Treatment modalities for lymphocytic and neutrophilic scarring alopecia

Primary cicatricial alopecia can result in permanent hair loss from the destruction of hair follicles. Early intervention is key in controlling disease progression, reducing symptoms, and optimizing hair density. Treatment modalities range from topical and intralesional therapies to oral medications and light therapy. Primary cicatricial alopecia can result in permanent hair loss from the destruction of hair follicles. Early intervention is key in controlling disease progression, reducing symptoms, and optimizing hair density. Treatment modalities range from topical and intralesional therapies to oral medications and light therapy. Capsule Summary•Scarring alopecia consists of both lymphocytic and neutrophilic disorders. Early intervention is the key to management and focuses on reducing symptoms, slowing disease progression, and improving hair density.•Treatments differ slightly depending on the nature of the condition. Our article discusses the various treatments for lymphocytic and neutrophilic alopecia.CME Credit StatementThe American Academy of Dermatology is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American Academy of Dermatology designates this Journal-based CME activity for a maximum of 8 AMA PRA Category 1 Credits™.To claim CME credit for this activity, the learner must read all eight supplement articles, complete post-test with a passing score of 70% or higher, and complete the post-activity evaluation survey. The post-test and evaluation are available here: https://learning.aad.org/URL/JAADSUP2023Commercial SupportAll content solely developed by the American Academy of Dermatology.Publication of this supplement was supported in part by educational grants from Pfizer Inc. and Lilly USA, LLC. •Scarring alopecia consists of both lymphocytic and neutrophilic disorders. Early intervention is the key to management and focuses on reducing symptoms, slowing disease progression, and improving hair density.•Treatments differ slightly depending on the nature of the condition. Our article discusses the various treatments for lymphocytic and neutrophilic alopecia. CME Credit Statement The American Academy of Dermatology is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American Academy of Dermatology designates this Journal-based CME activity for a maximum of 8 AMA PRA Category 1 Credits™. To claim CME credit for this activity, the learner must read all eight supplement articles, complete post-test with a passing score of 70% or higher, and complete the post-activity evaluation survey. The post-test and evaluation are available here: https://learning.aad.org/URL/JAADSUP2023 Commercial Support All content solely developed by the American Academy of Dermatology. Publication of this supplement was supported in part by educational grants from Pfizer Inc. and Lilly USA, LLC. Primary cicatricial alopecia (PCA) refers to a group of disorders that result in permanent hair loss. Lymphocytic disorders largely consist of lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), and central centrifugal cicatricial alopecia (CCCA), whereas neutrophilic disorders encompass folliculitis decalvans and dissecting cellulitis. Given the permanent nature of PCA, early intervention is the key to the management of these disorders. Treatment is focused on reducing symptoms, slowing disease progression, and improving hair density in areas with functional hair follicles. In this article, we describe our specific approach to treating PCAs. We acknowledge that treatment ladders and frequency of application may differ depending on the provider. First-line treatments for mild lymphocytic PCA typically include topical and intralesional medications. Topical high-potency steroids should be used cautiously on the frontal hairline to prevent atrophy and should not be applied on the face. A series of intralesional scalp steroid injections every 4 to 6 weeks may be used as needed for more active cases. Compounded topical 10% metformin cream can promote hair regrowth and is thought to normalize the fibroproliferative process in the CCCA.1Araoye E.F. Thomas J.A.L. Aguh C.U. Hair regrowth in 2 patients with recalcitrant central centrifugal cicatricial alopecia after use of topical metformin.JAAD Case Rep. 2020; 6: 106-108Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar Topical calcineurin inhibitors, such as tacrolimus or pimecrolimus, can be applied 2 to 3 times per week or daily to the frontal hairline and eyebrows depending on patient preference. The use of calcineurin inhibitors can help avoid steroid side effects, such as telangiectasias, which makes assessing perifollicular erythema and response to therapy difficult.2Cummins D.M. Chaudhry I.H. Harries M. Scarring alopecias: pathology and an update on digital developments.Biomedicines. 