Ebrahim, S

Moodley, J

Ramdial, PK

Singh, B

LSHTM Research Online

Ebrahim, S; Singh, B; Moodley, J; Ramdial, P K (2009) Kaposi’ssarcoma, lymphoedema and gangrene in AIDS–a therapeutic chal-lenge. South African journal of surgery. Suid-Afrikaanse tydskrif virchirurgie, 47 (2). pp. 62-3. ISSN 0038-2361Downloaded from: http://researchonline.lshtm.ac.uk/20076/DOI:Usage GuidelinesPlease refer to usage guidelines at http://researchonline.lshtm.ac.uk/policies.html or alterna-tively contact researchonline@lshtm.ac.uk.Available under license: Creative Commons Attribution Non-commercialhttp://creativecommons.org/licenses/by-nc/3.0/TraumaSAJS62   The manifestations of the HIV pandemic are manifold, affecting all organ systems. With respect to the vascular sys-tem, it is recognised that vasculitides constitute one of the less common but none the less challenging consequences of HIV infection.1 The HIV pandemic has also seen a dramatic increase in the prevalence of Kaposi’s sarcoma2 and its fre-quently associated complication of chronic lymphoedema.3 When these three manifestations of HIV (Kaposi’s sarcoma, lymphoedema and vasculopathy) coexist in the same limb, as in this report, unique clinical and management challenges are presented.Case report A 34-year-old man who had been confirmed HIV positive a year earlier presented to the surgical services at King Edward VIII Hospital, Durban, with a 1-month history of rest pain in the right leg with associated gangrene of the little toe. In addition to generalised lymphadenopathy, the patient was noted to have right femoro-popliteal arterial disease with dry gangrene of the right fifth toe and skin changes sugges-tive of ischaemic changes along the second, third and fourth toes. Purple nodular lesions were noted on both lower limbs, suggestive of Kaposi’s sarcoma. Non-pitting oedema up to the level of the right knee was also evident, less so on the opposite limb. The clinical assessment was critical ischaemia of the right lower limb with associated chronic lymphoedema secondary to Kaposi’s sarcoma. The haemoglobin level was 12.6 g/dl, the white cell count 8.2×109/l, and the platelet count 479×109/l. The urea and electrolyte levels and the results of liver function tests were normal. The international normalised ratio (INR) measured 1.08 and the CD4 count was 110 cells/µl.The thrombophilia screen (antithrombin III, protein C, protein S levels) was normal. A skin biopsy of the nodular lesions confirmed Kaposi’s sarcoma. The chest radiograph was normal. A venous Doppler study excluded a deep-vein thrombosis. The right common and superficial femoral arteries appeared normal on arterial duplex Doppler examination. However, extensive ‘beading’ was noted in the right popliteal artery, which appeared patent at the knee. A thrombus was noted in the distal popliteal artery with a ‘knocking’ pulse. No flow was detected in the distal popliteal or tibial arteries at the ankle. A computed tomography angiogram of the lower limbs revealed a sharp cut-off of vessels below the right knee, sug-gestive of thrombus formation. Poor distal flow was noted, and the rest of the vessels were normal. The patient was commenced on highly active antiretroviral therapy (HAART) and anticoagulation. A distal limb abla-tion was undertaken after demarcation of the gangrenous segments. The patient is currently receiving oncotherapy for management of the Kaposi’s sarcoma. Discussion Understanding the pathogenesis and formulating the effective management of HIV-associated vasculopathy and Kaposi’s sarcoma-associated lymphoedema remains a challenge to the attendant practitioner. When these manifestations of HIV occur together (and on the same limb) this challenge is increased, since the treatment of one may compromise the treatment of the other.Kaposi’s sarcoma is caused by Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8). In the early 1980s the increasingly frequent diagno-sis of Kaposi’s sarcoma in AIDS patients led to the inference that AIDS weakened the immune system.4The incidence of Kaposi’s sarcoma has declined sharply since HAART became widely available, and HAART is indispensable in the treatment of epidemic Kaposi’s sarcoma. In 40% or more of patients with AIDS-related Kaposi’s sarcoma, the lesions will regress upon commencement of HAART.5,6 In some patients, however, Kaposi’s sarcoma may recur after years of HAART, especially if HIV is not com-Kaposi’s sarcoma, lymphoedema and gangrene in AIDS – a therapeutic challengeS. EBRAHIM, M.B. CH.B. B. SINGH, F.C.S. (S.A.), M.D. J. MOODLEY, F.C.S. (S.A.), M.MED.SCI. Department of General Surgery, Nelson R. Mandela School of Medicine, Faculty of Health Sciences, University of KwaZulu-Natal, DurbanP. K. RAMDIAL, F.C.PATH. (S.A.), M.MED.Department of Pathology, Nelson R. Mandela School of MedicineCase ReportVOL 47, NO. 2, MAY 2009   SAJSKaposi.indd   62 5/25/09   3:57:03 PMSAJSARTICLES 63pletely suppressed. Patients with a few local lesions can often be treated with local measures such as radiation therapy or cryotherapy. Surgery is generally not recommended, as