Streptococcus milleri causing treatable infection in perineal hidradenitis suppurativa

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1 British Journal of Dermatology (1980) 103, 375. Streptococcus milleri causing treatable infection in perineal hidradenitis suppurativa A.S.HIGHET, R.E.WARREN*, R.C.D.STAUGHTONf AND S.O.B.ROBERTS Departments of Dermatology and * Bacteriology, Addenbrooke's Hospital, Cambridge Accepted for publication 6 March 1980 SUMMARY Streptococcus milleri was isolated from the active lesions of three patients with perineal hidradenitis suppurativa. In each patient, elimination of this organism by appropriate antibiotic therapy was accompanied by marked clinical improvement. Hidradenitis suppurativa is a chronic relapsing suppurative condition of apocrine gland follicles. Apocrinc glands usually open into pilosebaccous follicles, and occur normally in the skin of the axilla, buttocks, perineum, external genitalia, and breasts, and occasionally in other sites (Montagna, 1962). The pathogencsis of hidradenitis suppurativa is not well understood (Gordon, 1978, Roberts & Rook, 1979). The initial event is believed to be occlusion of the mouth of the apocrine gland follicle. The frequent presence of grouped comedones in affected areas suggests an underlying structural abnormality of the pilosebaccous unit. Inflammatory changes occur deep to the obstruction. In severe cases the gland is destroyed, and marked induration and scarring ensue with chronic sinus formation. The importance of bacterial infection is not clear. Staphylococcus aureus is sometimes isolated, and anaerobes have recently been implicated in axillary hidradenitis suppurativa (Leach et al., 1979). We report our preliminary findings implicating Streptococcus milleri in three patients with chronic severe hidradenitis suppurativa of the anogenital region, with an encouraging response to treatment. CASE REPORTS Case I Clinical details are shown in Table i. This 32-year-old man was referred for a final dermatological opinion before major surgery (Fig. i). He had suffered from hidradenitis suppurativa of the buttocks and natal cleft for 16 years. For 18 months painful abscesses had made sitting virtually impossible, and he had been unable to work for a year. Profuse purulent discharge rendered him housebound, and he had expressed suicidal intentions. Extensive immunological investigation had failed to reveal any defect of polymorph function or of humoral or cellular immunity. t Present Address: Department of Dermatology, Westminster Hospital, London S.W.r. O /8o/iooo-0375$02.oo C) 1980 British Association of Dermatologists 375

2 376 A.S.Highet et al. SI o 2 II c.s o S^^ ^o e no.5 DS y >>.s 2 t: u TI 2 u l 2 S e s S'«^» c o c e " «

3 Streptococcus milleri in hidradenitis suppurativa yii FIGURE I. Buttocks of Case i. TABLE 2. Previous streptococcal isolates from active lesions of Case r Date Streptococcal isolate Haemolytic Group G 'Nonhaemolytic' 'Microaerophilic' Haemolytic Group F erythromycin resistant 'Microaerophilic' I1.2.7S ^-Haemolytic not Group A, C, G erythromycin resistant Haemolytic Group F erythromycin resistant (see Table i)

4 *; 378 A.S.Highet ei al. 3?. 3 E p ~ C :- S 1. " S.O ".2 fq < c E c Cli Ecu' 3.2 o.2 ^ Qu. w

5 Streptococcus milleri in hidradenitis suppurativa 379 FIGURE 2. Vulva and perineum of Case 3, The unusual severity of the disease prompted careful bacteriological investigation leading to the isolation of Strep, milleri. A review of previous bacterial culture results suggested that this streptococeus had previously been repeatedly isolated, but its importance not recognized or its identity not specifically confirmed (Table 2). Case 2 Details shown in Table 3. This 32-year-oId man had a 12-year history of hidradenitis suppurativa of the pehanal skin and the medial aspects of both buttocks. There was much malodorous discharge and considerable pain. Case 3 Details shown in Table 4. The initial manifestations of hidradenitis suppurativa in this 31-year-old woman were recurrent abscesses in and around the breast areolae beginning at the age of 18. Five years later the vulva, groins, perineum, perianal region, and axillae became involved. During the period of our investigation, significant disease activity affected the vulva and perineum only (Fig. 2).

