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Therapeutic Considerations for Severe Nodular Acne

  • Therapy In Practice
  • Therapy for Severe Nodular Acne
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Severe nodular acne, defined as grade 4 or 5 acne on the Investigator’s Static Global Assessment scale, is a skin condition characterized by intense erythema, inflammation, nodules, cysts, and scarring. Both the well known risk of physical scarring and the more recent recognition that acne can be a chronic, psychologically distressing disease with significant adverse effects on a patient’s quality of life, have prompted earlier, more aggressive treatment with more effective medications, in the hope of preventing progression to more severe, nodular forms of the disease. Oral antibacterials, primarily tetracyclines, have long been the first-line therapy for severe nodular acne, which frequently remained refractory to therapy. However, concerns of antibacterial adverse effects, patient adherence, and antimicrobial resistance prompted the search for alternate therapies and combinations thereof in order to target the multifactorial pathogenesis of the disease. Isotretinoin, an oral retinoid introduced in 1982, has since become the gold standard therapy in severe acne and has revolutionized its treatment. Several adjunctive agents exist. Oral antibacterials are indicated as an alternative for patients with severe acne who cannot tolerate oral retinoids, or for whom a contraindication exists. In order to prevent bacterial resistance, antibacterials should always be used in combination with benzoyl peroxide, a nonantibiotic antimicrobial agent with anti-inflammatory activity. Topical retinoids are often added to this regimen.

In women, hormonal agents, which include oral contraceptives, spironolactone, and oral corticosteroids, and, in Europe, cyproterone acetate, may be used as monotherapy or concomitantly with isotretinoin. For rapid treatment of inflammatory nodules, intralesional corticosteroids are effective.

These treatment modalities have been studied, refined, and combined in novel ways in order to target the multifactorial pathogenesis of the disease, and in this article we review each of their roles.

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References

  1. Shalita AR. Acne: clinical presentations. Clin Dermatol 2004 Sep-Oct; 22 (5): 385–6

    PubMed  Google Scholar 

  2. Shalita AR, Myers JA, Krochmal L, et al. The safety and efficacy of clindamycin phosphate foam 1% versus clindamycin phosphate topical gel 1% for the treatment of acne vulgaris. J Drugs Dermatol 2005 Jan-Feb; 4 (1): 48–56

  3. Bolognia J, Jorizzo J, Rapini R, editors. Dermatology. Philadelphia (PA): Mosby; 2003

  4. Pochi PE, Shalita AR, Strauss JS, et al. Report of the consensus conference on acne classification: Washington, DC, March 24 and 25, 1990. J Am Acad Dermatol 1991 Mar; 24 (3): 495–500

    PubMed  CAS  Google Scholar 

  5. Bolognia JL, Jorizzo JL, Rapini RP, editors. Dermatology. 2nd ed. Philadelphia (PA): Mosby Elsevier, 2008

  6. Farber EM, Claiborne ER. Acne conglobata; use of cortisone and corticotropin in therapy. Calif Med 1954 Aug; 81 (2): 76–8

    PubMed  PubMed Central  CAS  Google Scholar 

  7. Seukeran DC, Cunliffe WJ. The treatment of acne fulminans: a review of 25 cases. Br J Dermatol 1999 Aug; 141 (2): 307–9

    PubMed  CAS  Google Scholar 

  8. Jansen T, Plewig G, Kligman AM. Diagnosis and treatment of rosacea fulminans. Dermatology 1994; 188 (4): 251–4

    PubMed  CAS  Google Scholar 

  9. Gollnick H, Cunliffe W, Berson D, et al. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol 2003 Jul; 49 (1 Suppl.): S1–37

