Abstract
While isotretinoin has been the gold-standard of therapy for severe acne since its approval in 1982, its anti-inflammatory properties makes it a potentially applicable and versatile therapy for a wide variety of dermatologic conditions yet to be explored. This systematic review comprehensively recounts the success of oral isotretinoin in non-acne cutaneous diseases and provide insight into future directions of isotretinoin utility. A systematic literature review was performed using PubMed. Search terms included “isotretinoin” OR “accutane” AND “skin” OR “dermatology” OR “hair” OR “nails” OR “rosacea” OR “psoriasis” OR “pityriasis rubra pilaris” OR “condyloma acuminata” OR “granuloma annulare” OR “darier’s disease” OR “non-melanoma skin cancer” OR “frontal fibrosing alopecia” OR “cutaneous lupus erythematosus” OR “hidradenitis suppurativa” OR “photodamaged skin” OR “skin aging” OR “wart” OR “flat warts” OR “plane warts” OR “lichen planus” OR “dissecting cellulitis” OR “folliculitis decalvans” OR “sebaceous hyperplasia” OR “cutaneous t-cell lymphoma” OR “mycosis fungoides.” A total of 169 studies discuss the use of oral isotretinoin for 16 non-acne dermatologic conditions, the most common being non-melanoma skin cancers (0.2–8.2 mg/kg/day), cutaneous T-cell lymphomas (0.5–2 mg/kg/day), and rosacea (0.22–1 mg/kg/day). Inflammatory conditions such as rosacea, granuloma annulare, and hidradenitis suppurativa benefit from lower oral isotretinoin dosage of 0.3–1 mg/kg/day, whereas, hyperkeratotic diseases such as psoriasis and pityriasis rubra pilaris, consistently respond better to higher dosages of up to 2–4 mg/kg/day for lesion clearance. Recurrence of disease following discontinuation of isotretinoin have been reported for rosacea, psoriasis, granuloma annulare, Darier’s disease, dissecting cellulitis, and non-melanoma skin cancers. Disease exacerbation was reported in some patients with hidradenitis suppurativa. Off-label isotretinoin is an effective treatment choice for dermatological conditions beyond acne. Further prospective, randomized human trials are needed to clarify when and how to prescribe off-label isotretinoin for maximum efficacy and safety.
Similar content being viewed by others
References
Layton A (2009) The use of isotretinoin in acne. Dermatoendocrinology 1(3):162–169
King K, Jones DH, Daltrey DC, Cunliffe WJ (1982) A double-blind study of the effects of 13-cis-retinoic acid on acne, sebum excretion rate and microbial population. Br J Dermatol 107(5):583–590
Wysowski DK, Swann J, Vega A (2002) Use of isotretinoin (Accutane) in the United States: rapid increase from 1992 through 2000. J Am Acad Dermatol 46(4):505–509
Chen J, White T, Juzba M, Chang E (2002) Oral isotretinoin: an analysis of its utilization in a managed care organization. J Manag Care Spec Pharm 8(4):272–277
Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC (1997) Current use and future potential role of retinoids in dermatology. Drugs 53(3):358–388
Layton AM, Dreno B, Gollnick HP, Zouboulis CC (2006) A review of the European Directive for prescribing systemic isotretinoin for acne vulgaris. J Eur Acad Dermatol Venereol 20(7):773–776
Strauss JS, Rapini RP, Shalita AR, Konecky E, Pochi PE, Comite H et al (1984) Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol 10(3):490–496
Bollag W (1972) Prophylaxis of chemically induced benign and malignant epithelial tumorsby vitamin A acid (retinoic acid). Eur J Cancer 8:689–693
Huen AO, Kim EJ (2015) The role of systemic retinoids in the treatment of cutaneous T cell lymphoma. Dermatol Clin 33(4):715–729
Boer J, van Gemert MJ (1999) Long-term results of isotretinoin in the treatment of 68 patients with hidradenitis suppurativa. J Am Acad Dermatol 40(1):73–76
Recchia F, De Filippis S, Rosselli M, Saggio G, Fumagalli L, Rea S (2002) Interleukin-2 and 13-cis retinoic acid in the treatment of minimal residual disease: a phase II study. Int J Oncol 20(6):1275–1282
Vollberg TM Sr, Nervi C, George MD, Fujimoto W, Krust A, Jetten AM (1992) Retinoic acid receptors as regulators of human epidermal keratinocyte differentiation. Mol Endocrinol 6(5):667–676
Group OLoEW (2011) The Oxford 2011 Levels of Evidence. [cited; Available from: https://www.cebm.net/index.aspx?o=5653
Bagheri MM, Safai B (2001) Cutaneous malignancies of keratinocytic origin. Clin Dermatol 19(3):244–252