6 380 A.S.Highet et al. None of these three patients gave a family history of hidradenitis suppurativa, and none reported a personal or a family history of acne of unusual type or severity. DISCUSSION Leach ei al. (1979) reviewed their bacteriological findings in fifty-two patients with axillary abscess In twelve cases, all with axillary hidradenitis suppurativa, anaerobic bacteria, especially Gram-positive cocci, were isolated, but Strep, milleri was found in only one of these. Our experience in three consecutive cases of anogenital hidradenitis suppurativa is quite different in that Strep, milleri was isolated from aaive lesions in each patient. If this finding is confirmed, it would have important implications for treatment. Strep, milleri is a homogeneous biochemically defined taxon of streptococci (Lutticken et ai, 1978). The organism may be /?-, y-, or non-haemoljaic, although use of these terms may disguise the fact that an organism has not been identified to species level. Its growth on primary inoculation is often dependent on or enhanced by incubation in 5" carbon dioxide. It is not an obligate anaerobe and is metronidazole resistant. It has been termed Peptostreptococcus intermedius in many American papers, which is unfortunate, as the genus Peptostreptococcus is usually considered to be strictly anaerobic and metronidazole sensitive. When grown on blood agar Strep, milleri often has a characteristic caramel odour. The organism commonly carries Lancefield Group F antigen, although 'minute* strains of streptococci carrying the Lancefield Group A, C or G antigens, or no detectable Lancefield Group antigen, are also included in the taxon. Rapid Lancefield Grouping techniques for Group F streptococci have only recently become commercially available. Only Strep, milleri bearing Group F antigen were sought in the three patients we describe. Poole & Wilson (1979) detected Strep, milleri as a commensal in healthy subjects in the throat (3i%)> on extracted teeth (28%), in the vagina (18/;), and in the faeces (15/,,). It is now one of the commonest isolates from abscesses of brain (de Louvois, 1978), lung (Bartlett & Fincgold, 1972), pleura (Bartlett et al., 1974), liver (Sabbaj, Sutter & Finegold, 1972; Bateman, Eykyn & Phillips, 1975) and other intra-abdominal sites (Poole & Wilson, 1976). In addition, it has been isolated in Meleney's synergistic bacterial gangrene (Meleney, 1931) and in our laboratory from patients with otitis media, paronychia, or pilonidal sinuses. There are no recent reports on its resistance to antibiotics. Our records based on susceptibility testing with discs of tetracycline (10 /jg), erythromycin (5 /jg), clindamycin (2 /(g) and penicillin (i unit) show the incidences of resistance in isolates from individual patients to be: tetracyclines 87 of 240= 36% resistant erythromycin 4 of 160 = 2-5% resistant clindamycin i of 92 = 1% resistant penicillin oof240= 0% resistant. However, as Case i illustrates, benzylpenicillin in high dosage, even when combined with an aminoglycoside, gentamidn, does not seem to be effective in eliminating the organism from these deep-seated dermal sinuses. The reason for this is not clear, but it is possible that the drug does not penetrate lesions well, either because of scarring or because of poor lipid solubility. In streptococci cross-resistance between erythromycin and clindamycin is the rule (Dixon & Lipinski, 1979), although resistance to these antibiotics is not common. Susceptibility testing of Gram-positive organisms to trimethoprim is often not reproducible between laboratories and may therefore not be a reliable guide to therapy.

