Trimethoprim/sulfamethoxazole and cephalexin combination therapy in hidradenitis suppurativa patients: A series of 16 cases

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful nodules, abscesses, and sinus tracts. Although systemic antibiotics are commonly used to manage HS,1Alikhan A. Sayed C. Alavi A. et al.North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hid adenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management.J Am Acad Dermatol. 2019; 81: 91-101https://doi.org/10.1016/j.jaad.2019.02.068Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar tetracycline monotherapy, which is often used as a first-line antibiotic treatment for HS, can be ineffective or poorly tolerated by patients. Combined antibiotic regimens such as clindamycin and rifampin have shown efficacy; however, data are overall limited. Herein, we present a single-center case series to better understand the efficacy and safety of trimethoprim/sulfamethoxazole (TMP/SMX) and cephalexin combination therapy in patients with HS. HS patients who presented to the University of California, Los Angeles dermatology division between January, 2015 and December, 2021 were identified using International Classification of Diseases (ICD)-9 705.83 and ICD-10 L73.2 codes. Patients were included if they were 18 years of age or older, started on TMP/SMX ± cephalexin, and had a 3-month follow-up visit after initiation of treatment. A retrospective chart review was performed to collect data on patient characteristics, comorbidities, drug dosages, physician and patient assessed response to treatment at 3 months (based on whether the physician or patient reported improvement compared to baseline visit), and adverse effects. Sixteen patients (mean age: 38.1, standard deviation: 15.2, range: 19-67) met the inclusion criteria (Table I). Most patients had Hurley stage II (43.8%) and III (50%) disease. After 3 months, 75% (12/16) and 68.8% (11/16) had improvement based on physician and patient report, respectively. Adverse events were reported in 2 patients including diarrhea and a pruritic rash on the trunk and arms.Table ICharacteristics and treatment responses of patients treated with trimethoprim/sulfamethoxazole and cephalexinPatient numberAge, gender, and BMIComorbiditiesBaseline Hurley stagePreviously failed treatmentsConcomitant treatmentsTMP/SMX doseCephalexin dosePhysician assessed improvement at 3 months?Patient assessed improvement at 3 months?119 F, 46.8ADHD, anxiety, depression, and obesityIIICiprofloxacin, doxycyclineTopical abx, ILK, and surgical excision800-160 mg twice a day500 mg twice a dayYesYes221 F, 27.4NoneIITopical abx, laser hair removalTopical abx, ILK800-160 mg twice a day500 mg twice a dayNoNo322 FPilonidal cystIITopical abx, clindamycin, doxycycline, minocycline, rifampin, ADA, OCPs, spironolactone, prednisone, and ILKTopical abx, ADA, OCPs, spironolactone, and ILK800-160 mg daily500 mg twice a dayNoNo422 M, 34.9Acne, DCSIICephalexin, clindamycinTopical abx800-160 mg twice a day500 mg twice a dayNoNo524 F, 48.4ObesityIIITopical abx, cephalexin, minocycline, and ILKTopical abx800-160 mg twice a day500 mg twice a dayNoNo631 FAcneIITopical abx, minocyclineTopical abx, ILK800-160 mg twice a day500 mg twice a dayYesYes732 F, 26.1AnxietyITopical abx, doxycycline, and ILKTopical abx, OCPs800-160 mg twice a day500 mg twice a dayYesYes838 F, 34Acne, AD, anxiety, depression, hirsutism, HLD, obesity, PCOS, and prediabetesIITopical abx, OCPs, spironolactone, prednisone, and surgical excisionTopical abx, OCPs, and spironolactone800-160 mg twice a day500 mg twice a dayYesYes938 F, 30.7ObesityIIITopical abx, clindamycin, rifampin, and ILKTopical abx800-160 mg twice a day500 mg twice a dayYesYes1039 MAcne, obesity, and prediabetesIIIClindamycin, doxycycline, prednisone, ILK, and I&DTopical abx800-160 mg twice a day500 mg twice a dayYesNo1141 M, 32.9Acne, anemia, anxiety, depression, DM, HLD, and obesityIIITopical abx, cephalexin, clindamycin, doxycycline, prednisone, and surgical excisionTopical abx, ADA, and ILK800-160 mg twice a day500 mg twice a dayYesYes1245 F, 28.4NoneIIITopical abx, clindamycin, doxycycline, and rifampinTopical abx800-160 mg twice a day500 mg twice a dayYesYes1351 F, 35Acne, depression, HLD, obesity, and prediabetesIITopical abx, doxycycline, isotretinoin, and ILKTopical abx, ILK, and surgical excision800-160 mg twice a day500 mg twice a dayYesYes1456 M, 28.3Acne, DMIIITopical abx, clindamycin, doxycycline, and ILKTopical abx, acitretin, and ILK800-160 mg twice a day500 mg twice a dayYesYes1563 M, 24Acne, anemia, depression, and HLDIIITopical abx, clindamycin, doxycycline, metronidazole, isotretinoin, ILK, I&D, and surgical excisionTopical abx400-80 mg twice a day250 mg twice a dayYesYes1667 FAcne, depression, and thyroid disorderIIMinocycline, a different tetracycline, ILK, and surgical excisionTopical abx400-80 mg twice a day250 mg twice a dayYesYesabx, Antibiotics; AD, atopic dermatitis; ADA, adalimumab; ADHD, attention-deficit/hyperactivity disorder; BMI, body mass index; DCS, dissecting cellulitis of the scalp; DLQI, dermatology life quality index; DM, diabetes mellitus; F, female; HLD, hyperlipidemia; I&D, incision