2021; 9: 1755Crossref Scopus (2) Google Scholar It is postulated that a mix of environmental triggers and genetic susceptibility can lead to the development of FFA.3Tziotzios C. Petridis C. Dand N. et al.Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B∗07:02.Nat Commun. 2019; 10: 1150Crossref PubMed Scopus (69) Google Scholar An important first step in controlling scalp symptoms is to limit exposure to certain ingredients in personal care products.4Kwa M. Welty L.J. Xu S. Adverse events reported to the US Food and Drug Administration for cosmetics and personal care products.JAMA Intern Med. 2017; 177: 1202-1204Crossref PubMed Scopus (42) Google Scholar Several studies have reported an association between the use of facial skin care products, especially those containing chemical sunscreens, and FFA.5Aldoori N. Dobson K. Holden C.R. McDonagh A.J. Harries M. Messenger A.G. Frontal fibrosing alopecia: possible association with leave-on facial skin care products and sunscreens; a questionnaire study.Br J Dermatol. 2016; 175: 762-767Crossref PubMed Scopus (114) Google Scholar, 6Debroy Kidambi A. Dobson K. Holmes S. et al.Frontal fibrosing alopecia in men: an association with facial moisturizers and sunscreens.Br J Dermatol. 2017; 177: 260-261Crossref PubMed Scopus (62) Google Scholar, 7Thompson C.T. Chen Z.Q. Kolivras A. Tosti A. Identification of titanium dioxide on the hair shaft of patients with and without frontal fibrosing alopecia: a pilot study of 20 patients.Br J Dermatol. 2019; 181: 216-217Crossref PubMed Scopus (20) Google Scholar Two case-control studies showed that facial moisturizers and sunscreens were applied more frequently (at least twice a week) in patients with FFA compared with controls.5Aldoori N. Dobson K. Holden C.R. McDonagh A.J. Harries M. Messenger A.G. Frontal fibrosing alopecia: possible association with leave-on facial skin care products and sunscreens; a questionnaire study.Br J Dermatol. 2016; 175: 762-767Crossref PubMed Scopus (114) Google Scholar,6Debroy Kidambi A. Dobson K. Holmes S. et al.Frontal fibrosing alopecia in men: an association with facial moisturizers and sunscreens.Br J Dermatol. 2017; 177: 260-261Crossref PubMed Scopus (62) Google Scholar Titanium dioxide, which is a UV filter used in some sunscreens, has also been implicated in FFA.7Thompson C.T. Chen Z.Q. Kolivras A. Tosti A. Identification of titanium dioxide on the hair shaft of patients with and without frontal fibrosing alopecia: a pilot study of 20 patients.Br J Dermatol. 2019; 181: 216-217Crossref PubMed Scopus (20) Google Scholar As a precaution, we recommend that patients with FFA/LPP avoid daily use of chemical sunscreens and/or sunscreens containing titanium dioxide. Furthermore. general allergen avoidance is important in controlling scalp symptoms. A cohort study showed that 76% of patients with FFA and LPP tested positively for clinically relevant allergens in cosmetic and personal care products applied to the scalp and face. After 3 months of allergen avoidance, most patients reported improved symptoms.8Prasad S. Marks D.H. Burns L.J. et al.Patch testing and contact allergen avoidance in patients with lichen planopilaris and/or frontal fibrosing alopecia: a cohort study.J Am Acad Dermatol. 2020; 83: 659-661Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar Second-line treatments for lymphocytic PCA include hydroxychloroquine and phototherapy. Doxycycline, low-dose naltrexone, oral antihistamines, and oral gabapentin have also shown some efficacy in reducing symptoms of PCA, such as scalp pruritus.9Lajevardi V. Salarvand F. Ghiasi M. Nasimi M. Taraz M. The efficacy and safety of oral low dose naltrexone versus placebo in the patients with lichen planopilaris: a randomized controlled clinical trial.J Dermatolog Treat. 2022; 33: 769-773Crossref Scopus (4) Google Scholar, 10Klein E. Karim M. Kim R. Lo Sicco K. Shapiro J. Reversible hair loss in lichen planopilaris: regrowth with low-dose naltrexone and platelet-rich plasma.J Drugs Dermatol. 2022; 21: 671-673Crossref Scopus (2) Google Scholar, 11d’Ovidio R Rossi A. Di Prima T.M. Therapeutic hotline. Effectiveness of the association of cetirizine and topical steroids in lichen planus pilaris–an open-label clinical trial.Dermatol Ther. 2010; 23: 547-552Crossref Scopus (11) Google Scholar Hydroxychloroquine is a systemic immunomodulator used for the management of many rheumatologic and dermatologic conditions, including PCA.12Chiang C. Sah D. Cho B.K. Ochoa B.E. Price V.H. Hydroxychloroquine and lichen planopilaris: efficacy and introduction of Lichen Planopilaris Activity Index scoring system.J Am Acad Dermatol. 2010; 62: 387-392Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar,13Ochsendorf F.R. Use of antimalarials in dermatology.J Dtsch Dermatol Ges. 2010; 8: 829-844Google Scholar In patients with LPP and/or FFA, hydroxychloroquine was found to reduce scalp signs and symptoms as measured by the Lichen Planopilaris Activity Index by 69% and 83% after 6 and 12 months, respectively.12Chiang C. Sah D. Cho B.K. Ochoa B.E. Price V.H. Hydroxychloroquine and lichen planopilaris: efficacy and introduction of Lichen Planopilaris Activity Index scoring system.J Am Acad Dermatol. 2010; 62: 387-392Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar Optimal dosing was <5 mg/kg of actual body weight or <400 mg daily.14Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (453) Google Scholar The most critical risk factor for retinopathy is the daily dose, and this risk increases after 7 to 10 years of use. Therefore, a dilated eye examination is required within 3 months after starting the drug, and then annually thereafter. It is important to note that concurrent tamoxifen therapy (odds ratio, 2.08) and renal disease (odds ratio, 4.59) increase the risk of hydroxychloroquine-associated retinopathy.14Melles R.B. Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy.JAMA Ophthalmol. 2014; 132: 1453-1460Crossref PubMed Scopus (453) Google Scholar Mycophenolate mofetil is an alternative treatment to hydroxychloroquine,15Cho B.K. Sah D. Chwalek J. et al.Efficacy and safety of mycophenolate mofetil for lichen planopilaris.J Am Acad Dermatol. 2010; 62: 393-397Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar but has not been extensively studied in FFA or CCCA. Narrowband UV-B and excimer laser (308 nm) are effective in treating PCA,16Randolph M.J. Salhi W.A. Tosti A. Lichen planopilaris and low-level light therapy: four case reports and review of the literature about low-level light therapy and lichenoid dermatosis.Dermatol Ther (Heidelb). 2020; 10: 311-319Crossref Scopus (11) Google Scholar, 17Navarini A.A. Kolios A.G. Prinz-Vavricka B.M. Haug S. Trüeb R.M. Low-dose excimer 308-nm laser for treatment of lichen planopilaris.Arch Dermatol. 2011; 147: 1325-1326Crossref PubMed Scopus (31) Google Scholar, 18Pathoulas J.T. Flanagan K.E. Su M.Y. et al.A prospective pilot study of narrowband UV-B treatment of lichen planopilaris.J Am Acad Dermatol. 2022; 87: 703-705Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar and protocols for treatment are based on an individual patient’s Fitzpatrick Skin Type and are similar to those used for scalp psoriasis. A recent pilot study in 16 patients with LPP showed that monotherapy with a narrowband UV-B fiber-optic brush (300-320 nm) led to a significant reduction in scalp inflammation as measured by the target area scale and erythema at month 0 and 6. Furthermore, there was a significant reduction in the Lichen Planopilaris Activity Index scores.18Pathoulas J.T. Flanagan K.E. Su M.Y. et al.A prospective pilot study of narrowband UV-B treatment of lichen planopilaris.J Am Acad Dermatol. 2022; 87: 703-705Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Treatments for recalcitrant or severe lymphocytic PCA include mycophenolate mofetil,19Mostafa N. Phan K. Smith S. Mycophenolate mofetil and lichen planopilaris: systematic review and meta-analysis.J Dermatolog Treat. 2022; 33: 369-372Crossref Scopus (3) Google Scholar,20Azizpour A. Hatami P. Lajevardi V. Mohammadi M. Aryanian Z. Mohandesi N.A. Clinical efficacy of mychophenolate mofetil in treating lichen planopilaris.Dermatol Ther. 2022; 35: e15625Crossref Scopus (1) Google Scholar methotrexate,21Fatemi F. Esfahanian F. Asilian A. Mohaghegh F. Saber M. Comparative efficacy study combination of oral methotrexate and prednisolone versus oral methotrexate in patients with lichen planopilaris.Dermatol Res Pract. 