Nickle SB, Peterson N, Peterson M (2014) Updated physician’s guide to the off-label uses of oral isotretinoin. J Clin Aesthet Dermatol 7(4):22–34
Goldberg LH, Hsu SH, Alcalay J (1989) Effectiveness of isotretinoin in preventing the appearance of basal cell carcinomas in basal cell nevus syndrome. J Am Acad Dermatol 21(1):144–145
Peck GL, Gross EG, Butkus D, DiGiovanna JJ (1982) Chemoprevention of basal cell carcinoma with isotretinoin. J Am Acad Dermatol. 6(4 Pt 2 Suppl):815–823
Peck GL, DiGiovanna JJ, Sarnoff DS, Gross EG, Butkus D, Olsen TG et al (1988) Treatment and prevention of basal cell carcinoma with oral isotretinoin. J Am Acad Dermatol 19(1 Pt 2):176–185
Sollitto RB, DiGiovanna JJ (1996) Failure of interferon alfa and isotretinoin combination therapy in the nevoid basal cell carcinoma syndrome. Arch Dermatol 132(1):94–95
Toma S, Palumbo R, Vincenti M, Aitini E, Paganini G, Pronzato P et al (1994) Efficacy of recombinant alpha-interferon 2a and 13-cis-retinoic acid in the treatment of squamous cell carcinoma. Ann Oncol 5(5):463–465
Lippman SM, Meyskens FL Jr (1987) Treatment of advanced squamous cell carcinoma of the skin with isotretinoin. Ann Intern Med 107(4):499–502
Lippman SM, Parkinson DR, Itri LM, Weber RS, Schantz SP, Ota DM et al (1992) 13-cis-retinoic acid and interferon alpha-2a: effective combination therapy for advanced squamous cell carcinoma of the skin. J Natl Cancer Inst 84(4):235–241
Meyskens FL Jr, Gilmartin E, Alberts DS, Levine NS, Brooks R, Salmon SE et al (1982) Activity of isotretinoin against squamous cell cancers and preneoplastic lesions. Cancer Treat Rep 66(6):1315–1319
Skroza N, Proietti I, Tolino E, Bernardini N, La Viola G, Nicolucci F et al (2014) Isotretinoin for the treatment of squamous cell carcinoma arising on an epidermoid cyst. Dermatol Ther 27(2):94–96
Bellman BA, Eaglstein WH, Miller J (1996) Low dose isotretinoin in the prophylaxis of skin cancer in renal transplant patients. Transplantation 61(1):173
Feldman RJ, Maize JC (2007) Multiple keratoacanthomas in a young woman: report of a case emphasizing medical management and a review of the spectrum of multiple keratoacanthomas. Int J Dermatol 46(1):77–79
Haydey RP, Reed ML, Dzubow LM, Shupack JL (1980) Treatment of keratoacanthomas with oral 13-cis-retinoic acid. N Engl J Med 303(10):560–562
Levine N, Miller RC, Meyskens FL Jr (1984) Oral isotretinoin therapy. Use in a patient with multiple cutaneous squamous cell carcinomas and keratoacanthomas. Arch Dermatol 120(9):1215–1217
Shaw JC, White CR Jr (1986) Treatment of multiple keratoacanthomas with oral isotretinoin. J Am Acad Dermatol 15(5 Pt 2):1079–1082
Schaller M, Korting HC, Wolff H, Schirren CG, Burgdorf W (1996) Multiple keratoacanthomas, giant keratoacanthoma and keratoacanthoma centrifugum marginatum: development in a single patient and treatment with oral isotretinoin. Acta Derm Venereol 76(1):40–42
Hong WK, Endicott J, Itri LM, Doos W, Batsakis JG, Bell R et al (1986) 13-cis-retinoic acid in the treatment of oral leukoplakia. N Engl J Med 315(24):1501–1505
Kraemer KH, DiGiovanna JJ, Moshell AN, Tarone RE, Peck GL (1988) Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med 318(25):1633–1637
Saade M, Debahy NE, Houjeily S (1999) Clinical remission of xeroderma pigmentosum-associated squamous cell carcinoma with isotretinoin and chemotherapy: case report. J Chemother 11(4):313–317
Zaman S, Gillani JA, Nabeela N, Khattak R, Iqbal I, Ul-Ain N et al (2014) Role of isotretinoin in cancer prevention and management in malignancies associated with xeroderma pigmentosum. J Ayub Med Coll Abbottabad 26(2):255–257
Moon TE, Levine N, Cartmel B, Bangert JL (1997) Retinoids in prevention of skin cancer. Cancer Lett 114(1–2):203–205
Levine N, Moon TE, Cartmel B, Bangert JL, Rodney S, Dong Q et al (1997) Trial of retinol and isotretinoin in skin cancer prevention: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomark Prev. 6(11):957–961
Kraemer KH, DiGiovanna JJ, Peck GL (1992) Chemoprevention of skin cancer in xeroderma pigmentosum. J Dermatol 19(11):715–718
Bagatin E, Guadanhim LR, Enokihara MM, Sanudo A, Talarico S, Miot HA et al (2014) Low-dose oral isotretinoin versus topical retinoic acid for photoaging: a randomized, comparative study. Int J Dermatol 53(1):114–122
Bagatin E, Parada MO, Miot HA, Hassun KM, Michalany N, Talarico S (2010) A randomized and controlled trial about the use of oral isotretinoin for photoaging. Int J Dermatol 49(2):207–214
