Advertisement

Updates in therapeutics for folliculitis decalvans: A systematic review with evidence-based analysis

Published:August 06, 2018DOI:https://doi.org/10.1016/j.jaad.2018.07.050
      To the Editor: Folliculitis decalvans (FD) is the most common neutrophilic scarring alopecia, causing painful, recurrent purulent follicular exudation.
      • Miguel-Gomez L.
      • Vano-galvan S.
      • Perez-garcia B.
      • Carrillo-gijon R.
      • Jaen-olasolo P.
      Treatment of folliculitis decalvans with photodynamic therapy: results in 10 patients.
      Currently, there is a paucity of data regarding the efficacy of FD-specific treatments. This study aimed to provide an evidence-based analysis of current treatment efficacy for FD. Using PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) guidelines. PubMed, Medline, Scopus, and the Cochrane library were searched for articles published in English during 1998-2018. Data regarding treatment regimen and efficacy was graded according to the American College of Physicians grading system (Supplemental Fig 1; available at http://www.jaad.org).
      • Qaseem A.
      • Snow V.
      • Owens D.K.
      • Shekelle P.
      The development of clinical practice guidelines and guidance statements of the American College of Physicians: summary of methods.
      , Treatment efficacy of FD was discussed in 20 studies that included 282 patients, of which 73.4% were male. The highest level of evidence was grade 3, encompassing 7 studies with 263 patients (Table I).
      • Vano-Galvan S.
      • Molina-Ruiz A.M.
      • Fernandez-Crehuet P.
      • et al.
      Folliculitis decalvans: a multicentre review of 82 patients.
      • Powell J.J.
      • Dawber R.P.
      • Gatter K.
      Folliculitis decalvans including tufted folliculitis: clinical, histological and therapeutic findings.
      • Miguel-Gomez L.
      • Rodrigues-Barata A.R.
      • Molina-Ruiz A.
      • et al.
      Folliculitis decalvans: effectiveness of therapies and prognostic factors in a multicenter series of 60 patients with long-term follow-up.
      • Tietze J.K.
      • Heppt M.V.
      • von Preussen A.
      • et al.
      Oral isotretinoin as the most effective treatment in folliculitis decalvans: a retrospective comparison of different treatment regimens in 28 patients.
      • Bunagan M.J.K.
      • Banka N.
      • Shapiro J.
      Retrospective Review of folliculitis decalvans in 23 patients with course and treatment analysis of long-standing cases.
      • Aksoy B.
      • Hapa A.
      • Mutlu E.
      Isotretinoin treatment for folliculitis decalvans: a retrospective case-series study.
      A multicenter, retrospective study showed that 15 patients treated with a 10-week course of clindamycin and rifampicin achieved the longest disease remission at an average of 7.2 months. The remission period was shorter among those treated with doxycycline or azithromycin for 3-6 months, who subsequently received adjunct topical antibiotics and intralesional corticosteroids.
      • Vano-Galvan S.
      • Molina-Ruiz A.M.
      • Fernandez-Crehuet P.
      • et al.
      Folliculitis decalvans: a multicentre review of 82 patients.
      Powell et al demonstrated that a 10-week course of clindamycin and rifampicin achieved remission in 10 of 18 (55.6%) patients for 2-22 months, and 5 additional patients responded after 2-3 more courses.
      • Powell J.J.
      • Dawber R.P.
      • Gatter K.
      Folliculitis decalvans including tufted folliculitis: clinical, histological and therapeutic findings.
      Similarly, Miguel Gomez et al demonstrated a 91% response rate and longer duration of response (5 months) in cases initially refractory to tetracycline treatment.
      • Miguel-Gomez L.
      • Rodrigues-Barata A.R.
      • Molina-Ruiz A.
      • et al.
      Folliculitis decalvans: effectiveness of therapies and prognostic factors in a multicenter series of 60 patients with long-term follow-up.
      Conversely, a retrospective study by Tietze et al showed 8 of 12 patients treated with a 10-week course of clindamycin and rifampicin relapsed, and 2 had no clinical response.
      • Tietze J.K.
      • Heppt M.V.
      • von Preussen A.
      • et al.
      Oral isotretinoin as the most effective treatment in folliculitis decalvans: a retrospective comparison of different treatment regimens in 28 patients.
      In another retrospective study, 7 of 10 patients treated with combination tetracycline, clobetasol propionate lotion, and intralesional triamcinolone for an average of 7 months were in disease remission for up to 4 years. Continued treatment with oral antibiotics, intralesional triamcinolone, or clobetasol propionate was needed in 11 of 23 patients to maintain remission.