7 Streptococcus milleri in hidradenitis suppurativa 381 In each of these three cases of perineal hidradenitis suppurativa, at a time of active disease with marked tenderness and purulent discharge, Strep, milleri was isolated as the predominant or only bacterium from lesional pus. Case 2 was on no antibiotic when investigated. In each of Cases i and 3 the Strep, milleri initially found was resistant to the antibiotics then being given, namely clindamycin (and, of course, metronidazole) in Case i, and doxycycline in Case 3. Administration of an antibiotic to which the patient's organism was sensitive was followed by marked improvement in each case; in Case I doxycycline appears to have been the most effective drug, and Case 3 improved on erythromycin. It was noted, however, that lesions in Case i subsequently yielded Strep, milleri, a strain now resistant to tetracyclines, as well as to erythromycin and clindamycin, without clinical relapse. It is interesting that the best results were in Cases i and 2 in whom Strep, milleri was eliminated from the stool following oral vancomycin (with neomycin to obtain bactericidal synergy and nystatin to prevent candidiasis). In Case 3, the organism was not found in the faeces initially and vancomycin was not given. This patient relapsed soon after stopping erythromycin and her stool was then found to contain Strep, milleri. It may be that treatment aimed at eliminating Strep, milleri from the gut should be given even if the initial stool culture is negative. A simple regimen seems desirable and the agent used should not select for a resistant flora. If subsequent work suggests that elimination of Strep, milleri from the gut is indeed necessary for effective therapy of hidradenitis suppurativa infected with that organism, vancomycin alone may be useful. Our addition of neomycin and nystatin may prove to be unnecessary. Vaginal carriage may require separate treatment. FURTHER FINDINGS Our investigations have now included a further ten patients with active anogenital hidradenitis suppurativa. In five of these ten cases. Strep, milleri was isolated from lesions as the predominant organism. CONCLUSION These preliminary observations suggest that infection with Strep, milleri, a frequent commensal in the gastrointestinal and female genital tracts, may cause readily treatable acute exacerbations in chronic hidradenitis suppurativa of the anogenital region. The simplest explanation is that the organism gains access to pre-existing sinuses in areas of scarring. We have not studied the possible role of Strep, milleri in the early stages of hidradenitis suppurativa. Routine laboratory methods may fail to provide accurate identification of Strep, milleri, and collaboration between clinician and bacteriologist is advised. Sensitivity testing (to erythromycin and tetracyclines in particular) should permit effective treatment of these acute exacerbations. Strep, milleri appears to be less important in axillary hidradenitis suppurativa (Leach et al., 1979) and it seems likely that perineal lesions are more readily colonzied from the gut or the vagina. Treatment aimed at eliminating the organism from the flora appears logical, but we have insufficient evidence at present to confirm its value. REFERENCES BARTLETT, J.G. & FINEGOLD, S.M. (1972) Anaerobic pleuropulmonary infections. Medicine, 51, 413. BARTLETT, J.G., GORBLACH, S.L., THADEPALLI, H. & FINEGOLD, S.M. (1974) Bacteriology of empyema. Lancet, i, 338. BATEMAN, N.T., EYKYN, S. & PHILLIPS, I. (1975) Pyogenic liver abscess caused by Streptococcus milleri. Lancer, i, 657.

8 382 A.S.Highet et al. DIXON, J.M.S. & LiPiNSKi, A.E. (1979) Prevalence of antibiotic resistance in pneumococci and Group-A streptococci. In: Pathogenic Streptococci {Proceeding of Vllth International symposium on streptococci and streptococcal diseases) (Ed, by M.T. Parker), p Rcedbooks, Chertsey, Surrey. GORDON, S.W. (1978) Hidradenitis suppurativa: a closer look. Journal of the National Medical Association, 70, 339- LEACH, R.D., EYKYN, SJ., PHILLIPS, I., CORRIN, B. & TAYLOR, E.A. (1979) Anaerobic axillary abscess. British Medical Journal, ii, 5. DE Louvois, J. (1978) The bacteriology and chemotherapy of brain abscess. Journal of Antimicrobial Chemotherapy, 4, 395. LOTTICKEN, R., WENDORFF, U., LOTTICKEN, D., JOHNSON, E.A. & WANNAMAKER, L.W. (1978) Studies on streptococci resembling Streptococcus milleri and on an associated surface-protein antigen. Journal of Medical Microbiology, 11, 419. MELENEY, F.L. (i93r) Bacterial synergism in disease processes. Annals of Surgery, 94, 961. MONTAGNA, W. (1962) The apocrine sweat glands. In: The Structure and Function of Skin, p Academic Press, New York. PooLE, P.M. & WILSON, G. C1976) Infection with minute-colony-form ing y?-haemolytic streptococci. Journal of Clinical Pathology, 29, 740. PoOLE, P.M. & WILSON, G. (1979) Occurrence and cultural features of Streptococcus milleri in various body sites. Journal of Clinical Pathology, 32, 764. ROBERTS, S.O.B. & ROOK, A.J. (1979) Suppurative hidradenitis. In: Textbook of Dermatology (cd. by A, J. Rook, D.S. Wilkinson and F.J.G. Ebling), 3rd edn, p Blackwell Scientific Publications, Oxford. SABBAJ, J., SUTTER, V.L. & FINEGOLD, S.M. (1972) Anaerobic pyogenic liver abscess. Annals of Internal Medidnt^ 77> 629.

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