Hemophagocytic Lymphohistiocytosis: An Unusual Initial Presentation of Acute HIV Infection

Abstract

To the Editor: Hemophagocytic lymphohistiocytosis (HLH) has been described in HIV-infected patients who developed opportunistic infections or malignancies.1,2 The hypercytokinemia triggered by malignancy or coinfection with human herpesvirus-8 or other opportunistic infections and the generalized defects in T-cell and natural killer (NK) cell cytotoxicity in HIV-infected patients are characteristic immunologic features of HLH,3,4 which explains the predisposition to HLH in patients with HIV infection. HLH could also be one of the manifestations of acute HIV infection,5-8 although it has rarely been described to date.9 Here, we present 3 cases of HLH as the initial presentation of acute HIV infection and review the literature.5-8 Detailed clinical characteristics of the 7 cases of HLH of patients with acute HIV infection, including our 3 cases, are shown in Table 1.Table 1: Clinical Characteristics of 7 Patients With Acute HIV Infection and HLHOf the 7 patients diagnosed with acute HIV infection and HLH, 4 were homosexual men. Their median age was 27 years (range: 18-31 years). The presenting symptoms of acute HIV infection were fever (100%), generalized or localized lymphadenopathy (100%), sore throat (86%), and skin rashes (71%). Hepatomegaly or splenomegaly (100%) was detected by physical examination or image studies (see Table 1). Five patients had oroesophageal candidiasis. Severe complications were found in 3 patients: 2 patients developed encephalopathy;6,7 1 had renal failure, acute pancreatitis, and pancreatic panniculitis;7 and 1 had blurred vision.8 Laboratory data showed leukopenia (median value = 2200 cells/μL, range: 1400-10,085 cells/μL), anemia (median value = 12.2 g/dL, range: 9-15.7 g/dL), thrombocytopenia (median value = 175,000 cells/μL, range: 99,000-184,000 cells/μL), hyperferritinemia (median value = 10,817.5 ng/dL, range: 2227-29,893 ng/dL), and elevated lactate dehydrogenase (LDH) levels (median = 1483 U/L, range: 989-4769 U/L). The CD4 lymphocyte counts of the 7 patients were low at the time acute HIV infection was diagnosed, with a median count of 247 cells/μL (range: 63-500 cells/μL), and the median CD8 count was 1302 cells/μL (range: 364-1617 cells/μL). Plasma HIV RNA load was available in 4 patients, with a median value of 5.88 log10 copies/mL by reverse transcriptase-polymerase chain reaction (RT-PCR; range: 5.72-5.88 log10 copies/mL). Histiocytosis with hemophagocytosis was demonstrated in biopsies of the bone marrow or lymph nodes. Acute HIV infection has long been a difficult diagnosis to make because of its nonspecific symptoms.9 Compared with the patients previously described and reviewed, who had opportunistic infections or malignancies at the diagnosis of HLH,1,2 all 7 patients with acute HIV infection and HLH had fever, generalized or localized lymphadenopathy, and hepatomegaly or splenomegaly at presentation. Less hypertriglyceridemia and higher CD4 counts were noted. All patients survived after supportive care was instituted. Although some of them had received immunomodulating agents, such as intravenous immunoglobulin (3 patients) and steroids (2 patients), the benefit of these agents in the treatment of HLH associated with acute HIV infection remains unclear. Our experience and our review of the literature suggest that hemophagocytosis could be one of the initial presentations of acute HIV infection. Hsin-Yun Sun Mao-Yuan Chen Chi-Tai Fang Szu-Min Hsieh Chien-Ching Hung Shan-Chwen Chang *Department of Internal Medicine,, National Taiwan University Hospital and National Taiwan University College of Medicine,, Tapei, Taiwan; and, †Department of Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan