Bacillary Angiomatosis and Bacillary Splenitis in Immunocompetent Adults

Bacillary angiomatosis and parenchymal bacillary peliosis are recently described vascular disorders associated with infection by Rochalimaea henselae and Rochalimaea quintana, which occur in patients with either human immunodeficiency virus (HIV) infection or drug-induced immune suppression [1-5]. In addition, R. henselae and R. quintana (also the agent of trench fever) are both members of the family Rickettsiaceae [1, 4, 5], and infections due to Rochalimaea species have been associated with exposure both to cats [2] and to arthropod vectors [1, 5]. We describe five patients with cutaneous bacillary angiomatosis or bacillary splenitis without evidence of HIV infection who were determined to be immunocompetent after immunologic evaluation. In three patients with both cat and cat flea exposures, infection by R. henselae was confirmed by amplification and sequencing of 16S rDNA from an infected tissue specimen. Methods Four patients with characteristic vascular lesions of cutaneous bacillary angiomatosis [1, 3] were examined. Patient 2, who lacked vascular lesions, had a 2-week history of left-sided abdominal pain, shortness of breath, low-grade fever, nausea, diarrhea, and weight loss of 3.5 kg. Results of laboratory studies included hematocrit, 0.21 (2 months before it had been 0.34); lactate dehydrogenase, 1170 U/L; total bilirubin, 53 mol/L (3.1 mg/dL); conjugated bilirubin, 24 mol/L (1.4 mg/dL); and mildly elevated hepatic transaminases and alkaline phosphatase. A computed axial tomography scan of the abdomen showed a normal liver and hypersplenism with a 4-cm2 area of focal low attenuation. The patient underwent emergency splenectomy for impending rupture. The 1100-g spleen revealed a 4.5-cm3 mottled area consistent with infarction and two 0.6-cm3 tan nodules beneath the capsular surface. Results of routine bacterial cultures were negative. In June 1991, all five patients had blood drawn for HIV culture, serologic analysis, and polymerase chain reaction studies using techniques described previously [6, 7]. In August 1991, all patients had blood drawn for immunologic evaluation, including quantitative immunoglobulins, complement, lymphocyte subset percentages, neutrophil oxidative burst [8, 9], T-lymphocyte activation studies to phytohemagglutinin, and B-lymphocyte activation studies to pokeweed mitogen [10, 11]. After their blood was drawn, patients had skin test antigens to purified protein derivative, mumps, Trichophyton, and Candida albicans placed and read at 48 hours. The diagnosis of cutaneous bacillary angiomatosis was established using defined histopathologic criteria [3]. Bacterial DNA present in the infected tissue specimen was extracted from either frozen skin biopsy tissue (Patient 4) or from sections of formalin-fixed, paraffin-embedded biopsy specimens [1, 12]. Insufficient tissue was available from Patients 1 and 3. Extracted DNA was amplified by polymerase chain reaction using primers p24E and p12B [1, 12]. Control tissues were simultaneously extracted and amplified [1]. Amplified 16S rDNA products from Patients 2, 4, and 5 were sequenced as described previously [1]. Results Only Patient 2 had a well-documented antecedent chronic illnesshereditary spherocytosis and noninsulin-dependent diabetes mellitusand no patient was receiving immunosuppressive drugs (Table 1). Idiopathic hemochromatosis was diagnosed concomitantly with bacillary angiomatosis in Patient 3. All patients responded to oral antimicrobial therapy of 4 to 6 weeks duration. Histologic examination of skin biopsy specimens from Patients 1, 3, 4, and 5 were diagnostic of bacillary angiomatosis; splenic tissue from Patient 2 showed necrotizing splenitis with fibromyxoid changes, degenerating neutrophils, and mononuclear cells in the absence of both vascular proliferation and granuloma formation. Specimens from all patients showed many bacilli on both Warthin-Starry staining and electron microscopic examination. Table 1. Characteristics of Immunocompetent Patients with Bacillary Angiomatosis and Bacillary Splenitis Amplification of the DNA extracted from infected tissue from Patients 2, 4, and 5 produced a 16S rDNA fragment of approximately 300 base pairs. The amplified DNA fragment from tissue of Patients 2 and 4 is shown in Figure 1. The sequence of this 16S rDNA fragment from Patients 2, 4, and 5 was identical to that of R. henselae [4, 12]. Figure 1. Amplification of Rochalimaea DNA. Rochalimaea henselae R. henselae Discussion We evaluated four patients with cutaneous bacillary angiomatosis and one with bacillary splenitis and found no evidence of HIV infection using a combination of sensitive HIV antibody and antigen assays, as well as viral culture and polymerase chain reaction techniques. In addition, both cellular and humoral immunity were evaluated and no abnormality was found. Because host defense mechanisms against Rochalimaea species are not well understood, defects may have been undetected by our methods. Two patients had underlying illnesses that may be associated with altered immune function, but no consistent immune defect has been associated with these conditions [13-15]. The histopathologic findings were diagnostic for bacillary angiomatosis in all four patients with cutaneous disease; tissue from Patient 2 showed necrotizing splenitis with characteristic bacillary organisms [3, 12]. Amplification and sequencing of rDNA from tissue of Patients 2, 4, and 5 confirmed that the infecting organism was R. henselae. Although we cannot speciate the bacilli seen in abundance with the Warthin-Starry stains of Patients 1 and 3, the histopathologic changes met all criteria for the diagnosis of cutaneous bacillary angiomatosis [3], a disease associated with R. henselae and R. quintana [1]. Bacillary splenitis in the absence of peliosis appears to be another manifestation of R. henselae infection. A clinical spectrum of R. henselae infection may exist, beginning with fever and bacteremia, progressing to bacillary splenitis and finally to bacillary peliosis. Differences in host immune function also may play a role in disease progression. The diagnosis of cutaneous bacillary angiomatosis and bacillary splenitis should be pursued in the immunocompetent patient when clinical or histopathologic features are suggestive. On the basis of these five patients, we recommend treatment with erythromycin or doxycycline for at least 6 weeks when the diagnosis is confirmed.