Original Article
Isolation of Rochalimaea Species from Cutaneous and Osseous Lesions of Bacillary Angiomatosis
N Engl J Med 1992; 327:1625-1631December 3, 1992
- Abstract
- Abstract
Background.
Bacillary angiomatosis is characterized by vascular lesions, which occur usually in patients infected with the human immunodeficiency virus (HIV). A newly described gram-negative organism, Rochalimaea henselae, has been associated with cutaneous bacillary angiomatosis, but no organism has been isolated and cultivated directly from cutaneous tissue.
Methods.
We used two methods to isolate the infecting bacterium from four HIV-infected patients with cutaneous lesions suggestive of bacillary angiomatosis: cultivation with eukaryotic tissue-culture monolayers and direct plating of homogenized tissue onto agar. The patients' blood was cultured with the lysis—centrifugation method. Isolates recovered from skin and blood were identified by sequencing all or part of the 16S ribosomal RNA gene amplified with the polymerase chain reaction.
Results.
R. quintana, historically known as the agent of trench fever, was isolated from cutaneous lesions in three patients, after tissue homogenates were cultivated with endothelial-cell monolayers; R. henselae was isolated from a cutaneous lesion in one patient. In two patients, R. quintana was isolated from both cutaneous tissue and blood; in one patient it was also isolated from bone.
Conclusions.
In bacillary angiomatosis, either of two species of rochalimaea — R. quintana or R. henselae —can be isolated from cutaneous lesions or blood, providing an additional method of diagnosis. (N Engl J Med 1992; 327:1625–31.)
Media in This Article
Figure 1
Cutaneous Lesions of Bacillary Angiomatosis on the Right Thigh of Patient 1.Figure 2
Cutaneous and Osseous Lesions on the Left Leg of Patient 2 at the Time of the Diagnosis of Bacillary Angiomatosis.Article Activity
- Article
BACILLARY angiomatosis is a newly recognized infectious disease, primarily affecting immunocompromised patients, most commonly those infected with the human immunodeficiency virus (HIV). The most common cutaneous lesions are angiomatous, tender papules or subcutaneous nodules, which occasionally resemble Kaposi's sarcoma.1 2 3 4 In 1990, the agent of bacillary angiomatosis was identified as being closely related to Rochalimaea quintana on the basis of partial sequencing of the 16S ribosomal RNA gene (16S ribosomal DNA [rDNA]) extracted from infected tissue.5 Recently, comparison of the 16S ribosomal RNA sequences of a proposed etiologic agent of cat scratch disease, Afipia felis, 6 7 8 9 with those of Bartonella bacilliformis, 8 R. quintana, 10 and the agent of bacillary angiomatosis described by Relman et al.5 revealed that this agent represents a new rochalimaea species, designated R. henselae. 11 , 12 The spectrum of disease caused by R. henselae includes bacteremia in the absence of cutaneous lesions in immunocompromised and immunocompetent patients,13 , 14 bacillary peliosis hepatis,15 and splenitis (Tappero JW: unpublished data).
Cultivation of the causative organism from cutaneous lesions of bacillary angiomatosis and propagation on solid agar have been unsuccessful previously. We attempted to isolate and propagate rochalimaea species from cutaneous and osseous lesions of bacillary angiomatosis in four HIV-infected patients.
