Skip to main content
SpringerLink
Log in

Biologic Therapy in the Treatment of Cutaneous Sarcoidosis: A Literature Review

  • Review Article
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Sarcoidosis is an inflammatory disease defined by the presence of non-caseating granulomas. It can affect a number of organ systems, most commonly the lungs, lymph nodes, and skin. Cutaneous manifestations of sarcoidosis can impose a significant detriment to patients’ quality of life. The accepted first-line therapy for cutaneous sarcoidosis consists of intralesional and oral corticosteroids, but these can fail in the face of resistant disease and corticosteroid-induced adverse effects. Second-line agents include tetracyclines, hydroxychloroquine, and methotrexate. Biologics are an emerging treatment option for the management of cutaneous sarcoidosis, but their role in management is not well-defined. In this article, we reviewed the currently available English-language publications on the use of biologics in managing cutaneous sarcoidosis. Although somewhat limited, the data in published studies support the use of both infliximab and adalimumab as third-line treatments for chronic or resistant cutaneous sarcoidosis. There were also scattered reports of etanercept, rituximab, golimumab, and ustekinumab being utilized as third-line agents with varying degrees of success. Larger and more extensive investigations are required to further assess the adverse effect profile and optimal dosing for managing cutaneous sarcoidosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Haimovic A, Sanchez M, Judson MA, Prystowsky S. Sarcoidosis: a comprehensive review and update for the dermatologist: part I. Cutaneous disease. J Am Acad Dermatol. 2012;66(5):699 e1–18 (quiz 717–8).

    Article  Google Scholar 

  2. Petit A, Dadzie OE. Multisystemic diseases and ethnicity: a focus on lupus erythematosus, systemic sclerosis, sarcoidosis and Behcet disease. Br J Dermatol. 2013;169(Suppl 3):1–10.

    Article  PubMed  Google Scholar 

  3. Heath CR, David J, Taylor SC. Sarcoidosis: are there differences in your skin of color patients? J Am Acad Dermatol. 2012;66(1):121 e1–14.

  4. Doherty CB, Rosen T. Evidence-based therapy for cutaneous sarcoidosis. Drugs. 2008;68(10):1361–83.

    Article  CAS  PubMed  Google Scholar 

  5. Volden G. Successful treatment of chronic skin diseases with clobetasol propionate and a hydrocolloid occlusive dressing. Acta Dermatovenereol. 1992;72(1):69–71.

    CAS  Google Scholar 

  6. Baughman RP, Lower EE. Evidence-based therapy for cutaneous sarcoidosis. Clin Dermatol. 2007;25(3):334–40.

    Article  PubMed  Google Scholar 

  7. Fetil E, Ozkan S, Ilknur T, Kavukcu S, Kusku E, Lebe B. Sarcoidosis in a preschooler with only skin and joint involvement. Pediatr Dermatol. 2003;20(5):416–8.

    Article  PubMed  Google Scholar 

  8. Pariser RJ, Paul J, Hirano S, Torosky C, Smith M. A double-blind, randomized, placebo-controlled trial of adalimumab in the treatment of cutaneous sarcoidosis. J Am Acad Dermatol. 2013;68(5):765–73.

    Article  CAS  PubMed  Google Scholar 

  9. Heidelberger V, Ingen-Housz-Oro S, Marquet A, Mahevas M, Bessis D, Bouillet L, et al. Efficacy and tolerance of anti-tumor necrosis factor alpha agents in cutaneous sarcoidosis: a French Study of 46 cases. JAMA Dermatol. 2017;153(7):681–5.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Jamilloux Y, Cohen-Aubart F, Chapelon-Abric C, Maucort-Boulch D, Marquet A, Perard L, et al. Efficacy and safety of tumor necrosis factor antagonists in refractory sarcoidosis: a multicenter study of 132 patients. Semin Arthr Rheum. 2017;47(2):288–94.

    Article  CAS  Google Scholar 

  11. Judson MA, Baughman RP, Costabel U, Flavin S, Lo KH, Kavuru MS, et al. Efficacy of infliximab in extrapulmonary sarcoidosis: results from a randomised trial. Eur Respir J. 2008;31(6):1189–96.

    Article  CAS  PubMed  Google Scholar 

  12. Baughman RP, Drent M, Kavuru M, Judson MA, Costabel U, du Bois R, et al. Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med. 2006;174(7):795–802.

