% and 89%, respectively. Conclusions:Among East African HIV-infected patients, we found suboptimal positive predictive value of clinical suspicion of KS and specific, but not sensitive, histopathologic interpretation. The findings call for abandonment of isolated clinical diagnosis of KS in the region and augmentation of local dermatopathologic services.

Immune Reconstitution Reactions in Human Immunodeficiency Virus–Negative Patients: Report of a Case and Review of the Literature

BACKGROUND Immune reconstitution inflammatory syndrome (IRIS) is a phenomenon initially described in patients with human immunodeficiency virus. Upon initiation of combination antiretroviral therapy, recovery of cellular immunity triggers inflammation to a preexisting infection or antigen that causes paradoxical worsening of clinical disease. A similar phenomenon can occur in human immunodeficiency virus-negative patients, including pregnant women, neutropenic hosts, solid-organ or stem cell transplant recipients, and patients receiving tumor necrosis factor inhibitors. OBSERVATIONS We report a case of leprosy unmasking and downgrading reaction after stem cell transplantation that highlights some of the challenges inherent to the diagnosis of IRIS, especially in patients without human immunodeficiency virus infection, as well as review the spectrum of previously reported cases of IRIS reactions in this population. CONCLUSIONS The mechanism of immune reconstitution reactions is complex and variable, depending on the underlying antigen and the mechanism of immunosuppression or shift in immune status. Use of the term IRIS can aid our recognition of an important phenomenon that occurs in the setting of immunosuppression or shifts in immunity but should not deter us from thinking critically about the distinct processes that underlie this heterogeneous group of conditions.

A prospective ascertainment of cancer incidence in sub-Saharan Africa: The case of Kaposi sarcoma.

In resource‐limited areas, such as sub‐Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at‐risk population make it difficult to estimate cancer incidence. We took advantage of a large well‐enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV‐infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV‐infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person‐years, the age‐standardized incidence rate was 334/100,000 person‐years (95% CI: 314–354/100,000 person‐years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count >350 cells/mm3 was 32/100,000 person‐years (95% CI: 14–70/100,000 person‐years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV‐infected adults in East Africa equals or exceeds the most common cancers in resource‐replete settings. In resource‐limited settings, strategic efforts to improve cancer diagnosis in combination with already well‐enumerated at‐risk denominators can make healthcare systems attractive platforms for estimating cancer incidence.

Task Shifting and Skin Punch for the Histologic Diagnosis of Kaposi's Sarcoma in Sub-Saharan Africa: A Public Health Solution to a Public Health Problem

Fueled by HIV, sub-Saharan Africa has the highest incidence of Kaposis sarcoma (KS) in the world. Despite this, KS diagnosis in the region is based mostly on clinical grounds. Where biopsy is available, it has traditionally been excisional and performed by surgeons, resulting in multiple appointments, follow-up visits for suture removal, and substantial costs. We hypothesized that a simpler approach - skin punch biopsy - would make histologic diagnosis more accessible. To address this, we provided training and equipment for skin punch biopsy of suspected KS to three HIV clinics in East Africa. The procedure consisted of local anesthesia followed by a disposable cylindrical punch blade to obtain specimens. Hemostasis is facilitated by Gelfoam®. Patients removed the dressing after 4 days. From 2007 to 2013, 2,799 biopsies were performed. Although originally targeted to be used by physicians, biopsies were performed predominantly by nurses (62%), followed by physicians (15%), clinical officers (12%) and technicians (11%). There were no reports of recurrent bleeding or infection. After minimal training and provision of inexpensive equipment (USD 3.06 per biopsy), HIV clinics in East Africa can integrate same-day skin punch biopsy for suspected KS. Task shifting from physician to non-physician greatly increases access. Skin punch biopsy should be part of any HIV clinics essential procedures. This example of task shifting may also be applicable to the diagnosis of other cancers (e.g., breast) in resource-limited settings.