Case Reports
Patient 1
Patient 1, a 44-year-old homosexual man with the acquired immunodeficiency syndrome (AIDS), presented with a painful, deep swelling of the right side of the groin eight months before bacillary angiomatosis was diagnosed. Magnetic resonance imaging of the right thigh showed a lobulated soft-tissue mass (Fig. 1Figure 1
Cutaneous Lesions of Bacillary Angiomatosis on the Right Thigh of Patient 1.A). Doppler ultrasonography demonstrated a pattern of markedly increased vascular flow. An incisional biopsy was performed and revealed a complex, thick-walled, cavitary abscess that was not purulent. The pathological diagnosis was abscess and granulation tissue with fat necrosis, and routine cultures and stains were negative.Six weeks before being given a diagnosis of bacillary angiomatosis, the patient presented with an indurated erythematous plaque overlying the site of the previous biopsy. His CD4+ count was 7 per cubic millimeter (0.007×109 per liter). Two weeks before the diagnosis, he presented with low-grade fever and night sweats and had numerous painful angiomatous nodules throughout an erythematous plaque measuring 10 by 15 cm on the anterior right thigh (Fig. 1B). Histologic examination of a biopsy specimen showed changes characteristic of bacillary angiomatosis. Steiner silver staining revealed bacilli, and a small gram-negative rod later identified as R. quintana was cultured with the use of special techniques (described below). Treatment with erythromycin in a dose of 500 mg four times a day was started and was subsequently changed to doxycycline five days later because of gastrointestinal intolerance. The lesion on the right thigh gradually healed during six weeks of treatment with 100 mg of doxycycline twice a day. The patient reported no history of exposure to animals or arthropods.
Patient 2
Patient 2 was a 51-year-old homosexual man who presented with Pneumocystis carinii pneumonia six months before bacillary angiomatosis was diagnosed. Four weeks before the diagnosis, he presented with fever and diffuse muscle tenderness. His CD4+ count was 126 per cubic millimeter (0.126×109 per liter), and the creatine kinase concentration was normal. Three weeks before the diagnosis, he had pain and swelling in the left leg. On examination, the patient had a temperature of 38°C and an 8-cm erythematous, nodular plaque on the left leg surrounded by distended veins (Fig. 2Figure 2
Cutaneous and Osseous Lesions on the Left Leg of Patient 2 at the Time of the Diagnosis of Bacillary Angiomatosis.A). A roentgenogram revealed a lytic lesion along the anterior aspect of the left distal tibia (Fig. 2B), and bone-scan findings were consistent with acute osteomyelitis.Biopsy of a deep, subcutaneous nodule was not diagnostic; therefore, an open excisional biopsy of the tibial lesion was performed. Routine histologic analysis showed chronic inflammation with granulation tissue, sparse vascular proliferation, and new bone formation; Steiner staining did not show bacilli. DNA extracted from bone and amplified by the polymerase chain reaction (PCR)16 produced a 16S rDNA fragment of the expected size for rochalimaea species, and a presumptive diagnosis of bacillary angiomatosis was made. Characteristic organisms were subsequently identified on electron microscopy, and R. quintana was isolated from both the bone and surrounding soft tissue. Therapy with erythromycin at a dose of 500 mg four times a day was begun. The cutaneous and osseous lesions gradually resolved over the following four months of treatment.
Four weeks after the cessation of erythromycin therapy, the patient began to have left-arm pain, fever, and night sweats. On examination, he had multiple tender venous thromboses with overlying erythema. The veins affected were distributed over the entire arm and did not involve a specific region of drainage. There was no history or evidence of intravenous drug use, trauma to the arm, or axillary lymphadenopathy. Blood samples were drawn into lysis—centrifugation tubes for culture, and the cultures grew R. quintana. Treatment with erythromycin was resumed, with resolution of the arm thromboses and systemic symptoms. The patient denied exposure to arthropods or cats, although he had a pet rat.
Patient 3
Patient 3 was a 41-year-old homosexual man with a history of intravenous drug use in whom P. carinii pneumonia was diagnosed seven months before bacillary angiomatosis was diagnosed. His CD4+ count was 20 per cubic millimeter (0.020×109 per liter). Two skin lesions measuring 1.5 by 1.5 cm developed on both legs four months before the diagnosis. Both lesions had the macroscopic appearance of bacillary angiomatosis, but the results of two biopsies were not diagnostic histopathologically because of a paucity of angiomatous changes. A third biopsy of the left-leg lesion was performed. Routine histologic staining revealed acute inflammation, necrosis, and granulation tissue. Warthin—Starry staining was negative for organisms, but the patient had received three doses of erythromycin four days before the biopsy.