Hernandez-Perez E, Khawaja HA, Alvarez TY (2000) Oral isotretinoin as part of the treatment of cutaneous aging. Dermatol Surg 26(7):649–652
Rabello-Fonseca RM, Azulay DR, Luiz RR, Mandarim-de-Lacerda CA, Cuzzi T, Manela-Azulay M (2009) Oral isotretinoin in photoaging: clinical and histopathological evidence of efficacy of an off-label indication. J Eur Acad Dermatol Venereol 23(2):115–123
Ianhez M, Pinto SA, Miot HA, Bagatin E (2019) A randomized, open, controlled trial of tretinoin 0.05% cream vs low-dose oral isotretinoin for the treatment of field cancerization. Int J Dermatol. 58(3):365–373
Bravo BS, Azulay DR, Luiz RR, Mandarim-De-Lacerda CA, Cuzzi T, Azulay MM (2015) Oral isotretinoin in photoaging: objective histological evidence of efficacy and durability. An Bras Dermatol 90(4):479–486
Sander CA, Pfeiffer C, Kligman AM, Plewig G (1997) Chemotherapy for disseminated actinic keratoses with 5-fluorouracil and isotretinoin. J Am Acad Dermatol 36(2 Pt 1):236–238
Kalil CL, Fachinello FZ, Lamb FM, Comunello LN (2008) Use of oral isotretinoin in photoaging therapy. Skinmed 7(1):10–14
Tangrea JA, Edwards BK, Taylor PR, Hartman AM, Peck GL, Salasche SJ et al (1992) Long-term therapy with low-dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. Isotretinoin-Basal Cell Carcinoma Study Group. J Natl Cancer Inst. 84(5):328–332
Duvic M, Lemak NA, Redman JR, Eifel PJ, Tucker SL, Cabanillas FF et al (1996) Combined modality therapy for cutaneous T cell lymphoma. J Am Acad Dermatol 34(6):1022–1029
Duvic M, Apisarnthanarax N, Cohen DS, Smith TL, Ha CS, Kurzrock R (2003) Analysis of long-term outcomes of combined modality therapy for cutaneous T cell lymphoma. J Am Acad Dermatol 49(1):35–49
Knobler RM, Trautinger F, Radaszkiewicz T, Kokoschka EM, Micksche M (1991) Treatment of cutaneous T cell lymphoma with a combination of low-dose interferon alfa-2b and retinoids. J Am Acad Dermatol 24(2 Pt 1):247–252
Amitay-Laish I, Reiter O, Prag-Naveh H, Kershenovich R, Hodak E (2019) Retinoic acid receptor agonist as monotherapy for early-stage mycosis fungoides: does it work? J Dermatolog Treat 30(3):258–263
Thomsen K (1995) Cutaneous T cell lymphoma and calcitriol and isotretinoin treatment. Lancet 345(8964):1583
Su IJ, Cheng AL, Tsai TF, Lay JD (1993) Retinoic acid-induced apoptosis and regression of a refractory Epstein-Barr virus-containing T cell lymphoma expressing multidrug-resistance phenotypes. Br J Haematol 85(4):826–828
Wantzin GL, Thomsen K (1985) A new cutaneous side effect of isotretinoin. J Am Acad Dermatol 13(4):665
Warrell RP Jr, Coonley CJ, Kempin SJ, Myskowski P, Safai B, Itri LM (1983) Isotretinoin in cutaneous T cell lymphoma. Lancet 2(8350):629
Neely SM, Mehlmauer M, Feinstein DI (1987) The effect of isotretinoin in six patients with cutaneous T cell lymphoma. Arch Intern Med 147(3):529–531
Molin L, Thomsen K, Volden G, Aronsson A, Hammar H, Hellbe L et al (1987) Oral retinoids in mycosis fungoides and Sezary syndrome: a comparison of isotretinoin and etretinate. A study from the Scandinavian Mycosis Fungoides Group. Acta Derm Venereol. 67(3):232–236
Thomsen K, Molin L, Volden G, Lange Wantzin G, Hellbe L (1984) 13-cis-retinoic acid effective in mycosis fungoides. A report from the Scandinavian Mycosis Fungoides Group. Acta Derm Venereol. 64(6):563–566
Kessler JF, Jones SE, Levine N, Lynch PJ, Booth AR, Meyskens FL Jr (1987) Isotretinoin and cutaneous helper T cell lymphoma (mycosis fungoides). Arch Dermatol 123(2):201–204
Thomsen K, Hammar H, Molin L, Volden G (1989) Retinoids plus PUVA (RePUVA) and PUVA in mycosis fungoides, plaque stage. A report from the Scandinavian Mycosis Fungoides Group. Acta Derm Venereol. 69(6):536–538
Fitzpatrick JE, Mellette JR (1986) Treatment of mycosis fungoides with isotretinoin. J Dermatol Surg Oncol 12(6):626–629
Leverkus M, Rose C, Brocker EB, Goebeler M (2005) Follicular cutaneous T cell lymphoma: beneficial effect of isotretinoin for persisting cysts and comedones. Br J Dermatol 152(1):193–194
Kessler JF, Meyskens FL Jr, Levine N, Lynch PJ, Jones SE (1983) Treatment of cutaneous T cell lymphoma (mycosis fungoides) with 13-cis-retinoic acid. Lancet 1(8338):1345–1347
Zhang C, Duvic M (2006) Treatment of cutaneous T cell lymphoma with retinoids. Dermatol Ther 19(5):264–271
Ertl GA, Levine N, Kligman AM (1994) A comparison of the efficacy of topical tretinoin and low-dose oral isotretinoin in rosacea. Arch Dermatol 130(3):319–324