    PubMed  Google Scholar 

  10. Haider A, Shaw JC. Treatment of acne vulgaris. JAMA 2004 Aug 11; 292 (6): 726–35

    PubMed  CAS  Google Scholar 

  11. Thiboutot D, Gollnick H, Bettoli V, et al., Global Alliance to Improve Outcomes in Acne. New insights into themanagement of acne: an update from the Global Alliance to Improve Outcomes in Acne group. J Am Acad Dermatol 2009 May; 60 (5 Suppl.): S1–50

    PubMed  Google Scholar 

  12. Oberemok SS, Shalita AR. Acne vulgaris: I. Pathogenesis and diagnosis. Cutis 2002 Aug; 70 (2): 101–5

  13. Layton AM, Seukeran D, Cunliffe WJ. Scarred for life? Dermatology 1997; 195 Suppl. 1: 15–21; discussion 38-40

    PubMed  Google Scholar 

  14. Holland DB, Jeremy AH, Roberts SG, et al. Inflammation in acne scarring: a comparison of the responses in lesions from patients prone and not prone to scar. Br J Dermatol 2004 Jan; 150 (1): 72–81

    PubMed  CAS  Google Scholar 

  15. Eady EA. Bacterial resistance in acne. Dermatology 1998; 196 (1): 59–66

    PubMed  CAS  Google Scholar 

  16. Katsambas A, Papakonstantinou A. Acne: systemic treatment. Clin Dermatol 2004 Sep-Oct; 22 (5): 412–8

    PubMed  Google Scholar 

  17. Dréno B, Bettoli V, Ochsendorf F, et al. An expert view on the treatment of acne with systemic antibiotics and/or oral isotretinoin in the light of the new European recommendations. Eur J Dermatol 2006 Sep-Oct; 16 (5): 565–71

    PubMed  Google Scholar 

  18. Shalita A. The integral role of topical and oral retinoids in the early treatment of acne. J Eur Acad Dermatol Venereol 2001; 15 Suppl. 3: 43–9

    PubMed  Google Scholar 

  19. Leyden JJ. The role of isotretinoin in the treatment of acne: personal observations. J Am Acad Dermatol 1998 Aug; 39 (2 Pt 3): S45–9

    PubMed  CAS  Google Scholar 

  20. Goulden V, Layton AM, Cunliffe WJ. Current indications for isotretinoin as a treatment for acne vulgaris. Dermatology 1995; 190 (4): 284–7

    PubMed  CAS  Google Scholar 

  21. Wysowski DK, Swann J, Vega A. Use of isotretinoin (Accutane) in the United States: rapid increase from 1992 through 2000. J Am Acad Dermatol 2002 Apr; 46 (4): 505–9

    PubMed  Google Scholar 

  22. Layton AM, Knaggs H, Taylor J, et al. Isotretinoin for acne vulgaris: 10 years later: a safe and successful treatment. Br J Dermatol 1993 Sep; 129 (3): 292–6

    PubMed  CAS  Google Scholar 

  23. Shalita AR, Cunningham WJ, Leyden JJ, et al. Isotretinoin treatment of acne and related disorders: an update. J AmAcad Dermatol 1983 Oct; 9 (4): 629–38

    CAS  Google Scholar 

  24. Cunliffe WJ, van de Kerkhof PC, Caputo R, et al. Roaccutane treatment guidelines: results of an international survey. Dermatology 1997; 194 (4): 351–7

    PubMed  CAS  Google Scholar 

  25. Dhir R, Gehi NP, Agarwal R, et al. Oral isotretinoin is as effective as a combination of oral isotretinoin and topical anti-acne agents in nodulocystic acne. Indian J Dermatol Venereol Leprol 2008 Mar-Apr; 74 (2): 187

    PubMed  Google Scholar 

  26. Alestas T, Ganceviciene R, Fimmel S, et al. Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands. J Mol Med 2006 Jan; 84 (1): 75–87

    PubMed  CAS  Google Scholar 

  27. Demircay Z, Kus S, Sur H. Predictive factors for acne flare during isotretinoin treatment. Eur J Dermatol 2008 Jul-Aug; 18 (4): 452–6