During the two months before bacillary angiomatosis was diagnosed, intermittent fevers developed, the left-leg lesion continued to grow, and left inguinal (node measuring 1.5 by 3 cm) and left supraclavicular (node measuring 4 by 4 cm) adenopathy developed that was painful. The lesion on the left leg is shown in Figure 3Figure 3
Cutaneous Lesion on the Left Leg of Patient 3 at the Time of the Diagnosis of Bacillary Angiomatosis.. A punch biopsy showed granulation tissue with focal areas of acute inflammation, and Warthin—Starry staining revealed clusters of bacilli. Special cultures of the biopsy tissue grew R. henselae. After the first doses of erythromycin, the patient's temperature abruptly increased to 40°C and diffuse myalgias developed. The antibiotic therapy was changed first to doxycycline and then to tetracycline because his acute symptoms were attributed to intolerance to these drugs. These symptoms abated after the first several days of therapy, and he completed two months of treatment with tetracycline at a dose of 500 mg four times a day. The left-leg lesion, as well as both enlarged lymph nodes, resolved completely. The patient had received numerous scratches from his flea-infested adult cat and new kitten.Patient 4
Patient 4 was a 34-year-old HIV-positive homosexual man who had had no AIDS-defining illness. Eight months before being given a diagnosis of bacillary angiomatosis, he presented with a diffuse, pruritic rash of three weeks' duration and three erythematous scaly plaques measuring 1 to 3 cm2. A diagnosis of scabies was made when mites were demonstrated microscopically, and he was treated with 1 percent lindane, with resolution of the rash. Several weeks later intermittent fevers developed; the three hyperkeratotic plaques on the lower extremities were unchanged. A punch biopsy revealed suppurative dermatitis with abundant leukocytoclastic debris but only slight vascular proliferation; Warthin—Starry staining was not performed. Five months before the diagnosis, the patient had another punch biopsy, which again showed a diffuse neutrophilic infiltrate, with negative staining for organisms and minimal vascular proliferation. The patient was treated for 10 days with doxycycline by his private physician, and the lesions began to drain and decrease in size. However, after treatment with doxycycline was stopped, additional lesions appeared on the legs and buttocks over the next several months, and a third biopsy performed one month before diagnosis showed acute and chronic inflammation, with a suggestion of bacillary organisms on Warthin—Starry staining. The CD4+ count was 7 per cubic millimeter (0.007×109 per liter). A subsequent skin biopsy was not diagnostic, but cultures of both tissue and blood grew R. quintana. The patient received three months of erythromycin (500 mg four times a day), with resolution of cutaneous lesions and fever. He had fevers of up to 40°C and 39.7°C after the second and third doses of erythromycin, respectively. The patient denied having any direct contact with animals or arthropods.
Methods
Bacterial Strains and Cell-Culture Lines
Type strains of R. quintana (VR 358) and B. bacilliformis (35685) were obtained from the American Type Culture Collection (ATCC, Rockville, Md.). The type strain of R. henselae (49882) was provided by Dr. Russell Regnery, Viral and Rickettsial Zoonoses Branch, Centers for Disease Control and Prevention, Atlanta; A. felis was isolated by one of us.
The following tissue-culture cell lines were inoculated: HeLa epithelioid carcinoma, L929 mouse-fibroblast, and CPA bovine endothelial monolayers. The CPA endothelial-cell line was obtained from the University of California—San Francisco (UCSF) Cell Culture Facility (ATCC cell-culture line 207). This monolayer consists of bovine pulmonary-artery endothelial cells and diners morphologically from human umbilical-vein endothelial cells.17
Inoculation and Recovery of Rochalimaea Species from Cutaneous and Osseous Lesions
Approval for this study was obtained from the UCSF Committees on Human Research and Biosafety. After informed consent was obtained, cutaneous tissue was obtained by punch biopsy from two different sites that had been cleaned with povidone—iodine. Additional specimens were submitted for routine cultures and histologic studies.