Gollnick H, Blume-Peytavi U, Szabo EL, Meyer KG, Hauptmann P, Popp G et al (2010) Systemic isotretinoin in the treatment of rosacea—doxycycline- and placebo-controlled, randomized clinical study. J Dtsch Dermatol Ges 8(7):505–515
Sbidian E, Vicaut E, Chidiack H, Anselin E, Cribier B, Dreno B et al (2016) A Randomized-controlled trial of oral low-dose isotretinoin for difficult-to-treat papulopustular rosacea. J Invest Dermatol 136(6):1124–1129
Bostanci O, Borelli C, Schaller M (2010) Treatment of extrafacial rosacea with low-dose isotretinoin. Acta Derm Venereol 90(4):409–410
Debroy Kidambi A, Tiffin NJ, Ramsay HM (2016) Atypical rosacea in a male patient: case study. Dermatol Online J 22(2)
Marsden JR, Shuster S, Neugebauer M (1984) Response of rosacea to isotretinoin. Clin Exp Dermatol 9(5):484–488
Schmidt JB, Gebhart W, Raff M, Spona J (1984) 13-cis-Retinoic acid in rosacea. Clinical and laboratory findings. Acta Derm Venereol. 64(1):15–21
Turjanmaa K, Reunala T (1987) Isotretinoin treatment of rosacea. Acta Derm Venereol 67(1):89–91
Uslu M, Savk E, Karaman G, Sendur N (2012) Rosacea treatment with intermediate-dose isotretinoin: follow-up with erythema and sebum measurements. Acta Derm Venereol 92(1):73–77
Wee JS, Tan KB (2017) Phymatous rosacea presenting with leonine facies and clinical response to isotretinoin. Australas J Dermatol 58(1):72–73
Erdogan FG, Yurtsever P, Aksoy D, Eskioglu F (1998) Efficacy of low-dose isotretinoin in patients with treatment-resistant rosacea. Arch Dermatol 134(7):884–885
Hoting E, Paul E, Plewig G (1986) Treatment of rosacea with isotretinoin. Int J Dermatol 25(10):660–663
Rademaker M (2018) Very low-dose isotretinoin in mild to moderate papulopustular rosacea; a retrospective review of 52 patients. Australas J Dermatol 59(1):26–30
Kwon HH, Jung JY, Lee WY, Bae Y, Park GH (2019) Combined treatment of recalcitrant papulopustular rosacea involving pulsed dye laser and fractional microneedling radiofrequency with low-dose isotretinoin. J Cosmet Dermatol 19:105–111
McFalda WL, Roebuck HL (2011) Rational management of papulopustular rosacea with concomitant facial seborrheic dermatitis: a case report. J Clin Aesthet Dermatol 4(1):40–42
Marquis K, Christensen LC, Rajpara A (2017) Dissecting cellulitis of the scalp with excellent response to isotretinoin. Pediatr Dermatol 34(4):e210–e211
Badaoui A, Reygagne P, Cavelier-Balloy B, Pinquier L, Deschamps L, Crickx B et al (2016) Dissecting cellulitis of the scalp: a retrospective study of 51 patients and review of literature. Br J Dermatol 174(2):421–423
Lee CN, Chen W, Hsu CK, Weng TT, Lee JY, Yang CC (2018) Dissecting folliculitis (dissecting cellulitis) of the scalp: a 66-patient case series and proposal of classification. J Dtsch Dermatol Ges 16(10):1219–1226
Mundi JP, Marmon S, Fischer M, Kamino H, Patel R, Shapiro J (2012) Dissecting cellulitis of the scalp. Dermatol Online J 18(12):8
Mihic LL, Tomas D, Situm M, Krolo I, Sebetic K, Sjerobabski-Masnec I et al (2011) Perifolliculitis capitis abscedens et suffodiens in a caucasian: diagnostic and therapeutic challenge. Acta Dermatovenerol Croat 19(2):98–102
Scerri L, Williams HC, Allen BR (1996) Dissecting cellulitis of the scalp: response to isotretinoin. Br J Dermatol 134(6):1105–1108
Georgala S, Korfitis C, Ioannidou D, Alestas T, Kylafis G, Georgala C (2008) Dissecting cellulitis of the scalp treated with rifampicin and isotretinoin: case reports. Cutis 82(3):195–198
Hintze JM, Howard BE, Donald CB, Hayden RE (2016) Surgical management and reconstruction of Hoffman’s disease (dissecting cellulitis of the scalp). Case Rep Surg 2016:2123037
Khaled A, Zeglaoui F, Zoghlami A, Fazaa B, Kamoun MR (2007) Dissecting cellulitis of the scalp: response to isotretinoin. J Eur Acad Dermatol Venereol 21(10):1430–1431
Koca R, Altinyazar HC, Ozen OI, Tekin NS (2002) Dissecting cellulitis in a white male: response to isotretinoin. Int J Dermatol 41(8):509–513
Segurado-Miravalles G, Camacho-Martinez FM, Arias-Santiago S, Serrano-Falcon C, Serrano-Ortega S, Rodrigues-Barata R et al (2017) Epidemiology, clinical presentation and therapeutic approach in a multicentre series of dissecting cellulitis of the scalp. J Eur Acad Dermatol Venereol 31(4):e199–e200
Wollina U, Gemmeke A, Koch A (2012) Dissecting cellulitis of the scalp responding to intravenous tumor necrosis factor-alpha antagonist. J Clin Aesthet Dermatol 5(4):36–39