      • Bunagan M.J.K.
      • Banka N.
      • Shapiro J.
      Retrospective Review of folliculitis decalvans in 23 patients with course and treatment analysis of long-standing cases.
      Tietze et al
      • Tietze J.K.
      • Heppt M.V.
      • von Preussen A.
      • et al.
      Oral isotretinoin as the most effective treatment in folliculitis decalvans: a retrospective comparison of different treatment regimens in 28 patients.
      demonstrated that isotretinoin treatment for 5-7 months resulted in disease remission for 4-24 months in 9 of 10 patients, 3 of whom required low-dose maintenance. Of note, treatment of FD with isotretinoin was associated with hyperlipidemia (14/39) in another retrospective review.
      • Aksoy B.
      • Hapa A.
      • Mutlu E.
      Isotretinoin treatment for folliculitis decalvans: a retrospective case-series study.
      Table IGrade 3 studies with low quality of evidence
      Study design, studyPrevious treatment failureCohort descriptionTreatment regimenTreatment adverse effectsTreatment outcomeOutcome from ACP grading
      1) Retrospective, multicenter review [Vano-Galvan et al; J Eur Acad Dermatol Venereol. 2015; 29(9):1750-57]Not mentioned82 total patients; 52 were men; mean age 35 y; 17 (21%) had severe disease39 patients doxycycline for 3-6 monNoneDoxycycline: 90% improvement, remission (mean 4.8 mon)Grade 3
      15 patients clindamycin and rifamicin for 10 wkClindamycin and rifampicin: 100% improvement, remission (mean 7.2 mon)
      6 patients azithromycin 3x/wk for 3 monAzithromycin: 100% improvement, remission (mean 4.6 mon)
      2) Retrospective, single-center, observational study [Tietze et al; J Eur Acad Dermatol Venereol 2015; 29(9):1816-21]Clindamycin, rifampicin, clarithromycin, dapsone28 total patients; 26 were men; age range 19-64 yIST (0.2-0.5 mg/kg) for 5-7 monNoneComplete remission with IST in 9 (90%) patients for 4 mon-2 yGrade 3
      Dosage tapered after remission achieved to 10 mg 2-3x/wk in 3 patients3 (30%) patients required maintenance on low-dose IST
      Follow-up range 2 mon-15 yRelapse rates with antimicrobials: clindamycin and rifampicin 8 (80%) patients, clarithromycin 6 (67%) patients, ciprofloxacin or doxycycline 7 (78%) patients, dapsone 4 (57%) patients
      3) Retrospective, single-center, observational study [Bunagan et al; J Cutan Med Surg. 2015; 19(1):45-9]Not mentioned23 total patients; 6 men; follow-up period 3 mon-13 yA. ILT + clobetasol propionate lotion + (doxycycline 100 mg bid, minocycline 100 mg bid, or tetracycline 500 mg bid) (n = 10)NoneA. FD in remission in 7/10 (70%) patients, treatment discontinued
      • FD inactive in 3 (30%) patients with continued treatment
      Grade 3
      B. Cephalexin + ILT + clobetasol propionate lotion (n = 6)
      C. Clindamycin + rifampicin (n = 1)B. FD inactive in 6/6 patients with continued treatment
      D. ILT + clobetasol propionate lotion (n = 1)C. FD in remission in 1/1 patient, treatment discontinued

      D. FD in remission in 1/1 (100%) patient, treatment discontinued (The ILT+clobetasol proprionate lotion n=1 line)
      E. Multiple combinations (cephalexin, minocycline, tetracycline, rifampicin, clindamycin, ciprofloxacin, IST, dapsone) (n = 5)E. FD under control in 2/5 (40%) patients with continued treatment, FD still active in 3/5 (60%) patients despite treatment
      4) Single-center case series; nonblinded, nonrandomized study [Sillani et al; Int J Trichol Jan 2010; 2(1):20-3]Not reported13 total patients; 11 were male; mean age 30.1 (range 15-66) yMild FD (n = 8): minocycline 100 mg po bid1 patient developed nausea and vertigo from rifampicinMild FD: minocycline 100 mg bid for average of 5.7 wk cleared inflammatory scalp lesions in 7/8 patients, 1/8 needed 2-wk acitretin rescue therapy, 1/8 exhibited FD relapse after 8 monGrade 3