The specimens from the various biopsy sites were transported and processed separately: they were washed, minced as finely as possible, and then homogenized. Separate tissue-culture monolayers were inoculated with homogenate and grown in supplemented medium 199, containing medium 199 with Earle's balanced salt solution (UCSF Cell Culture Facility), supplemented with 20 percent fetal-calf serum, glutamine, and sodium pyruvate (GIBCO Laboratories, Grand Island, N.Y.). Three cell monolayers were inoculated with specimens from Patient 1 — HeLa, L929, and CPA — whereas only the CPA monolayer was inoculated with specimens from Patients 2, 3, and 4. The flasks were incubated at 36°C in the presence of 6 percent carbon dioxide and 85 percent humidity. At the time of monolayer inoculation, an aliquot of homogenate was also plated onto three different solid agars: chocolate agar, trypticase soy agar with 5 percent defibrinated sheep's blood, and heart-infusion agar with 5 percent whole rabbit blood13 (San Francisco General Hospital Media Facility, San Francisco). No antibiotics were added to any solid or liquid medium. Plates were incubated for three to four weeks at 36°C in sterile candle jars. Uninfected monolayers were passaged and plated onto solid agar to control for contamination. To assess the recovery of rochalimaea species in the absence of endothelial-cell monolayer, supplemented medium 199 alone was inoculated with the specimens from Patients 3 and 4.
Inoculation and Recovery of Rochalimaea Species from Blood
Blood cultures were performed for all patients by the lysis—centrifugation method13 (Wampole Laboratories, Cranbury, N.J.) and plated onto the three different agars. Solid agar and supplemented medium 199 were inoculated with the medium used for the homogenized specimen to control for the sterility of the medium, equipment, and processing.
DNA Amplification
PCR was performed with synthetic oligonucleotide primers (UCSF Biomolecular Resource Center) corresponding to p24E and p12B under conditions described by Relman et al.5 There are 241 nucleotides between these primers. In addition, for isolates from Patients 1 and 2, two additional pairs of primers were used to amplify the entire 16S rDNA, in two halves, with overlapping primers adapted from the primers POmod and PC3mod (the 5′ half) and P3mod and PC5 (the 3′ half).18 To corroborate the speciation of isolates further, the citrate synthase gene was amplified, and the product was digested with several restriction endonucleases.11 The DNA template was obtained from agar-grown single colonies of isolates and from frozen biopsy tissue. Special precautions were taken to prevent contamination with exogenous DNA during amplification.19 Each set of reactions included a negative control: a tube containing all the reagents but not the template DNA. To provide an additional negative control, the DNA template was extracted from frozen tissue from an HIV-infected patient with Kaposi's sarcoma and amplified at the same time as the tissue from the four study patients. In the case of Patient 1, the DNA template was extracted from the formalin-fixed surgical biopsy specimen embedded in paraffin and a biopsy specimen from a matched control patient, and then both were amplified with PCR.20
DNA Sequencing
The products of DNA amplification were digested with the appropriate restriction endonucleases, ligated into the vector pUC18 (Pharmacia, Piscataway, N.J.), and used to transform Escherichia coli. The sequence was obtained from the double-stranded DNA of recombinants with the Taq Dye Primer Cycle Sequencing kit and the dideoxy-sequencing method,21 followed by analysis on an automated sequencer (Applied Biosystems, Foster City, Calif.). A minimum of three different clones containing the fragment of 241 base pairs (bp) were sequenced for isolates from each patient. In addition, the entire 16S rDNA of one isolate from Patients 1 and 2 was sequenced and then compared with the corresponding sequences for rochalimaea species available in the GenBank (Los Alamos, N.M.)/ European Molecular Biology Laboratory (Heidelberg, Germany) data bases.