  28. Layton AM, Cunliffe WJ. Guidelines for optimal use of isotretinoin in acne. J Am Acad Dermatol 1992 Dec; 27 (6 Pt 2): S2–7

    PubMed  CAS  Google Scholar 

  29. Stainforth JM, Layton AM, Taylor JP, et al. Isotretinoin for the treatment of acne vulgaris: which factors may predict the need for more than one course? Br J Dermatol 1993 Sep; 129 (3): 297–301

    PubMed  CAS  Google Scholar 

  30. Goulden V, Layton AM, Cunliffe WJ. Long-term safety of isotretinoin as a treatment for acne vulgaris. Br J Dermatol 1994 Sep; 131 (3): 360–3

    PubMed  CAS  Google Scholar 

  31. McLane J. Analysis of common side effects of isotretinoin. J Am Acad Dermatol 2001 Nov; 45 (5): S188–94

    PubMed  CAS  Google Scholar 

  32. Halpagi P, Grigg J, Klistorner A, et al. Night blindness following low-dose isotretinoin. J Eur Acad Dermatol Venereol 2008 Jul; 22 (7): 893–4

    PubMed  CAS  Google Scholar 

  33. Ellies P, Dighiero P, Legeais JM, et al. Persistent corneal opacity after oral isotretinoin therapy for acne. Cornea 2000 Mar; 19 (2): 238–9

    PubMed  CAS  Google Scholar 

  34. Gerber LH, Helfgott RK, Gross EG, et al. Vertebral abnormalities associated with synthetic retinoid use. J AmAcad Dermatol 1984 May; 10 (5 Pt 1): 817–23

    CAS  Google Scholar 

  35. Kilcoyne RF, Cope R, Cunningham W, et al. Minimal spinal hyperostosis with low-dose isotretinoin therapy. Invest Radiol 1986 Jan; 21 (1): 41–4

    PubMed  CAS  Google Scholar 

  36. Griffin JP. A review of the literature on benign intracranial hypertension associated with medication. Adverse Drug React Toxicol Rev 1992; 11 (1): 41–57

    PubMed  CAS  Google Scholar 

  37. Jick SS, Kremers HM, Vasilakis-Scaramozza C. Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Arch Dermatol 2000 Oct; 136 (10): 1231–6

    PubMed  CAS  Google Scholar 

  38. Marqueling AL, Zane LT. Depression and suicidal behavior in acne patients treated with isotretinoin: a systematic review. Semin Cutan Med Surg 2005 Jun; 24 (2): 92–102

    PubMed  CAS  Google Scholar 

  39. Schaefer C, Meister R, Weber-Schoendorfer C. Isotretinoin exposure and pregnancy outcome: an observational study of the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy. Arch Gynecol Obstet 2010 Feb; 281 (2): 221–7

    PubMed  Google Scholar 

  40. Cheetham TC, Wagner RA, Chiu G, et al. A risk management program aimed at preventing fetal exposure to isotretinoin: retrospective cohort study. J Am Acad Dermatol 2006 Sep; 55 (3): 442–8

    PubMed  Google Scholar 

  41. Weinberg JM. iPLEDGE allegiance. Cutis 2005 Dec; 76 (6): 356

  42. Dai WS, Hsu MA, Itri LM. Safety of pregnancy after discontinuation of isotretinoin. Arch Dermatol 1989 Mar; 125 (3): 362–5

    PubMed  CAS  Google Scholar 

  43. Mitchell AA, Van Bennekom CM, Louik C. A pregnancy-prevention program in women of childbearing age receiving isotretinoin. N Engl J Med 1995 Jul 13; 333 (2): 101–6

    CAS  Google Scholar 

  44. Hendrix CW, Jackson KA, Whitmore E, et al. The effect of isotretinoin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone. Clin Pharmacol Ther 2004 May; 75 (5): 464–75