2022; 2022: 3792489Crossref Scopus (2) Google Scholar cyclosporine,22Fatemi Naeini F. Mohaghegh F. Jelvan M. Asilian A. Saber M. Cyclosporine or methotrexate, which one is more promising in the treatment of lichen planopilaris? A comparative clinical trial.Int Immunopharmacol. 2020; 86: 106765Crossref PubMed Scopus (6) Google Scholar pioglitazone,23Karim M. Klein E.J. Brinster N. Rieder E. Lo Sicco K. Shapiro J. Reversible hair loss in a patient with cicatricial alopecia: a case of regrowth associated with pioglitazone use.JAAD Case Rep. 2022; 28: 21-23Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 24Lajevardi V. Ghiasi M. Balighi K. et al.Efficacy and safety of oral pioglitazone in the management of lichen planopilaris in comparison with clobetasol: a randomized clinical trial.Dermatol Ther. 2022; 35: e15868Crossref Scopus (2) Google Scholar, 25Peterson E.L. Gutierrez D. Brinster N.K. Lo Sicco K.I. Shapiro J. Response of lichen planopilaris to pioglitazone hydrochloride.J Drugs Dermatol. 2019; 18: 1276-1279PubMed Google Scholar dutasteride,26Pindado-Ortega C. Saceda-Corralo D. Moreno-Arrones Ó.M. et al.Effectiveness of dutasteride in a large series of patients with frontal fibrosing alopecia in real clinical practice.J Am Acad Dermatol. 2021; 84: 1285-1294Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar and topical or oral Janus kinase inhibitors.27Yang C.C. Khanna T. Sallee B. Christiano A.M. Bordone L.A. Tofacitinib for the treatment of lichen planopilaris: A case series.Dermatol Ther. 2018; 31: e12656Crossref PubMed Scopus (55) Google Scholar,28Plante J. Eason C. Snyder A. Elston D. Tofacitinib in the treatment of lichen planopilaris: A retrospective review.J Am Acad Dermatol. 2020; 83: 1487-1489Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar The choice of which agent to use depends on physician comfort and patient tolerability of potential side effects. Unfortunately, the treatment is often unsatisfactory. Finasteride and dutasteride led to improvement and stabilization of FFA in most patients,29Vañó-Galván S. Molina-Ruiz A.M. Serrano-Falcón C. et al.Frontal fibrosing alopecia: A multicenter review of 355 patients.J Am Acad Dermatol. 2014; 70: 670-678Abstract Full Text Full Text PDF PubMed Scopus (334) Google Scholar but has not been specifically studied for LPP or CCCA. A case series of 10 LPP/FFA patients on 10 to 15 mg of oral tofacitinib daily showed a significant reduction in Lichen Planopilaris Activity Index scores in 80% of patients.27Yang C.C. Khanna T. Sallee B. Christiano A.M. Bordone L.A. Tofacitinib for the treatment of lichen planopilaris: A case series.Dermatol Ther. 2018; 31: e12656Crossref PubMed Scopus (55) Google Scholar A retrospective review of 9 patients receiving topical tofacitinib 2% cream twice a day or 5 mg oral tofacitinib 2 to 3 times a day reported that all patients on oral tofacitinib improved.28Plante J. Eason C. Snyder A. Elston D. Tofacitinib in the treatment of lichen planopilaris: A retrospective review.J Am Acad Dermatol. 2020; 83: 1487-1489Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Three of 4 patients on topical tofacitinib showed improvement as well. Overall, Janus kinase inhibitors are well-tolerated, but potential side effects must be discussed with patients. In patients with concomitant female/male pattern hair loss, oral low-dose minoxidil at 0.625 to 1.25 mg daily and/or oral spironolactone at 12.5 to 100 mg daily is helpful in promoting hair growth and blocking androgens that trigger hair loss. For neutrophilic PCA, treatments aim to reduce inflammation and bacterial load. Benzoyl peroxide wash, topical steroids, steroid scalp injections, and oral doxycycline or minocycline 100 mg twice per day, and cephalexin 500 mg twice per day are first-line treatments for folliculitis decalvans. Rifampin 500 mg twice a day can be used in combination with clindamycin 500 mg twice a day for a more durable response.30Powell J.J. Dawber R.P. Gatter K. Folliculitis decalvans including tufted folliculitis: clinical, histological and therapeutic findings.Br J Dermatol. 1999; 140: 328-333Crossref Scopus (163) Google Scholar Oral prednisone and isotretinoin may be necessary for dissecting cellulitis. Systemic immunomodulators, such as dapsone, adalimumab, and infliximab, are reserved for patients with recalcitrant disease.