Results
Inoculation and Recovery of Rochalimaea Species from Cutaneous and Osseous Lesions
The characteristics of the cutaneous lesions of bacillary angiomatosis and the rochalimaea species isolated are summarized in Table 1Table 1
Characteristics of Cutaneous Lesions of Bacillary Angiomatosis and Method of Rochalimaea Isolation.. R. henselae was recovered by direct plating of homogenized tissue from the one patient infected with this organism (Patient 3). However, for two of the patients with R. quintana infection, the organism was isolated only after cocultivation with an endothelial-cell monolayer. The infected CPA monolayer was incubated for 9 to 36 days until growth of R. quintana was apparent on the basis of the increased turbidity of the supernatant. After the monolayer supernatant had been plated onto solid agar, microbial colonies became evident on the agar after additional incubation for 6 to 20 days. Once the culture method was streamlined, the length of time from the inoculation of cutaneous tissue to the recovery of organisms on solid agar was about 21 days. In general, fresh chocolate-agar plates permitted the best growth and recovery of rochalimaea species. Colonies were also isolated from heart-infusion agar with 5 percent whole rabbit blood, and less frequently from trypticase soy agar with 5 percent defibrinated sheep's blood.In the absence of the monolayer, no colonies grew after the inoculated medium was plated onto solid agar. Solid agar inoculated with the medium overlying the L929 and HeLa cell lines was also negative for growth. All conventional microbiologic cultures of skin and bone from the four patients were negative, as were plates inoculated with medium alone or with uninfected, homogenized tissue-culture monolayers. The R. quintana and R. henselae colonies initially looked strikingly different. The R. henselae colonies caused pitting of the agar during the first passages, as previously described,11 but on further passage, smooth, nonpitting colonies more phenotypically similar to those of R. quintana spontaneously arose among the rough colonies. Both the rough and smooth forms were identified as R. henselae by 16S rDNA sequencing. Gram staining of all isolates revealed thin, gram-negative rods. No culture of R. quintana was present in the laboratory until eight weeks after the isolation of R. quintana from the second patient, when it was ordered from the ATCC, ruling out the possibility of laboratory-induced contamination.
Despite the heavy growth of R. quintana in the liquid medium overlying the monolayers, the CPA cells remained attached and viable for as long as two months, even when the medium infected with the rochalimaea bacilli was not replenished. The endothelial cells also underwent a morphologic change: formerly flat and spreading, they became elongated with a more tubular appearance.
Inoculation and Recovery of Rochalimaea Species from Blood
No organisms were isolated from lysis—centrifugation tubes containing blood samples from the first three patients. The lysis—centrifugation blood cultures of the fourth patient were positive for R. quintana, with an estimated 0.7 colony-forming unit per milliliter of blood (Table 1). Blood cultures drawn during a recurrence of the bacillary angiomatosis infection in Patient 2 grew nearly confluent colonies of R. quintana, with more than 500 colony-forming units per milliliter of blood. Control plates containing medium alone were negative.
DNA Amplification
PCR amplification of the DNA extracted from the original tissue specimens from all four patients and of the DNA from colonies of rochalimaea species isolated from these patients resulted in a product of approximately 300 bp, with the use of primers p24E and p12B5 (Fig. 4Figure 4
PCR-Amplified 16S rDNA Fragments from Tissue and Bacterial DNA Extracts.A). This fragment migrated with the fragment produced with the DNA template from ATCC type strains of R. quintana, R. henselae, and B. bacilliformis. No amplification product was obtained from A. felis DNA (Fig. 4A, lane 5). Although cross-reactivity with B. bacilliformis was noted, sequencing of the amplified fragment identified the genus for the bacillary angiomatosis isolates as rochalimaea. No amplification product was obtained with the use of each primer pair with DNA simultaneously extracted and amplified from the tissue from a control patient (data not shown) or in the absence of the DNA template (Fig. 4A, lane 8). PCR amplification of DNA extracted from biopsy tissue obtained surgically from the deep thigh mass of Patient 1 eight months before the diagnosis of bacillary angiomatosis produced a fragment of approximately 300 bp, but DNA extracted from the control patient did not (Fig. 4B). This finding strongly suggests that R. quintana was present at the time of the surgical biopsy, many months before diagnosis of bacillary angiomatosis.Amplification of the citrate synthase gene in the specimens from Patients 1, 2, and 4, followed by digestion with several restriction endonucleases, produced a pattern identical to that reported for R. quintana by Regnery et al.11 (data not shown), which corroborated the speciation determined by 16S rDNA sequencing.