    Article  CAS  PubMed  Google Scholar 

  13. Baughman RP, Judson MA, Lower EE, Drent M, Costabel U, Flavin S, et al. Infliximab for chronic cutaneous sarcoidosis: a subset analysis from a double-blind randomized clinical trial. Sarcoidosis Vasc Diffuse Lung Dis. 2016;32(4):289–95.

    PubMed  Google Scholar 

  14. Stagaki E, Mountford WK, Lackland DT, Judson MA. The treatment of lupus pernio: results of 116 treatment courses in 54 patients. Chest. 2009;135(2):468–76.

    Article  PubMed  Google Scholar 

  15. Baughman RP, Lower EE. Infliximab for refractory sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2001;18(1):70–4.

    CAS  PubMed  Google Scholar 

  16. Mallbris L, Ljungberg A, Hedblad MA, Larsson P, Stahle-Backdahl M. Progressive cutaneous sarcoidosis responding to anti-tumor necrosis factor-alpha therapy. J Am Acad Dermatol. 2003;48(2):290–3.

    Article  PubMed  Google Scholar 

  17. Crouser ED, Lozanski G, Fox CC, Hauswirth DW, Raveendran R, Julian MW. The CD4+ lymphopenic sarcoidosis phenotype is highly responsive to anti-tumor necrosis factor-{alpha} therapy. Chest. 2010;137(6):1432–5.

    Article  CAS  PubMed  Google Scholar 

  18. Saleh S, Ghodsian S, Yakimova V, Henderson J, Sharma OP. Effectiveness of infliximab in treating selected patients with sarcoidosis. Respir Med. 2006;100(11):2053–9.

    Article  PubMed  Google Scholar 

  19. Chung J, Rosenbach M. Extensive cutaneous sarcoidosis and coexistant Crohn disease with dual response to infliximab: case report and review of the literature. Dermatol Online J. 2014;21(3).

  20. Tuchinda P, Bremmer M, Gaspari AA. A case series of refractory cutaneous sarcoidosis successfully treated with infliximab. Dermatol Ther. 2012;2(1):11.

    Article  Google Scholar 

  21. Sene T, Juillard C, Rybojad M, Cordoliani F, Lebbe C, Morel P, et al. Infliximab as a steroid-sparing agent in refractory cutaneous sarcoidosis: single-center retrospective study of 9 patients. J Am Acad Dermatol. 2012;66(2):328–32.

    Article  CAS  PubMed  Google Scholar 

  22. Cerniglia B, Judson MA. Infliximab-induced hypothyroidism: a novel case and postulations concerning the mechanism. Case Rep Med. 2013;2013:216939.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Tu J, Chan J. Cutaneous sarcoidosis and infliximab: evidence for efficacy in refractory disease. Australas J Dermatol. 2014;55(4):279–81.

    Article  PubMed  Google Scholar 

  24. Sweiss NJ, Welsch MJ, Curran JJ, Ellman MH. Tumor necrosis factor inhibition as a novel treatment for refractory sarcoidosis. Arthr Rheum. 2005;53(5):788–91.

    Article  CAS  Google Scholar 

  25. Rosen T, Doherty C. Successful long-term management of refractory cutaneous and upper airway sarcoidosis with periodic infliximab infusion. Dermatol Online J. 2007;13(3):14.

    PubMed  Google Scholar 

  26. Blanco R, Gonzalez-Gay MA, Gonzalez-Lopez MA, Fernandez-Llaca H, Gonzalez-Vela MC. Refractory highly disfiguring lupus pernio: a dramatic and prolonged response to infliximab. Int J Dermatol. 2015;54(8):e321–2.

    Article  CAS  PubMed  Google Scholar 

  27. Thielen AM, Barde C, Saurat JH, Laffitte E. Refractory chronic cutaneous sarcoidosis responsive to dose escalation of TNF-alpha antagonists. Dermatology. 2009;219(1):59–62.

    Article  CAS  PubMed  Google Scholar 

  28. Wanat KA, Rosenbach M. Case series demonstrating improvement in chronic cutaneous sarcoidosis following treatment with TNF inhibitors. Arch Dermatol. 2012;148(9):1097–100.

    Article  PubMed  Google Scholar 

  29. Panselinas E, Rodgers JK, Judson MA. Clinical outcomes in sarcoidosis after cessation of infliximab treatment. Respirology. 2009;14(4):522–8.

    Article  PubMed  Google Scholar 

  30. Heffernan MP, Anadkat MJ. Recalcitrant cutaneous sarcoidosis responding to infliximab. Arch Dermatol. 2005;141(7):910–1.