Bachynsky T, Antonyshyn OM, Ross JB (1992) Dissecting folliculitis of the scalp. A case report of combined treatment using tissue expansion, radical excision, and isotretinoin. J Dermatol Surg Oncol. 18(10):877–880
Stites PC, Boyd AS (2001) Dissecting cellulitis in a white male: a case report and review of the literature. Cutis 67(1):37–40
Ellis CN, Krach KJ (2001) Uses and complications of isotretinoin therapy. J Am Acad Dermatol 45(5):S150–S157
Schleicher SM, Milstein HJ (1985) Resolution of disseminated granuloma annulare following isotretinoin therapy. Cutis 36(2):147–148
Schleicher SM, Milstein HJ, Lim SJ, Stanton CD (1992) Resolution of disseminated granuloma annulare with isotretinoin. Int J Dermatol 31(5):371–372
Ratnavel RC, Norris PG (1995) Perforating granuloma annulare: response to treatment with isotretinoin. J Am Acad Dermatol 32(1):126–127
Tang WY, Chong LY, Lo KK (1996) Resolution of generalized granuloma annulare with isotretinoin therapy. Int J Dermatol 35(6):455–456
Young HS, Coulson IH (2000) Granuloma annulare following waxing induced pseudofolliculitis-resolution with isotretinoin. Clin Exp Dermatol 25(4):274–276
Erkek E, Karaduman A, Bukulmez G, Senturk N, Ozkaya O (2001) An unusual form of generalized granuloma annulare in a patient with insulin-dependent diabetes mellitus. Acta Derm Venereol. 81(1):48–50
Adams DC, Hogan DJ (2002) Improvement of chronic generalized granuloma annulare with isotretinoin. Arch Dermatol 138(11):1518–1519
Arroyo MP (2003) Generalized granuloma annulare. Dermatol Online J 9(4):13
Buendia-Eisman A, Ruiz-Villaverde R, Blasco-Melguizo J, Serrano-Ortega S (2003) Generalized annular granuloma: response to isotretinoin. Int J Dermatol 42(4):321–322
Pasmatzi E, Georgiou S, Monastirli A, Tsambaos D (2005) Temporary remission of disseminated granuloma annulare under oral isotretinoin therapy. Int J Dermatol 44(2):169–171
Sahin MT, Turel-Ermertcan A, Ozturkcan S, Turkdogan P (2006) Generalized granuloma annulare in a patient with type II diabetes mellitus: successful treatment with isotretinoin. J Eur Acad Dermatol Venereol 20(1):111–114
Baskan EB, Turan A, Tunali S (2007) A case of generalized granuloma annulare with myelodysplastic syndrome: successful treatment with systemic isotretinoin and topical pimecrolimus 1% cream combination. J Eur Acad Dermatol Venereol 21(5):693–695
Clayton BD, Jorizzo JL, Hitchcock MG, Fleischer AB, Williford PM, Feldman SR et al (1997) Adult pityriasis rubra pilaris: a 10-year case series. J Am Acad Dermatol 36(6 Pt 1):959–964
Borok M, Lowe NJ (1990) Pityriasis rubra pilaris. Further observations of systemic retinoid therapy. J Am Acad Dermatol 22(5 Pt 1):792–795
Dicken CH (1994) Treatment of classic pityriasis rubra pilaris. J Am Acad Dermatol 31(6):997–999
Marrouche N, Kurban M, Kibbi AG, Abbas O (2014) Pityriasis rubra pilaris: clinicopathological study of 32 cases from Lebanon. Int J Dermatol 53(4):434–439
Allison DS, El-Azhary RA, Calobrisi SD, Dicken CH (2002) Pityriasis rubra pilaris in children. J Am Acad Dermatol 47(3):386–389
Dicken CH (1987) Isotretinoin treatment of pityriasis rubra pilaris. J Am Acad Dermatol 16(2 Pt 1):297–301
Gilgor RS, Chiaramonti A, Goldsmith LA, Lazarus GS (1980) Evaluation of 13-cis retinoic acid in lamellar ichthyosis, pityriasis rubra pilaris and Darier’s disease. Cutis 25(4):380–381
Goldsmith LA, Weinrich AE, Shupack J (1982) Pityriasis rubra pilaris response to 13-cis-retinoic acid (isotretinoin). J Am Acad Dermatol. 6(4 Pt 2 Suppl):710–715
Peck GL, Yoder FW, Olsen TG, Pandya MD, Butkus D (1978) Treatment of Darier’s disease, lamellar ichthyosis, pityriasis rubra pilaris, cystic acne, and basal cell carcinoma with oral 13-cis-retinoic acid. Dermatologica 157(Suppl 1):11–12
Risch J, Ashton RE, Lowe NJ, Chalet M (1984) 13-cis-retinoic acid for dyskeratinizing diseases–clinicopathological responses. Clin Exp Dermatol 9(5):472–483
Sehgal VN, Srivastava G, Aggarwal AK, Sardana K, Jain M (2006) Efficacy of isotretinoin in pityriasis rubra pilaris: unapproved use. Int J Dermatol 45(10):1238–1240
Akyol M, Ozcelik S (2005) Non-acne dermatologic indications for systemic isotretinoin. Am J Clin Dermatol 6(3):175–184
Cardamakis E, Kotoulas IG, Relakis K, Metalinos K, Michopoulos J, Stathopoulos E et al (1995) Comparative study of systemic interferon alfa-2a plus isotretinoin versus isotretinoin in the treatment of recurrent condyloma acuminatum in men. Urology 45(5):857–860