      Moderate FD: minocycline 100 mg po bid + rifampicin 150-300 mg bidModerate FD cases: combination of minocycline and rifampicin for average of 11.7 wk effective in treating 3 patients, clarithromycin + rifampicin for average of 10 wk effective in clearing scalp lesions in 2 patients (1 mild FD, 1 moderate FD)
      Adjuvant drugs used included topical fusidic acid or mupirocin, selenium sulfide shampoo, oral compound glycyrrhizin, and zinc gluconate9/13 patients partial hair growth responders (<75%)
      5) Case series study [Powell et al; Br J Dermatol. 1999; 140(2): 328-33]Flucoxacillin, erythromycin, minocycline18 total patients; 13 were men; age range 18-62 yClindamycin 300 mg bid and rifampicin 300 mg bid for 10 wk1 patient developed rash from clindamycinFD in remission for 2-22 mon in 10 (55.6%) patients after 10-week course; FD in remission in 15 (83.3%) patients after 2-3 more 10-week coursesGrade 3
      6) Retrospective, multicenter review [Miguel-Gomez et al; J Am Acad Dermatol. 2018; Epub ahead of print]Not reported60 total patients; 37 were men; median age 40 (range 23-83) yTopical steroids (n = 48), topical antibiotics (n = 37), tetracycline (n = 36), intralesional steroids (n = 25), rifampicin and clindamycin (n = 21), oral isotretinoin (n = 15), photodynamic therapy (n = 8), oral steroids (n = 5), azithromycin and dapsone (n = 4), topical tacrolimus (n = 3), hydroxychloroquine and minoxidil (n = 2)Epigastralgia, diarrhea, and headache associated with tetracyclines in 4 patients; hypercholesterolemia, arthralgias, and epistaxis in 3 patients treated with isotretinoinTetracyclines used in moderate and severe FD patients (n = 36) had 91% response rate; in refractory cases, rifampicin + clindamycin most effective, with 90.5% response rate and longer response duration (5 mon)Grade 3
      7) Retrospective, case series study [Aksoy et al; Int J Dermatol. 2018; 57(2):250-253]Not reported39 total patients, all male; mean age 37.85 (range 16-82) yOral isotretinoin 0.1-1.02 mg/kg/d for median 2.5 (range 1-8) mon; patients responding to treatment (n = 36) were subgrouped by daily dose (<0.4 mg/kg, ≥0.4 mg/kg) and duration (<3 mo, ≥3 mo)Hyperlipidemia (35.9%), intractable xerosis (10.3%)36 patients had partial and complete response after isotretinoin treatment, 61.5% patients had response to IST within 1 mon; 66% patients receiving IST <3 mo relapsed; patients that received oral IST ≥0.4 mg/kg/d for ≥3 mo had best response to IST, 66% no disease relapseGrade 3
      BID, Two times a day; FD, folliculitis decalvans; ILT, intralesional triamcinolone; IST, isotretinoin; po, per oral.
      Newer therapeutic options have been described in case reports and case series in recent years, and accordingly, the level of evidence is very low (grade 4) (Table II).
      • Miguel-Gomez L.
      • Vano-galvan S.
      • Perez-garcia B.
      • Carrillo-gijon R.
      • Jaen-olasolo P.
      Treatment of folliculitis decalvans with photodynamic therapy: results in 10 patients.
      Red light photodynamic therapy resulted in clinical improvement in 9 of 10 patients, with 6 patients exhibiting disease remission.
      • Miguel-Gomez L.
      • Vano-galvan S.
      • Perez-garcia B.
      • Carrillo-gijon R.
      • Jaen-olasolo P.
      Treatment of folliculitis decalvans with photodynamic therapy: results in 10 patients.
      Additional treatments with lowest evidence were tacrolimus ointment, external beam radiation, isotretinoin, human immunoglobulin, adalimumab, infliximab, and long-pulse neodymium:yttrium aluminum garnet.