    PubMed  CAS  Google Scholar 

  45. Altman RS, Altman LJ, Altman JS. A proposed set of new guidelines for routine blood tests during isotretinoin therapy for acne vulgaris. Dermatology 2002; 204 (3): 232–5

    PubMed  CAS  Google Scholar 

  46. Baxter KF, Ling TC, Barth JH, et al. Retrospective survey of serum lipids in patients receiving more than three courses of isotretinoin. J Dermatolog Treat 2003 Dec; 14 (4): 216–8

    PubMed  CAS  Google Scholar 

  47. Tan HH. Antibacterial therapy for acne: a guide to selection and use of systemic agents. Am J Clin Dermatol 2003; 4 (5): 307–14

    PubMed  Google Scholar 

  48. Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for acne vulgaris management. J Am Acad Dermatol 2007 Apr; 56 (4): 651–63

    PubMed  Google Scholar 

  49. Garner SE, Eady EA, Popescu C, et al. Minocycline for acne vulgaris: efficacy and safety. Cochrane Database Syst Rev 2003; (1): CD002086

  50. Garner SE, Eady EA, Popescu C, et al. Minocycline for acne vulgaris: efficacy and safety. Cochrane Database Syst Rev 2000; (2): CD002086

  51. Stewart DM, Torok HM, Weiss JS, et al. Dose-ranging efficacy of newonce-daily extended-release minocycline for acne vulgaris. Cutis 2006 Oct; 78 (4 Suppl.): 11–20

  52. Plott RT, Wortzman MS. Key bioavailability features of a new extendedrelease formulation of minocycline hydrochloride tablets. Cutis 2006 Oct; 78 (4 Suppl.): 6–10

  53. Hubbell CG, Hobbs ER, Rist T, et al. Efficacy of minocycline compared with tetracycline in treatment of acne vulgaris. Arch Dermatol 1982 Dec; 118 (12): 989–92

    PubMed  CAS  Google Scholar 

  54. Fleischer Jr AB, Dinehart S, Stough D, et al. Safety and efficacy of a new extended-release formulation of minocycline. Cutis 2006 Oct; 78 (4 Suppl.): 21–31

  55. Extended-release minocycline (Solodyn) for acne. Med Lett Drugs Ther 2006 Nov 20; 48 (1248): 95–6

    Google Scholar 

  56. Knowles SR, Shapiro L, Shear NH. Serious adverse reactions induced by minocycline: report of 13 patients and review of the literature. Arch Dermatol 1996 Aug; 132 (8): 934–9

    PubMed  CAS  Google Scholar 

  57. Liao DC. Management of acne. J Fam Pract 2003 Jan; 52 (1): 43–51

  58. Leyden JJ, Del Rosso JQ, Webster GF. Clinical considerations in the treatment of acne vulgaris and other inflammatory skin disorders: focus on antibiotic resistance. Cutis 2007 Jun; 79 (6 Suppl.): 9–25

  59. Eady EA, Gloor M, Leyden JJ. Propionibacterium acnes resistance: a worldwide problem. Dermatology 2003; 206 (1): 54–6

    PubMed  CAS  Google Scholar 

  60. Eady EA, Cove JH, Holland KT, et al. Erythromycin resistant propionibacteria in antibiotic treated acne patients: association with therapeutic failure. Br J Dermatol 1989 Jul; 121 (1): 51–7

    PubMed  CAS  Google Scholar 

  61. Margolis DJ, Bowe WP, Hoffstad O, et al. Antibiotic treatment of acne may be associated with upper respiratory tract infections. Arch Dermatol 2005 Sep; 141 (9): 1132–6

    PubMed  CAS  Google Scholar 

  62. Eady EA, Farmery MR, Ross JI, et al. Effects of benzoyl peroxide and erythromycin alone and in combination against antibiotic-sensitive and -resistant skin bacteria from acne patients. Br J Dermatol 1994 Sep; 131 (3): 331–6

