Journal of the Louisiana State Medical Society
Histopathologic assessment is needed for diagnostic confirmation of KS. The typical stages include the macular, patch, and nodular stages, each with different degrees of angiogenesis, inflammation, and proliferation. 37 Immunohis- tochemical staining using monoclonal antibodies targeting the HHV-8 latent nuclear antigen-1 (LNA-1) is considered the gold standard for diagnosis of KS, as it has a very high sensitivity and specificity. 38 Staining with D2-40, CD31, and CD34 are used as adjunct stains, although the specificity for these markers is lower. STAGING AND TREATMENT AIDS-related KS patients are stratified into risk catego- ries based on three parameters: Extent of tumor (T), Immune status (I), and Severity of systemic illness (S). Patients are given a zero or one in each category. This staging system was developed by the AIDS Clinical Trial Group (ACTG) of the National Institute of Health in 1989 and revised in 1997. 39,40 This staging should only be used for AIDS-related KS, and there is currently no universally accepted staging system for the other subtypes. cART is recommended for all patients with AIDS-relat- ed KS. In the mid-1990s, the incidence and overall survival with KS dramatically changed with the introduction of cART. A French cohort study of HIV patients showed that the incidence fell from 32 per 1,000 person-years in 1993 to 3 per 1,000 person-years in 1999. 41 A similar study in 2011 showed that the cumulative incidence of Kaposi sarcoma was 14.3% from 1980 to 1989, 6.7% from 1990 to 1995, and 1.8% from 1996 to 2006. 7 Similarly, patients with KS showed significantly higher survival rates in the cART era as com- pared to the pre-cART era. 42 The improvement in prognosis may in part be explained by overall immune reconstitution, rather than regression of tumor. A small number of patients (6%-14%) may develop worsening of their disease after the initiation of cART, which is thought to be due to the IRIS. 43,44 Most patients who develop IRIS-induced KS flares are able to tolerate continuation of cART. 43 Systemic chemotherapy is usually reserved for patients with more extensive or rapidly progressive disease. The 2008 British HIV Association guidelines for HIV-associated malignancies recommend that the decision to use systemic chemotherapy should be based on a number of parameters, including prognostic index, initial response to cART, patient performance status, and end organ function. 45 Furthermore, disseminated tumors (widespread skin involvement, exten- sive oral involvement, tumor-associated edema or ulcer- ation, visceral involvement) and those with IRIS-induced KS flares should be considered for chemotherapy. 45 Liposomal anthracyclines (doxorubicin, daunorubicin) and taxanes (pa- clitaxel) are the mainstays of treatment. 45 Despite the use of cART and standard chemotherapy, Stage III disease (T 1 I 1 S 1 ) portends a particularly poor prognosis, with a median sur- vival of only 15 months. 40 Ganciclovir has demonstrated activity against HHV-8 andmay be useful in the prevention
of KS in high-risk patients. 46 Local therapywith intralesional vinblastine, radiation, and other topical agents is typically used for cosmesis or reduction in symptoms associatedwith bulky lesions but does not prevent progression of disease in other tissues. PAECILOMYCES Paecilomyces is a filamentous fungus common in the environment, inhabiting the soil, decaying plants, and food products. Although often viewed as a contaminant, it has been known to cause a variety of diseases in humans and animals, including pneumonia in immunocompromised hosts. While there are only a handful of case reports, the most commonly reported species linked to respiratory infections are P. variotii and P. lilacinus . Respiratory tract infection with P. lilacinus is usually characterized by pleural effusions and pulmonary abscess, while P. variotii can pres- ent with hilar lymphadenopathy, cavitary lesions, confluent patchy opacities, and pulmonary nodules. It is important to differentiate species as they display different resistance patterns to antifungal therapy, with reports of poor suscep- tibility to amphotericin B, itraconazole, and echinocandins for P. variotii . 47 It is unclear if Paecilomyces played a role in our patient’s disease process. However, his clinical and radiographic improvement with antifungal therapy leads us to believe his respiratory symptoms were at least partly due to fungal pneumonia. CONCLUSION KSwas one of themost feared complications in the early AIDS epidemic. A once rare disease exploded onto the scene in the early 1980s and was quite morbid and potentially fatal to those afflicted. Advances in cART in the mid-1990s have been essential to reducing the prevalence, morbidity, andmortality associated with this disease. The discovery of HHV-8 as the cause for KS in 1994was critical to understand- ing its pathophysiology. Although the exact mechanism of transmission has yet to be proven, studies suggest sexual transmission, possibly by exposure to saliva, as the most likely vector. Inflammation and immunosuppression in the setting of HHV-8 infection have been shown to cause KS proliferation leading to tumor formation. Corticosteroids can induce KS tumorigenesis and exacerbate pre-existing le- sions, often leading to disseminated disease. Consequently, steroids should be avoided if there is reasonable suspicion for the presence of KS. Clinical presentations range from focal skin involvement to extensive involvement of visceral organs. More fulminant presentations are more common in HIV-infected patients, particularly those who are not on cART. While a clinical diagnosis can be made by observing classic lesions, definitive diagnosis is made by histology and immunohistochemical staining to identifyHHV-8 latent nuclear antigen-1. Staging is based on the extent of tumor burden, immune status, performance status, and coexisting
228 J La State Med Soc VOL 166 September/October 2014
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