Kaposi’s sarcoma can appear in wound edges. More wide-spread disease, or disease affecting internal organs, is gener-ally treated with systemic therapy with interferon alpha and liposomal anthracyclines.7Obstructive lymphoedema caused by AIDS-related Kaposi’s sarcoma, although previously rare, is now being seen with increasing frequency.2 It is suggested that lymphatic and venous obstruction, protein-rich interstitial fluid, tissue haemosiderin and subcutaneous infection contribute to the evolution and perpetuation of chronic lymphoedema.3 Morbidity and mortality in patients with Kaposi’s sarcoma-associated lymphoedema is influenced by coexistent sepsis because of stasis and trauma; the recognition of infection may therefore be limb- or life-saving.2Many types of vasculitis have been reported in HIV-posi-tive patients, affecting mainly small and medium-sized ves-sels. Large vessels can also be involved, usually as part of a leucocytoclastic vasculitis of the vasa vasora or periadventitial vessels.1 Large-vessel vasculopathy consists of either aneu-rysms or occlusive disease. Arteries affected include the com-mon carotid, abdominal aorta, common iliac, femoral and popliteal.7Primary arterial thrombosis associated with HIV infection, as in the case reported here, is a distinct clinicopathologi-cal entity. Young patients particularly are at increased risk. Involvement of both upper and lower limbs is documented, presenting with varying degrees of ischaemia ranging from claudication to frank tissue necrosis.8Vascular occlusion is on the basis of an organising localised thrombus within the vessel lumen, with no evidence of ath-erosclerosis in the intima. The major changes involve the adventitia and the peri-adventitial area, with leucoclastic vasculitis of the vasa vasora.8 Significant features include the normality of the arterial tree proximal to the thrombosed arteries, and thrombosis of the distal vessels with no demon-strable run-off. Typically, Duplex ultrasonography shows hyperechoic ‘spotting’ in the arterial wall with the ‘string of pearls’ sign, found to be a sensitive indicator of HIV throm-bosis.9While several causes of primary HIV-associated thrombo-sis have been documented, its pathophysiology is not well understood. In general, HIV infection is associated with aberrations of coagulation that include thrombocytopenia and hypercoagulable states. Hypercoagulable states are pre-disposed to by acquired protein C and protein S deficiency, as well as by elevated levels of antiphospholipid antibodies and von Willebrand factor. Thrombectomy usually results in thrombus recurrence within 48 hours, and whether it impacts on level of ablation is not known at present. The anecdotal use of steroids after thrombectomy has not been found to prevent re-thrombosis. Vascular grafts have been used with satisfactory outcome being reported.9 However, this option may be contraindi-cated in patients with associated Kaposi’s sarcoma. The occurrence together of Kaposi’s sarcoma (with or without associated lymphoedema) and vascular manifesta-tions of HIV may be considered an uncommon presentation in the HIV patient; however, the sheer scale of the pandemic will see an increase of this problem that will prompt innova-tive clinical decisions to facilitate appropriate therapy. REFERENCES1.  Chetty R. Vasculitides associated with HIV infection. J Clin Pathol 2001; 54: 275-278.2.  Allen PJ, Gillespie DL, Redfield RR, Gomez ER. Lower extremity lymph-edema caused by acquired immune deficiency syndrome related Kaposi’s sarcoma: Case report and review of the literature. J Vasc Surg 1995; 22: 178-181.3.  Ramdial PK, Singh B, Singh R, Aboobaker J. Lymphedematous HIV-associ-ated Kaposi’s sarcoma. J Cutan Pathol 2006; 33: 474-481.4.  Antman K, Chang Y. Kaposi’s sarcoma. N Engl J Med 2000; 342(14): 1027-1038.5.  Hernandez-Morales DE, Hernandez-Zaccaro AE. Gastrointestinal and cutaneous AIDS-related Kaposi’s sarcoma: different activity of liposomal doxorubicin according to location of lesions. Eur J Cancer Care  2005; 14(3): 264-266.6.  Yarchoan R, Tosatu G, Little RF. Therapy insight: AIDS-related malignancy – the influence of antiviral therapy on pathogenesis and management. Na-ture Clinical Practice Oncology 2005; 2(8): 406-415.7.  Chetty R, Batitang S, Nair R. Large artery vasculopathy in HIV-positive patients:   another vasculitic enigma. Hum Pathol 2000; 31: 374-379.8.  Mulaudzi TV, Pillay B, Moodley J, Magagula T, Thusini ZC. Thrombec-tomy in HIV Related peripheral arterial thrombosis: a preliminary report. Eur J Vasc Endovasc Surg 2005; 30: 102-106.9.  Woolgar JD, Ray R, Maharaj K, Robbs JV. Colour Doppler and grey scale ultrasound features of HIV-related vascular aneurysms. Br J Radiol 2002; 75: 884-888.SAJS   VOL 47, NO. 2, MAY 2009Kaposi.indd   63 5/25/09   3:57:04 PM

Kaposi's sarcoma, lymphoedema and gangrene in AIDS--a therapeutic challenge.

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Kaposi's sarcoma, lymphoedema and gangrene in AIDS--a therapeutic challenge.

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