    PubMed  CAS  Google Scholar 

  63. Dreno B, Bettoli V, Ochsendorf F, et al. European recommendations on the use of oral antibiotics for acne. Eur J Dermatol 2004 Nov-Dec; 14 (6): 391–9

    PubMed  Google Scholar 

  64. Del Rosso JQ, Leyden JJ. Status report on antibiotic resistance: implications for the dermatologist. Dermatol Clin 2007 Apr; 25 (2): 127–32, v

  65. Eady EA, Bojar RA, Jones CE, et al. The effects of acne treatment with a combination of benzoyl peroxide and erythromycin on skin carriage of erythromycin- resistant propionibacteria. Br J Dermatol 1996 Jan; 134 (1): 107–13

    PubMed  CAS  Google Scholar 

  66. Mills Jr OH, Kligman AM, Pochi P, et al. Comparing 2.5%, 5%, and 10% benzoyl peroxide on inflammatory acne vulgaris. Int J Dermatol 1986 Dec; 25 (10): 664–7

  67. Fanta D, Muller MM. Effect of benzoyl peroxide on skin surface lipids. Dermatologica 1979; 158 (1): 55–9

    PubMed  CAS  Google Scholar 

  68. Chalker DK, Shalita A, Smith Jr JG, et al. A double-blind study of the effectiveness of a 3% erythromycin and 5% benzoyl peroxide combination in the treatment of acne vulgaris. J Am Acad Dermatol 1983 Dec; 9 (6): 933–6

  69. Tschen EH, Katz HI, Jones TM, et al. A combination benzoyl peroxide and clindamycin topical gel compared with benzoyl peroxide, clindamycin phosphate, and vehicle in the treatment of acne vulgaris. Cutis 2001 Feb; 67 (2): 165–9

  70. Thiboutot DM, Weiss J, Bucko A, et al. Adapalene-benzoyl peroxide, a fixeddose combination for the treatment of acne vulgaris: results of a multicenter, randomized double-blind, controlled study. J Am Acad Dermatol 2007 Nov; 57 (5): 791–9

    PubMed  Google Scholar 

  71. Bowman S, Gold M, Nasir A, et al. Comparison of clindamycin/benzoyl peroxide, tretinoin plus clindamycin, and the combination of clindamycin/benzoyl peroxide and tretinoin plus clindamycin in the treatment of acne vulgaris: a randomized, blinded study. J Drugs Dermatol 2005 Sep-Oct; 4 (5): 611–8

  72. Leyden JJ. Topical treatment of acne vulgaris: retinoids and cutaneous irritation. J Am Acad Dermatol 1998 Apr; 38 (4): S1–4

    PubMed  CAS  Google Scholar 

  73. Thielitz A, Abdel-Naser MB, Fluhr JW, et al. Topical retinoids in acne: an evidence-based overview. J Dtsch Dermatol Ges 2008 Dec; 6 (12): 1023–31

    PubMed  Google Scholar 

  74. Jain S. Topical tretinoin or adapalene in acne vulgaris: an overview. J Dermatolog Treat 2004 Jul; 15 (4): 200–7

    CAS  Google Scholar 

  75. Kligman AM. How to use topical tretinoin in treating acne. Cutis 1995 Aug; 56 (2): 83–4

  76. Leyden JJ, Grossman R, Nighland M. Cumulative irritation potential of topical retinoid formulations. J Drugs Dermatol 2008 Aug; 7 (8 Suppl.)s: s14–8

    PubMed  Google Scholar 

  77. Beylot C, Doutre MS, Beylot-Barry M. Oral contraceptives and cyproterone acetate in female acne treatment. Dermatology 1998; 196 (1): 148–52