and drainage; IFX, infliximab; ILK, intralesional Kenalog; M, male; mg, milligram(s); OCPs, oral contraceptives; PCOS, polycystic ovarian syndrome. Open table in a new tab abx, Antibiotics; AD, atopic dermatitis; ADA, adalimumab; ADHD, attention-deficit/hyperactivity disorder; BMI, body mass index; DCS, dissecting cellulitis of the scalp; DLQI, dermatology life quality index; DM, diabetes mellitus; F, female; HLD, hyperlipidemia; I&D, incision and drainage; IFX, infliximab; ILK, intralesional Kenalog; M, male; mg, milligram(s); OCPs, oral contraceptives; PCOS, polycystic ovarian syndrome. Our case series found that TMP/SMX and cephalexin may be an efficacious combination antibiotic regimen for patients with Hurley stage II/III HS, including those who had previously tried other oral antibiotics. Oral antibiotics are frequently used treatments for HS.1Alikhan A. Sayed C. Alavi A. et al.North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hid adenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management.J Am Acad Dermatol. 2019; 81: 91-101https://doi.org/10.1016/j.jaad.2019.02.068Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar Most antibiotic regimens are given for a 3-month period to improve pain and drainage and decrease the frequency of new lesions in the short-term. In addition, they can serve as a bridge to other treatments for HS such as biologics and surgery. Dual antibiotic therapy is part of the management guidelines for HS and the majority of data has been published on clindamycin and rifampin, which has shown benefit.2Hendricks A.J. Hsiao J.L. Shi V.Y. Overview and comparison of hidradenitis suppurativa management guidelines.in: A comprehensive guide to Hid adenitis Suppurativa. Elsevier, 2022: 130-144https://doi.org/10.1016/B978-0-323-77724-7.00014-0Crossref Scopus (0) Google Scholar,3Mendonça C.O. Griffiths C.E.M. Clindamycin and rifampicin combination therapy for hidradenitis suppurativa: hidradenitis suppurativa therapy.Br J Dermatol. 2006; 154: 977-978https://doi.org/10.1111/j.1365-2133.2006.07155.xCrossref PubMed Scopus (180) Google Scholar A retrospective study of 34 patients receiving oral clindamycin and rifampicin combination therapy found that 28 (82.4%) had partial or complete improvement.4van der Zee H.H. Boer J. Prens E.P. Jemec G.B.E. The effect of combined treatment with oral clindamycin and oral rifampicin in patients with hidradenitis suppurativa.Dermatology. 2009; 219: 143-147https://doi.org/10.1159/000228337Crossref PubMed Scopus (180) Google Scholar However, clindamycin commonly causes gastrointestinal issues, and the use of rifampin is often limited by its potential interactions with other medications. Clostridium difficile infection has been reported with the use of clindamycin and rifampin medication combination in HS.5Bessaleli E. Scheinfeld N. Clostridium difficile arising in a patient with hidradenitis suppurativa on clindamycin and rifampin.Dermatol Online J. 2018; 24 (13030/qt3x20x5rj. https://doi.org/10.5070/D3245040147)Crossref Google Scholar TMP/SMX and cephalexin are broad-spectrum antimicrobial agents with anti-inflammatory properties and together, they may have a synergistic effect against many of the gram-positive and gram-negative bacteria which have been isolated from inflammatory lesions in HS.6Hessam S. Sand M. Georgas D. Anders A. Bechara F.G. Microbial profile and antimicrobial susceptibility of bacteria found in inflammatory hidradenitis suppurativa lesions.Skin Pharmacol Physiol. 2016; 29: 161-167https://doi.org/10.1159/000446812Crossref PubMed Scopus (37) Google Scholar Our study contributes to the literature by providing novel efficacy data on TMP/SMX and cephalexin combination therapy for patients with HS, showing benefit in patients with moderate-to-severe disease. Limitations of this study include a small sample size from a single center and its retrospective nature. Moreover, the use of concomitant therapies may have influenced treatment outcomes. Larger studies that compare efficacy rates between different antibiotic regimens and the efficacy of monotherapy versus combination antibiotics are needed. Dr Hogeling has been an investigator for Celgene and Amgen. Dr Shi is on the board of directors for the Hidradenitis Suppurativa Foundation (HSF), an advisor for the National Eczema Association, is a stock shareholder of Learn Health, and has served as an advisory board member, investigator, speaker, and/or received research funding from Sanofi Genzyme, Regeneron, AbbVie, Genentech, Eli Lilly, Novartis, SUN Pharma, LEO Pharma, Pfizer, Incyte, Boehringer Ingelheim, Alumis Aristea Therapeutics, Menlo Therapeutics, Dermira, Burt’s Bees, Galderma, Kiniksa, UCB, Target-PharmaSolutions, Altus Lab/cQuell, MYOR, Polyfins Technology, GpSkin, and Skin Actives Scientific. Dr Hsiao is on the Board of Directors for the Hidradenitis Suppurativa Foundation, has served as a consultant for Aclaris, Boehringer Ingelheim, Novartis, and UCB, and has served as a consultant and speaker for AbbVie. There was no financial transaction for the preparation of this manuscript. All other authors report no conflicts of interest.

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