    Article  PubMed  Google Scholar 

  31. Haley H, Cantrell W, Smith K. Infliximab therapy for sarcoidosis (lupus pernio). Br J Dermatol. 2004;150(1):146–9.

    Article  CAS  PubMed  Google Scholar 

  32. Maneiro JR, Salgado E, Gomez-Reino JJ, Carmona L. Efficacy and safety of TNF antagonists in sarcoidosis: data from the Spanish registry of biologics BIOBADASER and a systematic review. Semin Arthr Rheum. 2012;42(1):89–103.

    Article  CAS  Google Scholar 

  33. Jounieaux F, Chapelon C, Valeyre D, Israel Biet D, Cottin V, Tazi A, et al. Infliximab treatment for chronic sarcoidosis: a case series (in French). Revue Mal Respir. 2010;27(7):685–92.

    Article  CAS  Google Scholar 

  34. Yee AM, Pochapin MB. Treatment of complicated sarcoidosis with infliximab anti-tumor necrosis factor-alpha therapy. Ann Intern Med. 2001;135(1):27–31.

    Article  CAS  PubMed  Google Scholar 

  35. Heffernan MP, Smith DI. Adalimumab for treatment of cutaneous sarcoidosis. Arch Dermatol. 2006;142(1):17–9.

    PubMed  Google Scholar 

  36. Mirzaei A, Joharimoghadam MM, Zabihiyeganeh M. Adalimumab-responsive refractory sarcoidosis following multiple eyebrow tattoos: a case report. Tanaffos. 2017;16(1):80–3.

    PubMed  PubMed Central  Google Scholar 

  37. Kaiser CA, Cozzio A, Hofbauer GF, Kamarashev J, French LE, Navarini AA. Disfiguring annular sarcoidosis improved by adalimumab. Case Rep Dermatol. 2011;3(2):103–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Philips MA, Lynch J, Azmi FH. Ulcerative cutaneous sarcoidosis responding to adalimumab. J Am Acad Dermatol. 2005;53(5):917.

    Article  PubMed  Google Scholar 

  39. Field S, Regan AO, Sheahan K, Collins P. Recalcitrant cutaneous sarcoidosis responding to adalimumab but not to etanercept. Clin Exp Dermatol. 2010;35(7):795–6.

    Article  CAS  PubMed  Google Scholar 

  40. Judson MA. Successful treatment of lupus pernio with adalimumab. Arch Dermatol. 2011;147(11):1332–3.

    Article  PubMed  Google Scholar 

  41. Cohen GF, Wolfe CM. Recalcitrant diffuse cutaneous sarcoidosis with perianal involvement responding to adalimumab. J Drugs Dermatol. 2017;16(12):1305–6.

    PubMed  Google Scholar 

  42. Hagan CE, Offiah M, Brodell RT, Jackson JD. Chronic verrucous sarcoidosis associated with human papillomavirus infection: improvement with adalimumab. JAAD Case Rep. 2018;4(9):866–8.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Tuchinda C, Wong HK. Etanercept for chronic progressive cutaneous sarcoidosis. J Drugs Dermatol. 2006;5(6):538–40.

    PubMed  Google Scholar 

  44. Khanna D, Liebling MR, Louie JS. Etanercept ameliorates sarcoidosis arthritis and skin disease. J Rheumatol. 2003;30(8):1864–7.

    PubMed  Google Scholar 

  45. Utz JP, Limper AH, Kalra S, Specks U, Scott JP, Vuk-Pavlovic Z, et al. Etanercept for the treatment of stage II and III progressive pulmonary sarcoidosis. Chest. 2003;124(1):177–85.

    Article  CAS  PubMed  Google Scholar 

  46. Papp KA. The safety of etanercept for the treatment of plaque psoriasis. Ther Clin Risk Manag. 2007;3(2):245–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Judson MA, Baughman RP, Costabel U, Drent M, Gibson KF, Raghu G, et al. Safety and efficacy of ustekinumab or golimumab in patients with chronic sarcoidosis. Eur Respir J. 2014;44(5):1296–307.

    Article  CAS  PubMed  Google Scholar 

  48. Bomprezzi R, Pati S, Chansakul C, Vollmer T. A case of neurosarcoidosis successfully treated with rituximab. Neurology. 2010;75(6):568–70.

    Article  PubMed  Google Scholar 

  49. Cinetto F, Compagno N, Scarpa R, Malipiero G, Agostini C. Rituximab in refractory sarcoidosis: a single centre experience. Clin Mol Allergy. 2015;13(1):19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Lamrock E, Brown P. Development of cutaneous sarcoidosis during treatment with tumour necrosis alpha factor antagonists. Australas J Dermatol. 2012;53(4):e87–90.