Cardamakis EK, Kotoulas IG, Dimopoulos DP, Stathopoulos EN, Michopoulos JT, Tzingounis VA (1996) Comparative study of systemic interferon alfa-2a with oral isotretinoin and oral isotretinoin alone in the treatment of recurrent condylomata accuminata. Arch Gynecol Obstet 258(1):35–41
Georgala S, Katoulis AC, Georgala C, Bozi E, Mortakis A (2004) Oral isotretinoin in the treatment of recalcitrant condylomata acuminata of the cervix: a randomised placebo controlled trial. Sex Transm Infect 80(3):216–218
Olsen EA, Kelly FF, Vollmer RT, Buddin DA, Weck PK (1989) Comparative study of systemic interferon alfa-nl and isotretinoin in the treatment of resistant condylomata acuminata. J Am Acad Dermatol 20(6):1023–1030
Tsambaos D, Georgiou S, Monastirli A, Sakkis T, Sagriotis A, Goerz G (1997) Treatment of condylomata acuminata with oral isotretinoin. J Urol 158(5):1810–1812
Jha AK, Sonthalia S, Ganguly S (2018) Oral isotretinoin as an adjunctive treatment for recurrent genital warts. J Am Acad Dermatol 78(2):e35–e36
Pasmatzi E, Kapranos N, Monastirli A, Melachrinou M, Georgiou S, Tsambaos D (2012) Large benign condyloma acuminatum: successful treatment with isotretinoin and interferon alpha. Acta Derm Venereol 92(3):249–250
Yew YW, Pan JY (2014) Complete remission of recalcitrant genital warts with a combination approach of surgical debulking and oral isotretinoin in a patient with systemic lupus erythematosus. Dermatol Ther. 27(2):79–82
Yildirim M, Inaloz HS, Baysal V, Kesici D, Candir O (2004) A case of condyloma acuminatum treated successfully with low-dose isotretinoin and interferon. Int J Clin Pract 58(9):889–891
Patel N, McKenzie SA, Harview CL, Truong AK, Shi VY, Chen L et al (2019) Isotretinoin in the treatment of hidradenitis suppurativa: a retrospective study. J Dermatolog Treat 26:1–3
Huang CM, Kirchhof MG (2017) A new perspective on isotretinoin treatment of hidradenitis suppurativa: a retrospective chart review of patient outcomes. Dermatology 233(2–3):120–125
Soria A, Canoui-Poitrine F, Wolkenstein P, Poli F, Gabison G, Pouget F et al (2009) Absence of efficacy of oral isotretinoin in hidradenitis suppurativa: a retrospective study based on patients’ outcome assessment. Dermatology 218(2):134–135
Dicken CH, Powell ST, Spear KL (1984) Evaluation of isotretinoin treatment of hidradenitis suppurativa. J Am Acad Dermatol 11(3):500–502
Jones DH, Cunliffe WJ, King K (1982) Hidradenitis suppurativa-lack of success with 13-cis-retinoic acid. Br J Dermatol 107(2):252
Norris JF, Cunliffe WJ (1986) Failure of treatment of familial widespread hidradenitis suppurativa with isotretinoin. Clin Exp Dermatol 11(6):579–583
Ornelas J, Sivamani R, Awasthi S (2016) A report of two patients with darier disease and hidradenitis suppurativa. Pediatr Dermatol 33(4):e265–e266
Jorgensen AR, Thomsen SF, Ring HC (2019) Isotretinoin and hidradenitis suppurativa. Clin Exp Dermatol 44(4):e155–e156
Burton CS, Sawchuk WS (1985) Premature sebaceous gland hyperplasia: successful treatment with isotretinoin. J Am Acad Dermatol 12(1 Pt 2):182–184
Grimalt R, Ferrando J, Mascaro JM (1997) Premature familial sebaceous hyperplasia: successful response to oral isotretinoin in three patients. J Am Acad Dermatol 37(6):996–998
Gupta V, Mridha AR, Sharma VK (2016) Sebaceous hyperplasia and sebaceous adenomas presenting as leonine facies and improving with oral isotretinoin. Clin Exp Dermatol 41(8):923–924
Jung HY, Kim M, Cho BK, Park HJ (2016) A case of cyclosporine-induced sebaceous hyperplasia in a renal transplant patient successfully treated with isotretinoin. Ann Dermatol 28(2):271–272
Liu YS, Cheng YP, Liu CI, Yang CY, Yang CY (2016) Presenile diffuse familial sebaceous hyperplasia successfully treated with low-dose isotretinoin: a report of two cases and review of the published work. J Dermatol 43(10):1205–1208
McDonald SK, Goh MS, Chong AH (2011) Successful treatment of cyclosporine-induced sebaceous hyperplasia with oral isotretinoin in two renal transplant recipients. Australas J Dermatol 52(3):227–230
Noh S, Shin JU, Jung JY, Lee JH (2014) A case of sebaceous hyperplasia maintained on low-dose isotretinoin after carbon dioxide laser treatment. Int J Dermatol 53(2):e151–e153
Tagliolatto S, Santos Neto-Ode O, Alchorne MM, Enokihara MY (2015) Sebaceous hyperplasia: systemic treatment with isotretinoin. An Bras Dermatol. 90(2):211–215
Wang W, Qiu Y, Zhou G, Pei Z, Zhang F (2016) Premature sebaceous hyperplasia with satisfactory response to oral isotretinoin. Indian J Dermatol Venereol Leprol. 82(1):113