      Table IIGrade 4 studies with very low level of evidence
      Study designPrevious treatment failurePatient descriptionTreatment regimenTreatment adverse effectsTreatment outcomeOutcome from ACP grading
      1) Retrospective, case report [Collier et al; Clin Exp Dermatol. 2017; doi: 10.1111/ced.13238]Doxycycline, rifampicin, clindamycin, IST, acitretin, CS, CsA26-year-old manSystemic PDT with ultraviolet light (100-140 J/cm2) with 1 mg/kg porfimer sodiumNoneFD in remission at 25 mon follow-upGrade 4
      2) Retrospective, case series [Burillo-Martinez et al; J Am Acad Dermatol. 2016;74(4): e69-70]Oral and intralesional CS, antibiotics3 patients; all men; mean age 30 yPDT; mean of 11 sessions over mean 9 mon; concurrent treatment with sulfamethoxazole-trimethoprimAll patients experienced pain and erythema; 1 patient exhibited worsening of condition2 patients mild improvement after PDT session but relapsed before next cycle; 1 patient worsening of FD during treatment, required oral CSGrade 4
      3) Retrospective, case report [Elsayad et al; Strahlenther Onkol. 2015; 191(11): 883-8]Tetracycline, rifampicin, cefaclor, clarithromycin, linezolid, CS, CsA, IST45-year-old manFirst course radiotherapy: 5 Gy in 5 fractions; second course radiotherapy: 6 Gy in 5 fractions 5 mon laterMild pain, erythema, and transient increased scalp exudateFD and associated symptoms significantly improved especially pain and pruritus at 12 mon follow-upGrade 4
      4) Prospective, single-center, case series [Miguel-Gomez et al; J Am Acad Dermatol. 2015;72(6): 1085-7]Doxycycline, IST, rifampicin10 patients; 5 menPDT with MAL (methyl aminolevulinate hydrochloride) 160 mg/g cream at 4-wk interval; area treated with red light at 630 nm with total light dose of 37 J/cm2; 2 patients concurrent doxycycline and intralesional CS6 (60%) patients experienced local reaction post-PDT and painFD in remission for 9 (90%) patients; duration of remission 2-36 months (mean 9.9 mon); No. of patients and (no. sessions): 1(13), 1(9), 1(6), 1(5), 3(4), 1(3)Grade 4
      5) Retrospective, case report [Ismail et al; J Dermatolog Treat 2015; 26(5):471-2]Clindamycin, rifampicin27-year-old manIVIG 2 g/kg first month then reduced to 1 g/kg from second to fourth month; concurrent flucloxacillin up to 3 infusionsNoneFD in remission at 6 mon follow-upGrade 4
      6) Retrospective, single-center, case series [Kreutzer et al; J Dtsch Dermatol Ges 2014;12(1): 74-6]Clindamycin, rifampicin, dapsone, methotrexate, oral CS, IST2 patients; all women; age 58 and 50 yAdalimumab 40 mg every 2 wkNoneFD in remission after 2-3 mon treatment; long-term follow-up unavailableGrade 4
      7) Case report [Meesters et al; J Dermatolog Treat 2014;25(2): 167-8]Tetracycline, erythromycin, doxycycline, flucloxacillin, IST34-year-old manLong-pulsed Nd:YAG 1064-nm laser; started at 30 J/cm2 for 50 ms; dose increased to 50 J/cm2 with reduced pulse duration to 30 ms; total of 9 treatments, 8–12-wk intervalPain and mild crusting but relived with topical lidocaine ointment and oral tramadol 50 mg during treatmentFD in remission at 1.5 y follow-upGrade 4
      8) Retrospective, case report [Mihaljevic et al; J Dtsch Dermatol Ges 2012;10(8): 589-90]IST, oral CS, oral antibiotics, dapsone and zinc45-year-old manInfliximab 5 mg/kg every 4-6 wkNoneFD in remission after 3 infusions until 12 mon follow-upGrade 4
      9) Retrospective, case report [Castano-Suarez et al; Photodermatol Photoimmunol Photomed. 2012;28(2): 102-4]Topical CS, IST, dapsone32-year-old womanPDT with MAL (methyl aminolevulinate hydrochloride); 630 nm delivered at 37 J/cm2; 3 cycles over 8-wk period; each cycle involved 2 treatments 2 wk apartMild itchingFD in remission at 12 mon follow-up after last treatmentGrade 4
      10) Retrospective, case series [Bastida et al; Int J Dermatol. 2012; 51(2): 216-20]Acitretin, dapsone, oral and topical CS, antibiotics4 patients; 3 were women; age 23-40 yearsTacrolimus (0.1%) ointment bid; 1 patient had combination treatment with doxycycline 100 mg/dNoneFD in remission at follow-up (range 2 mon-2.5 y); relapse occurred shortly after treatment discontinuedGrade 4
      11) Retrospective, case report [Parlette et al; Dermatol Surg. 2004;30(8): 1152-4]Dicloxacillin, tetralysal, doxycycline, minocycline, levofloxacin, ILT, IST, 1 course radiation26-year old manNd:YAG laser at 28 J/cm2, 3-msec pulse duration, a 12-mm spot, and dynamic cryogen spray cooling set at 50-msec spray and 20-msec delay; patient received 8 treatments at 4-wk to 6-wk intervalsSignificant pain during treatmentFD in remission at 6 mon follow-upGrade 4