DNA Sequencing
The amplified 16S rDNA product contained 241 bp between the priming oligonucleotides. The sequence of this fragment in specimens from Patients 1, 2, and 4 was identical to that of R. quintana: these sequences contained the expected 4-bp changes present in the corresponding region of R. henselae. The 3 nucleotide differences clustered among 10 contiguous nucleotides are underlined in Table 1. To document further that the organisms isolated were R. quintana, the entire 16S rDNA of isolates from Patients 1 and 2 was sequenced and was identical to R. quintana. The sequence of the 241-bp 16S rDNA fragment of the isolate from Patient 3 was identical to the type strain of R. henselae. Multiple clones from each isolate recovered from different sites in a single patient (separate punch biopsies and blood samples) were always found to be the same species.
Discussion
Cutaneous bacillary angiomatosis in HIV-seropositive patients has been reported with increasing frequency. Definitive identification of the causative organism requires culture of the bacillus from lesions of cutaneous bacillary angiomatosis. Isolation and propagation of these bacilli from cutaneous lesions have been attempted without success by many laboratories. Cockerell et al.22 isolated small, pleomorphic, fastidious, gram-negative bacilli from cutaneous lesions of bacillary angiomatosis in two patients, but they were unable to propagate the organisms on solid agar or provide definitive identification. In contrast, R. henselae has been readily isolated from blood with the use of lysis—centrifugation tubes.13 We isolated and propagated a rochalimaea species from cutaneous lesions in four HIV-infected patients and from the blood of two of the four patients and established the genus and species of the isolates by sequencing the amplified 16S rDNA. Surprisingly, R. quintana was isolated from three of the patients and R. henselae from the fourth, which indicates that two rochalimaea species are associated with cutaneous bacillary angiomatosis infection.
Two methods were used to recover organisms from the four biopsy specimens: direct plating on solid agar and cultivation in the presence of an endothelial-cell monolayer (Table 1). Despite the large number of R. quintana bacilli seen on electron microscopy in the tissue of Patient 1, no organisms grew from the initial plating of the homogenate, yet confluent colonies could be recovered on solid agar after 36 days of cultivation in the presence of an endothelial-cell monolayer. The facilitated recovery of a bacterium on solid agar after cultivation with eukaryotic cells has also been reported for A. felis. 23 Rochalimaea species may exist in different forms, requiring a period of adaptation in contact with endothelial cells in an environment similar to that in vivo, where rochalimaea organisms cluster in the interstitium among proliferating endothelial cells.24 The growth and morphology of endothelial cells also appeared to be altered by infection with rochalimaea species to resemble that described for endothelial cells exposed to angiogenesis factors in vitro,25 paralleling the striking angiogenesis observed in bacillary angiomatosis lesions in vivo. The deep lesions from two patients infected with R. quintana demonstrated macroscopic vascularity. Interestingly, the recurrence of R. quintana in Patient 2 presented as venous thrombosis of the upper extremity, apparently yet another vascular manifestation of rochalimaea infection.