Sehgal VN, Srivastava G (2005) Darier’s (Darier-White) disease/keratosis follicularis. Int J Dermatol 44(3):184–192
Takagi A, Kamijo M, Ikeda S (2016) Darier disease. J Dermatol 43(3):275–279
Del Rosso JQ, Horowitz DC (1986) Treatment of Darier’s disease with isotretinoin: report of a case. J Am Osteopath Assoc 86(10):634–638
Kim C, Fangman W (2007) Keratosis follicularis (Darier-White disease), with an unusual palmoplantar keratoderma. Dermatol Online J 13(1):7
Udayashankar C, Nath AK, Anuradha P (2013) Extensive Darier’s disease with pityriasis amiantacea, alopecia and congenital facial nerve palsy. Dermatol Online J 19(6):18574
Rotunda AM, Cotliar J, Haley JC, Craft N (2005) Unilateral Darier’s disease associated with migraine headache responsive to isotretinoin. J Am Acad Dermatol 52(1):175–176
Dicken CH, Bauer EA, Hazen PG, Krueger GG, Marks JG Jr, McGuire JS et al (1982) Isotretinoin treatment of Darier’s disease. J Am Acad Dermatol. 6(4 Pt 2 Suppl):721–726
Gahalaut P, Soodan PS, Mishra N, Rastogi MK, Soodan HS, Chauhan S (2014) Clinical efficacy of psoralen + sunlight vs combination of isotretinoin and psoralen + sunlight for the treatment of chronic plaque-type psoriasis vulgaris: a randomized hospital-based study. Photodermatol Photoimmunol Photomed. 30(6):294–301
Mortazavi H, Khezri S, Hosseini H, Khezri F, Vasigh M (2011) A single blind randomized clinical study: the efficacy of isotretinoin plus narrow band ultraviolet B in the treatment of psoriasis vulgaris. Photodermatol Photoimmunol Photomed 27(3):159–161
Al-Shobaili H, Al-Khenaizan S (2007) Childhood generalized pustular psoriasis: successful treatment with isotretinoin. Pediatr Dermatol. 24(5):563–564
Anstey A, Hawk JL (1997) Isotretinoin-PUVA in women with psoriasis. Br J Dermatol 136(5):798–799
Honigsmann H, Wolff K (1983) Isotretinoin-PUVA for psoriasis. Lancet 1(8318):236
Sofen HL, Moy RL, Lowe NJ (1984) Treatment of generalised pustular psoriasis with isotretinoin. Lancet 1(8367):40
Wilken R, Sharma A, Patel F, Maverakis E (2015) Successful treatment of palmoplantar pustulosis with isotretinoin. Dermatol Online J 21(8)
Moy RL, Kingston TP, Lowe NJ (1985) Isotretinoin vs etretinate therapy in generalized pustular and chronic psoriasis. Arch Dermatol 121(10):1297–1301
Okon L, Werth V (2013) Cutaneous lupus erythematosus: diagnosis and treatment. Best Pract Res Clin Rheumatol 27(3):391–404
Furner BB (1990) Subacute cutaneous lupus erythematosus response to isotretinoin. Int J Dermatol 29(8):587–590
Fabbri P, Cardinali C, Giomi B, Caproni M (2003) Cutaneous lupus erythematosus: diagnosis and management. Am J Clin Dermatol 4(7):449–465
Newton RC, Jorizzo JL, Solomon AR Jr, Sanchez RL, Daniels JC, Bell JD et al (1986) Mechanism-oriented assessment of isotretinoin in chronic or subacute cutaneous lupus erythematosus. Arch Dermatol 122(2):170–176
Rubenstein DJ, Huntley AC (1986) Keratotic lupus erythematosus: treatment with isotretinoin. J Am Acad Dermatol 14(5 Pt 2):910–914
Green SG, Piette WW (1987) Successful treatment of hypertrophic lupus erythematosus with isotretinoin. J Am Acad Dermatol 17(2 Pt 2):364–368
Shornick JK, Formica N, Parke AL (1991) Isotretinoin for refractory lupus erythematosus. J Am Acad Dermatol 24(1):49–52
Richardson TT, Cohen PR (2000) Subacute cutaneous lupus erythematosus: report of a patient who subsequently developed a meningioma and whose skin lesions were treated with isotretinoin. Cutis 66(3):183–188
D’Erme AM, Milanesi N, Difonzo EM, Lotti T, Gola M (2012) Treatment of refractory subacute cutaneous lupus erythematosus with oral isotretinoin: a valid therapeutic option. Dermatol Ther 25(3):281–282
Olguin-Garcia MG, Jurado-Santa Cruz F, Peralta-Pedrero ML, Morales-Sanchez MA (2015) A double-blind, randomized, placebo-controlled trial of oral isotretinoin in the treatment of recalcitrant facial flat warts. J Dermatolog Treat 26(1):78–82
Kaur GJ, Brar BK, Kumar S, Brar SK, Singh B (2017) Evaluation of the efficacy and safety of oral isotretinoin versus topical isotretinoin in the treatment of plane warts: a randomized open trial. Int J Dermatol 56(12):1352–1358
Al-Hamamy HR, Salman HA, Abdulsattar NA (2012) Treatment of plane warts with a low-dose oral isotretinoin. ISRN Dermatol 2012:163929
Miljkovic J (2012) A novel therapeutic approach to plane warts: a report on two cases. Acta Dermatovenerol Alp Pannonica Adriat 21(3):63–64
