By Richard R. Watkins, MD, MS, FACP, FIDSA
Associate Professor of Internal Medicine, Northeast Ohio Medical University; Division of Infectious Diseases, Cleveland Clinic Akron General, Akron, OH
Dr. Watkins reports that he has received research support from Allergan.
SYNOPSIS: Using metagenomic techniques, investigators determined that two Gram-negative anaerobes, Prevotella and Porphyromonas, predominate in hidradenitis suppurativa lesions. Two others, Fusobacterium and Parvimonas, correlate with disease severity.
SOURCE: Guet-Revillet H, Jais JP, Ungeheuer MN, et al. The microbiological landscape of anaerobic infections in hidradenitis suppurativa: A prospective metagenomic study. Clin Infect Dis 2017;65:282-291.
Hidradenitis suppurativa (HS) is an incompletely understood and challenging condition for clinicians to manage. The pathogenesis of HS is believed not to be infectious per se, but, rather, to be a chronic inflammatory disease of the terminal hair follicle that predisposes the patient to recurrent skin infections. Guet-Revillet et al hypothesized that anaerobic bacteria are the main drivers of this inflammation and, through the use of molecular techniques, aimed to comprehensively elucidate the microbiology of HS skin lesions.
Severity of HS is based on the Hurley scale: Stage 1 consists of a single lesion or abscess, stage 2 denotes multiple lesions with sinus tracts and scarring, and stage 3 is severe disease with multiple interconnected sinus tracts across an entire area of skin. The investigators prospectively sampled and cultured lesions in 149 patients with different Hurley stages and 175 unaffected samples, which were used as controls. Draining lesions were sampled by swabbing pus, while nondraining lesions were sampled by punch biopsy or needle aspiration. The DNA from the cultured bacteria was extracted and used to construct 16S rRNA gene libraries. High-throughput sequencing then was performed to compare the microbiome of 80 HS lesions to that of 88 control samples.
Anaerobic flora were isolated in 83% of the HS lesions compared to 53% of the controls. In a breakdown by Hurley stage, anaerobes were seen in 54% of stage 1 lesions, 95% in stage 2 lesions, and 100% in stage 3 lesions. Streptococcus dysgalactiae, an opportunistic skin pathogen, was isolated from the HS samples but not from the controls. Staphylococcus aureus was cultured from some of the HS lesions but was never the predominant organism. Moreover, skin commensals like Staphylococcus epidermidis and Micrococcus spp. were less abundant in the HS lesions than in the controls. High-throughput sequencing identified 43 taxa that were associated with HS lesions, of which Prevotella, Porphyromonas, Fusobacterium, and Parvimonas were the most common. Hurley stage 3 lesions exhibited an increased bacterial diversity compared to stage 1 and 2 lesions, of which the most abundant taxa were Fusobacterium, Parvimonas, Streptococcus, and Clostridiales. The microbiome of the HS lesions did not vary according to gender, duration, family history of HS, body mass index, location of the lesion(s), or clinical parameters except for Hurley stage.
COMMENTARY
These data are interesting because they represent the most comprehensive analysis of the microbiology of HS lesions to date. The two most common bacteria isolated from the HS lesions, Prevotella and Porphyromonas, usually are commensals in the mouth and vagina. However, they also are associated with chronic infections like gingivitis and periodontitis. Fusobacterium, the most common isolate from Hurley stage 3 lesions, is another commensal in both the mouth and gastrointestinal tract that has been associated with neonatal sepsis, chorioamnionitis, inflammatory bowel disease, and appendicitis. As the authors note, Fusobacterium has proinflammatory properties like strong adhesion to epithelial cells, the ability to invade tissues, and biofilm formation that may contribute to the inflammation in HS lesions. These anaerobes overall exhibit lower pathogenicity compared to other skin organisms, such as S. aureus. Thus, this may explain the lack of a systematic inflammatory response to HS. Regarding the limitations of the study, it was conducted at a single institution, so the results might not be generalizable to other settings. Also, the investigators collected samples from 149 HS lesions but only analyzed 80 of them, which may have led to selection bias.
So how can the findings of the study be used in clinical practice? Previous investigations have shown that antibiotics with anaerobic activity (e.g., carbapenems) can lead to clinical improvement in HS and, in some cases, remission. TNF-α blockers also have been used successfully to reduce inflammation. Guet-Revillet et al provide a theoretical basis to support the use of antibiotics in the treatment of HS. Further clinical studies are warranted to determine if this approach is indeed efficacious. These studies should be designed to compare commonly prescribed antibiotics (e.g., clindamycin, amoxicillin-clavulanate) vs. placebo in a randomized, blinded fashion. In my practice, I have had some success in treating patients with HS using topical clindamycin, although recurrences unfortunately are common. I also prescribe zinc, which has anti-inflammatory properties, and there is some evidence that 90 mg of zinc gluconate daily can reduce the size of HS lesions.
Using metagenomic techniques, investigators determined that two Gram-negative anaerobes, Prevotella and Porphyromonas, predominate in hidradenitis suppurativa lesions. Two others, Fusobacterium and Parvimonas, correlate with disease severity.
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