      12) Retrospective, case report [Gemmeke et al; Acta Dermatovenerol Alp Pannonica Adriat. 2006; 15(4):184-186]Prednisolone, ampicillin27-year-old manIST 30 mg/d, oral clindamycin 300 mg/d for 6 wk, prednisolone 20 mg/d tapered within 3 wkNoneAt 3 wk, marked reduction in inflammation and partial regrowth in nonscarred scalp areas; at 6-mon follow-up, no disease progressionGrade 4
      13) Retrospective, case report [Kaur et al; J of Dermatol. 2002;29(7): 180-181]Multiple short courses of low-dose corticosteroids and antibiotics42-year-old manRifampicin 600 mg po 1x/d; topical 2% mupirocin ointmentNoneAt 2 wk, pain and folliculitis disappeared, and no new pustules formed; alopecia did not extend but scarring persisted; complete resolution of FD at 6-mon follow-upGrade 4
      14) Retrospective, case report [Kunte et al; J Am Acad Dermatol. 1998;39(5 Pt2): 891-3]Flucloxacillin, IST, topical superpotent CS27-year-old manDapsone 100 mg/dNoneFD in remission for 18 monGrade 4
      ACP, American College of Physicians; bid, 2 times a day; CS, corticosteroids; CsA, cyclosporin; FD, folliculitis decalvans; ILT, Intralesional triamcinolone; IST, Isotretinoin; IVIG, Intravenous immunoglobulin; MAL, methyl aminolevulinate; Nd:YAG, neodymium:yttrium aluminum garnet; PDT, photodynamic therapy; po, per oral.
      Overall, all studies evaluated had small sample sizes, lacked control groups, and randomization. In addition, given the retrospective nature of the included studies, blinding was not possible so observer bias might have occurred. Combination of clindamycin and rifampicin was the most commonly used treatment in reviewed studies. However, based on low quality of evidence, we are unable to discern whether it is the most efficacious treatment. The lack of higher grade evidence highlights the need for stronger studies performed to assess the efficacy of various treatments used for folliculitis decalvans, though the rarity of FD makes this challenging.

      Appendix

      Figure thumbnail fx1
      Supplemental Fig 1American College of Physicians treatment grading guidelines.
      • Qaseem A.
      • Snow V.
      • Owens D.K.
      • Shekelle P.
      The development of clinical practice guidelines and guidance statements of the American College of Physicians: summary of methods.

      References

        • Miguel-Gomez L.
        • Vano-galvan S.
        • Perez-garcia B.
        • Carrillo-gijon R.
        • Jaen-olasolo P.
        Treatment of folliculitis decalvans with photodynamic therapy: results in 10 patients.
        J Am Acad Dermatol. 2015; 72: 1085-1087
        • Qaseem A.
        • Snow V.
        • Owens D.K.
        • Shekelle P.
        The development of clinical practice guidelines and guidance statements of the American College of Physicians: summary of methods.
        Ann Intern Med. 2010; 153: 194-199
        • Vano-Galvan S.
        • Molina-Ruiz A.M.
        • Fernandez-Crehuet P.
        • et al.
        Folliculitis decalvans: a multicentre review of 82 patients.
        J Eur Acad Dermatol Venereol. 2015; 29: 1750-1757
        • Powell J.J.
        • Dawber R.P.
        • Gatter K.
        Folliculitis decalvans including tufted folliculitis: clinical, histological and therapeutic findings.
        Br J Dermatol. 1999; 140: 328-333
        • Miguel-Gomez L.
        • Rodrigues-Barata A.R.
        • Molina-Ruiz A.
        • et al.
        Folliculitis decalvans: effectiveness of therapies and prognostic factors in a multicenter series of 60 patients with long-term follow-up.
        J Am Acad Dermatol. 2018; https://doi.org/10.1016/j.jaad.2018.05.1240
        • Tietze J.K.
        • Heppt M.V.
        • von Preussen A.
        • et al.
        Oral isotretinoin as the most effective treatment in folliculitis decalvans: a retrospective comparison of different treatment regimens in 28 patients.
        J Eur Acad Dermatol Venereol. 2015; 29: 1816-1821
        • Bunagan M.J.K.
        • Banka N.
        • Shapiro J.
        Retrospective Review of folliculitis decalvans in 23 patients with course and treatment analysis of long-standing cases.
        J Cutan Med Surg. 2015; 19: 45-49
        • Aksoy B.
        • Hapa A.
        • Mutlu E.
        Isotretinoin treatment for folliculitis decalvans: a retrospective case-series study.
        Int J Dermatol. 2018; 57: 250-253