Bialecka A, Mecinska-Jundzill K, Adamska U, Cichewicz A, Bialecki M, Drewa G et al (2018) Plane warts on the back of the hand successfully treated with oral isotretinoin. Postepy Dermatol Alergol 35(2):227–229
Dave DD, Abdelmaksoud A (2019) Low dose isotretinoin as an adjuvant therapy for treatment of different clinical variants of warts: a case series. Dermatol Ther 32(2):e12836
Tietze JK, Heppt MV, von Preussen A, Wolf U, Ruzicka T, Wolff H et al (2015) 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 29(9):1816–1821
Aksoy B, Hapa A, Mutlu E (2018) Isotretinoin treatment for folliculitis decalvans: a retrospective case-series study. Int J Dermatol 57(2):250–253
Bunagan MJ, Banka N, Shapiro J (2015) Retrospective review of folliculitis decalvans in 23 patients with course and treatment analysis of long-standing cases. J Cutan Med Surg. 19(1):45–49
Miguel-Gomez L, Rodrigues-Barata AR, Molina-Ruiz A, Martorell-Calatayud A, Fernandez-Crehuet P, Grimalt R et al (2018) Folliculitis decalvans: effectiveness of therapies and prognostic factors in a multicenter series of 60 patients with long-term follow-up. J Am Acad Dermatol 79(5):878–883
Shireen F, Sudhakar A (2018) A case of isotretinoin therapy-refractory folliculitis decalvans treated successfully with biosimilar adalimumab (exemptia). Int J Trichol 10(5):240–241
Gemmeke A, Wollina U (2006) Folliculitis decalvans of the scalp: response to triple therapy with isotretinoin, clindamycin, and prednisolone. Acta Dermatovenerol Alp Pannonica Adriat 15(4):184–186
Babahosseini H, Tavakolpour S, Mahmoudi H, Balighi K, Teimourpour A, Ghodsi SZ et al (2019) Lichen planopilaris: retrospective study on the characteristics and treatment of 291 patients. J Dermatolog Treat 30(6):598–604
Mardones F, Shapiro J (2017) Lichen planopilaris in a Latin American (Chilean) population: demographics, clinical profile and treatment experience. Clin Exp Dermatol 42(7):755–759
Rakowska A, Gradzinska A, Olszewska M, Rudnicka L (2017) Efficacy of isotretinoin and acitretin in treatment of frontal fibrosing alopecia: retrospective analysis of 54 cases. J Drugs Dermatol 16(10):988–992
Pham CT, Hosking AM, Cox S, Mesinkovska NA (2020) Therapeutic response of facial papules and inflammation in frontal fibrosing alopecia to low-dose oral isotretinoin. JAAD Case Rep 6(5):453–456
Pedrosa AF, Duarte AF, Haneke E, Correia O (2017) Yellow facial papules associated with frontal fibrosing alopecia: a distinct histologic pattern and response to isotretinoin. J Am Acad Dermatol 77(4):764–766
Pirmez R, Duque-Estrada B, Barreto T, Quintella DC, Cuzzi T (2017) Successful treatment of facial papules in frontal fibrosing alopecia with oral isotretinoin. Skin Appendage Disord 3(2):111–113
Namazi N, Niknezhad N, Niknejad N, Asadi-Kani Z (2018) Familial facial lichen planopilaris and satisfactory response to isotretinoin. Dermatol Ther 31(5):e12633
Muthu SK, Narang T, Saikia UN, Kanwar AJ, Parsad D, Dogra S (2016) Low-dose oral isotretinoin therapy in lichen planus pigmentosus: an open-label non-randomized prospective pilot study. Int J Dermatol 55(9):1048–1054
Handler HL (1984) Isotretinoin for oral lichen planus. J Am Acad Dermatol 10(4):674
Camisa C, Allen CM (1986) Treatment of oral erosive lichen planus with systemic isotretinoin. Oral Surg Oral Med Oral Pathol 62(4):393–396
Boyd AS, King LE (2001) Lichenoid drug reaction from isotretinoin therapy. Cutis 68(4):301–303
Woo TY (1985) Systemic isotretinoin treatment of oral and cutaneous lichen planus. Cutis 35(4):385–386 (90–1, 93)
Rigopoulos D, Larios G, Katsambas AD (2010) The role of isotretinoin in acne therapy: why not as first-line therapy? Facts and controversies. Clin Dermatol. 28(1):24–30
Administration UFaD (2005) iPLEDGE program. Available from: http://www.ipledgeprogram.com/
Lamberg L (1998) Acne drug depression warnings highlight need for expert care. JAMA 279(14):1057
Funding
The authors did not receive funding for this research.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors do not have any conflicts of interest to disclose.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Chu, S., Michelle, L., Ekelem, C. et al. Oral isotretinoin for the treatment of dermatologic conditions other than acne: a systematic review and discussion of future directions. Arch Dermatol Res 313, 391–430 (2021). https://doi.org/10.1007/s00403-020-02152-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-020-02152-4