    Article  PubMed  Google Scholar 

  51. Marcella S, Welsh B, Foley P. Development of sarcoidosis during adalimumab therapy for chronic plaque psoriasis. Australas J Dermatol. 2011;52(3):e8–11.

    Article  PubMed  Google Scholar 

  52. Salvatierra J, Magro-Checa C, Rosales-Alexander JL, Raya-Alvarez E. Acute sarcoidosis as parotid fever in rheumatoid arthritis under anti-tumor necrosis factor-alpha therapy. Rheumatology (Oxford). 2011;50(7):1346–8.

    Article  PubMed  Google Scholar 

  53. Bonafede MM, Gandra SR, Watson C, Princic N, Fox KM. Cost per treated patient for etanercept, adalimumab, and infliximab across adult indications: a claims analysis. Adv Ther. 2012;29(3):234–48.

    Article  PubMed  Google Scholar 

  54. Keijsers RG, Verzijlbergen JF, van Diepen DM, van den Bosch JM, Grutters JC. 18F-FDG PET in sarcoidosis: an observational study in 12 patients treated with infliximab. Sarcoidosis Vasc Diffuse Lung Dis. 2008;25(2):143–9.

    CAS  PubMed  Google Scholar 

  55. Sweiss NJ, Barnathan ES, Lo K, Judson MA, Baughman R. C-reactive protein predicts response to infliximab in patients with chronic sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2010;27(1):49–56.

    CAS  PubMed  Google Scholar 

  56. Damsky W, Thakral D, Emeagwali N, Galan A, King B. Tofacitinib treatment and molecular analysis of cutaneous sarcoidosis. N Engl J Med. 2018;379(26):2540–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Rotenberg C, Besnard V, Brillet PY, Giraudier S, Nunes H, Valeyre D. Dramatic response of refractory sarcoidosis under ruxolitinib in a patient with associated JAK2-mutated polycythemia. Eur Respir J. 2018;52(6).

  58. Kono M, Kono M, Jodo S. A case of refractory acute sarcoid myopathy successfully treated with intravenous immunoglobulin. Scand J Rheumatol. 2018;47(2):168–9.

    Article  CAS  PubMed  Google Scholar 

  59. Linger MW, van Driel ML, Hollingworth SA. Off-label use of tumour necrosis factor-alpha inhibitors and anakinra at an Australian tertiary hospital. Intern Med J. 2016;46(12):1386–91.

    Article  CAS  PubMed  Google Scholar 

  60. Shenoy N, Tesfaye M, Brown J, Simmons N, Weiss D, Meholli M, et al. Corticosteroid-resistant bulbar neurosarcoidosis responsive to intravenous immunoglobulin. Pract Neurol. 2015;15(4):289–92.

    Article  PubMed  Google Scholar 

  61. Awano N, Inomata M, Kondoh K, Satake K, Kamiya H, Moriya A, et al. Mixed-type multicentric Castleman’s disease developing during a 17-year follow-up of sarcoidosis. Intern Med. 2012;51(21):3061–6.

    Article  PubMed  Google Scholar 

  62. Semiz H, Kobak S. Coexistence of sarcoidosis and adult onset Still disease. Reumatol Clin. https://doi.org/10.1016/j.reuma.2017.04.004 (epub 19 May 2017).

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, University of Central Florida College of Medicine, Health Sciences Campus at Lake Nona, 6850 Lake Nona Blvd, Orlando, FL, 32827-7408, USA

    Christina Dai, Shawn Shih, Ahmed Ansari & Naveed Sami

  2. DermSurgery Associates, 7515 S Main St #240, Houston, TX, 77030, USA

    Young Kwak

Authors
  1. Christina Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shawn Shih
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmed Ansari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Young Kwak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naveed Sami
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Naveed Sami.

Ethics declarations

Funding

No funding was received for the preparation of this review.

Conflict of interest

Christina Dai, Shawn Shih, Ahmed Ansari, and Young Kwak have no conflicts of interest to declare. Naveed Sami was a previous sub-investigator for Centocor clinical trial for sarcoidosis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dai, C., Shih, S., Ansari, A. et al. Biologic Therapy in the Treatment of Cutaneous Sarcoidosis: A Literature Review. Am J Clin Dermatol 20, 409–422 (2019). https://doi.org/10.1007/s40257-019-00428-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40257-019-00428-8

Search

Navigation