Bacillary Angiomatosis Masquerading as Kaposi’s Sarcoma in East Africa

Background: Bacillary angiomatosis (BA) is a rare manifestation of infection caused by Bartonella species, which leads to vasoproliferative lesions of skin and other organs. Bacillary angiomatosis affects individuals with advanced HIV disease or other immunocompromised individuals. In sub-Saharan Africa, despite the high prevalence of HIV infection and documentation of the causative Bartonella species in humans, mammalian hosts, and arthropod vectors, BA has only rarely been described. Methods: Three adult patients from Uganda and Kenya with deep purple dome-shaped papules or nodules of the skin underwent punch biopsies for histopathologic diagnosis. The biopsies of all 3 patients were sent to a local pathologist as well as to a dermatopathologist at the University of California, San Francisco. Results: All 3 patients were clinically suspected to have Kaposi’s sarcoma (KS), and local pathologists had interpreted the lesions as KS in 2 of the cases and nonspecific inflammation in the third. Histologic examination by dermatopathologists in the United States revealed nodular dermal proliferations of irregular capillaries lined by spindled to epithelioid endothelial cells. The surrounding stroma contained a mixed inflammatory infiltrate with lymphocytes, eosinophils, and neutrophils. Extracellular deposits of pale amphophilic granular material were noted in the surrounding stroma. A Warthin-Starry stain highlighted clumps of bacilli, confirming the diagnosis of BA. Conclusions: These 3 cases, to our knowledge, are the first reports of BA in East Africa in the biomedical literature. Each had been originally incorrectly diagnosed as KS. We speculate BA is underdiagnosed and underreported in resource-poor regions, such as sub-Saharan Africa, that have high endemic rates of HIV infection.

Factors associated with pruritic papular eruption of human immunodeficiency virus infection in the antiretroviral therapy era

Pruritic papular eruption (PPE) of HIV is common in HIV‐infected populations living in the tropics. Its aetiology has been attributed to insect bite reactions and it is reported to improve with antiretroviral therapy (ART). Its presence after at least 6 months of ART has been proposed as one of several markers of treatment failure.

Psoriasis as a manifestation of HIV-related immune reconstitution inflammatory syndrome

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Diagnosing Kaposi’s Sarcoma (KS) in East Africa: how accurate are clinicians and pathologists?

Author(s): Amerson, Erin; Buziba, Nathan; Wabinga, Henry; Wenger, Megan; Bwana, Mwebesa; Muyindike, Winnie; Kyakwera, Catherine; Laker, Miriam; Mbidde, Edward; Yiannoutsos, Constantin; Wools-Kaloustian, Kara; Musick, Beverly; LeBoit, Philip; McCalmont, Tim; Ruben, Beth; Volberding, Paul; Maurer, Toby; Martin, Jeffrey

Rethinking screening for thyroid autoimmunity in vitiligo

AITD: autoimmune thyroid disease TPOAb: antithyroid peroxidase antibody TSH: thyroid-stimulating hormone T he association of vitiligo with autoimmune thyroid disease (AITD) is taught as a basic tenet in dermatology. Indeed, a recent metaanalysis estimated the prevalence of thyroid dysfunction and thyroid autoantibodies in patients with vitiligo at 15.1% and 20.8%, respectively, with corresponding relative risk of 1.9 and 5.2.1z In addition, a genetic co-localization between vitiligo and thyroid autoantibodies has been established. Vitiligo may precede the onset of AITD by years. As such, screening patients with vitiligo for thyroid disease and thyroid autoantibodies is common practice among dermatologists, presumably in an effort to detect undiagnosed thyroid disease, assess risk of future thyroid disease, or both. However, recommendations in dermatology textbooks and published guidelines vary widely regarding whom to screen, when to screen, and what tests to use (Table I). Given these inconsistent recommendations, we sought to explore the rationale and evidence behind screening asymptomatic patients with vitiligo for thyroid autoimmunity, thyroid dysfunction, or both.