    PubMed  CAS  Google Scholar 

  78. Palombo-Kinne E, Schellschmidt I, Schumacher U, et al. Efficacy of a combined oral contraceptive containing 0.030 mg ethinylestradiol/2mg dienogest for the treatment of papulopustular acne in comparison with placebo and 0.035 mg ethinylestradiol/2mg cyproterone acetate. Contraception 2009 Apr; 79 (4): 282–9

    PubMed  CAS  Google Scholar 

  79. Johnson BA, Nunley JR. Use of systemic agents in the treatment of acne vulgaris. Am Fam Physician 2000 Oct 15; 62 (8): 1823–30, 1835-6

  80. Goulden V, Clark SM, Cunliffe WJ. Post-adolescent acne: a review of clinical features. Br J Dermatol 1997 Jan; 136 (1): 66–70

    PubMed  CAS  Google Scholar 

  81. Diamanti-Kandarakis E. Current aspects of antiandrogen therapy in women. Curr Pharm Des 1999 Sep; 5 (9): 707–23

  82. Bunker CB, Newton JA, Kilborn J, et al. Most women with acne have polycystic ovaries. Br J Dermatol 1989 Dec; 121 (6): 675–80

    PubMed  CAS  Google Scholar 

  83. Timpatanapong P, Rojanasakul A. Hormonal profiles and prevalence of polycystic ovary syndrome in women with acne. J Dermatol 1997 Apr; 24 (4): 223–9

    PubMed  CAS  Google Scholar 

  84. Lucky AW, Henderson TA, Olson WH, et al. Effectiveness of norgestimate and ethinyl estradiol in treating moderate acne vulgaris. J Am Acad Dermatol 1997 Nov; 37 (5 Pt 1): 746–54

    PubMed  CAS  Google Scholar 

  85. Thiboutot DM. Endocrinological evaluation and hormonal therapy for women with difficult acne. J Eur Acad Dermatol Venereol 2001; 15 Suppl. 3: 57–61

    PubMed  Google Scholar 

  86. Katsambas AD, Dessinioti C. Hormonal therapy for acne: why not as first line therapy? Facts and controversies. Clin Dermatol 2010 Jan-Feb; 28 (1): 17–23

    PubMed  Google Scholar 

  87. Levine RM, Rasmussen JE. Intralesional corticosteroids in the treatment of nodulocystic acne. Arch Dermatol 1983 Jun; 119 (6): 480–1

    PubMed  CAS  Google Scholar 

  88. Mahajan BB, Garg G. Therapeutic efficacy of intralesional triamcinolone acetonide versus intralesional triamcinolone acetonide plus lincomycin in the treatment of nodulocystic acne. Indian J Dermatol Venereol Leprol 2003 May-Jun; 69 (3): 217–9

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Acknowledgments

This review was funded in part by The Belgian American Educational Foundation (BAEF Fellow; C. Heughebaert). Dr Shalita is a consultant for Medicis Pharmaceuticals, Stiefel Laboratories, and Allergan, and has received honoraria from Allergan, Galderma, Medicis Pharmaceuticals, Stiefel Laboratories, and Johnson and Johnson. He holds stock in Allergan, Medicis Pharmaceuticals, and Johnson and Johnson. Drs Newman, Bowe, and Heughebaert have no conflicts of interest that are directly relevant to this review.

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  1. Department of Internal Medicine, New York Presbyterian-Weill Cornell Medical Center, New York, New York, USA

    Marissa D. Newman

  2. Department of Dermatology, SUNY Downstate Medical Center, 450 Clarkson Avenue, 11203, Brooklyn, New York, USA

    Whitney P. Bowe, Carol Heughebaert & Alan R. Shalita

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  1. Marissa D. Newman
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  2. Whitney P. Bowe
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Correspondence to Carol Heughebaert.

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Newman, M.D., Bowe, W.P., Heughebaert, C. et al. Therapeutic Considerations for Severe Nodular Acne. Am J Clin Dermatol 12, 7–14 (2011). https://doi.org/10.2165/11532280-000000000-00000

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