Definite association of R. quintana with cutaneous bacillary angiomatosis has not been reported previously, although Relman et al.5 noted that the 241-bp 16S rDNA sequence from the cutaneous lesion of one of their four patients was identical to R. quintana. They suggested a Taq DNA polymerase error as a reason for the deviation of the sequence. R. quintana has been known to cause disease in humans since 1916, when a louse-borne epidemic of trench fever wreaked havoc on the troops of both sides in World War I.26 Trench fever had not been reported in the United States before the 1990s, and R. quintana infection has never before been associated with vascular or cutaneous lesions, despite the fact that many troops and researchers were naturally or experimentally infected with R. quintana and remained untreated and closely observed for long periods.26 , 27
Although either R. quintana or R. henselae was isolated from lesions of cutaneous bacillary angiomatosis in our patients, the reservoir and vector for the transmission of these contemporary rochalimaea infections remain unknown. Epidemiologic data based on 48 patients with bacillary angiomatosis or bacillary peliosis28 suggest that both a cat bite and a cat scratch are strong risk factors for this disease. Patient 3, the only patient infected with R. henselae, also was the only patient who had been exposed to cats. He had a primary inoculation site on his legs and a large inflammatory ipsilateral inguinal lymph node. Rochalimaea infection may be another cause of cat scratch disease, in addition to A. felis. Alternatively, it may be transmitted by an arthropod, such as the cat flea.
The ability to identify definitively the organisms causing bacillary angiomatosis with PCR and culture enables us to make important clinical observations about the spectrum and course of cutaneous bacillary angiomatosis. First, the disease can be very indolent in HIV-infected patients, and cutaneous lesions may be present months before a diagnosis is made. Second, relapse may occur despite prolonged antibiotic therapy. Third, cutaneous bacillary angiomatosis represents the clinically apparent manifestation of a systemic disease, as substantiated by the simultaneous culture of R. quintana from cutaneous lesions and blood. In addition, a systemic, toxic response resembling a Jarisch—Herxheimer reaction was observed in Patients 3 and 4 after they received the first several doses of an appropriate antibiotic.29 Both of these patients had a negative syphilis test. Kemper et al.30 described a similar toxic reaction after the first two doses of doxycycline in a patient with bacillary peliosis hepatis that was attributed to an adverse drug reaction. In addition to syphilis, the Jarisch—Herxheimer reaction has been described for leptospirosis, borreliosis, and brucellosis.31 Thus, immunodeficient patients may require indefinite antibiotic therapy and pretreatment with antipyretic agents to attenuate any Jarisch—Herxheimer reaction.
Finally, the appearance of the cutaneous lesions of bacillary angiomatosis may be remarkably diverse both clinically and histopathologically. All our patients had at least one nondiagnostic biopsy, despite evaluation by one or more of us; repeated biopsies were performed because of a strong clinical suspicion of bacillary angiomatosis. These atypical lesions were less vascular than usual and predominantly necrotizing. When histopathological evaluation fails to render a diagnosis, the use of other diagnostic methods, such as PCR and culture, may be successful. In addition to R. henselae and R. quintana, other as yet unidentified species may be isolated from cutaneous lesions of bacillary angiomatosis, and the study of these isolates will also provide valuable information about the unusual angiogenesis associated with cutaneous infection with R. quintana and R. henselae.
Supported by funds from the University of California—San Francisco (UCSF) AIDS Clinical Research Center and the John D. and Catherine T. MacArthur Foundation (to Dr. Koehler). Dr. Tappero is the recipient of a research fellowship from the Dermatology Foundation, UCSF, and was the recipient of a National Research Service Award in Dermatology (AR07175–15).
We are indebted to Dr. Richard S. Stephens and Dr. W. Keith Hadley for stimulating discussion and to Dr. Edward L. Murphy for providing patient data.
Source Information
From the Departments of Medicine and Laboratory Medicine (J.E.K.), Dermatology (T.G.B., P.E.L., J.W.T.), and Pathology (P.E.L.), University of California—San Francisco, San Francisco, and the Meningitis and Special Pathogens Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta (F.D.Q.). Address reprint requests to Dr. Koehler at Box 1204, University of California—San Francisco, San Francisco, CA 94143–1204.
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