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Case Report/Case Series | The cutting Edge

Adalimumab for the Treatment of Refractory Acne Conglobata FREE

Freja Lærke Sand, BSc1; Simon Francis Thomsen, MD, PhD1
[+] Author Affiliations
1Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Denmark
JAMA Dermatol. 2013;149(11):1306-1307. doi:10.1001/jamadermatol.2013.6678.
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Published online

Tumor necrosis factor (TNF) inhibitors have become important components of the treatment of multiple chronic inflammatory disorders such as psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, Crohn disease, and ulcerative colitis. Furthermore, off-label use of TNF inhibitors has been reported for a variety of other diseases. We report a case of refractory acne conglobata treated with the TNF inhibitor adalimumab.

An 18-year-old otherwise healthy man presented with a 4-year history of multiple painful inflammatory nodular lesions and sinus tracts on the face (Figure, A). His skin lesions were confined to the face; he did not present with fever; and he had no symptoms or signs indicating a systemic inflammatory disease such as inflammatory bowel disease or arthritis. Prior to admission, he had received unsuccessful therapy with doxycycline, 100 mg, twice daily for 6 months; oral isotretinoin, 0.5 mg/kg/d, for 3 months, which was later increased to 1.0 mg/kg/d in combination with prednisolone, 1.0 mg/kg/d for 2 months; and oral isotretinoin, 0.75 mg/kg/d in combination with dapsone, 50 mg, twice daily for 2 months.

Place holder to copy figure label and caption
Figure.
Facial Acne Conglobata Before and After Treatment With Adalimumab

A, Study patient with severe facial nodular inflammatory acne. B, Clearance 3 months after initiation of treatment with adalimumab, 40 mg, twice monthly.

Graphic Jump Location

The patient was diagnosed as having severe acne conglobata, which is unresponsive to doxycycline, isotretinoin, prednisolone, and dapsone. We initiated monotherapy with adalimumab using an initial loading dose of 80 mg, followed by 40 mg twice monthly. A marked decrease was observed in the size and degree of inflammation of the nodular lesions already 4weeks after initiating treatment, and after 12 weeks of therapy, all nodular lesions had disappeared (Figure, B). At last follow-up, the patient had received continuous monotherapy with adalimumab, 40 mg, twice monthly for a total of 12 months, and he had sustained efficacy without recurrence of acne lesions. No adverse events were recorded, and all routine laboratory test results were within normal limits.

To our knowledge, this is the first time adalimumab has been used successfully as monotherapy in a patient with therapy-resistant acne conglobata. Previously, 1 patient with facial acne conglobata responded rapidly to treatment with etanercept1; another patient with acne conglobata and concomitant rheumatoid arthritis responded to infliximab in combination with oral isotretinoin2; and finally, a patient with severe nodular inflammatory acne and ulcerative colitis, which was in complete remission with azathioprine treatment, was treated successfully with infliximab.3

Acne is an inflammatory condition marked by elevations in certain cytokines, including tumor necrosis factor (TNF), interleukin 1β, and granulocyte-macrophage colony stimulating factor. Propionibacterium acnes has been a suggested trigger of this inflammation by stimulating production of TNF from keratinocytes.4 The upregulation of TNF in acne therefore theoretically supports the use of TNF inhibitors for this indication.

Enigmatically, acne has been reported as a paradoxical adverse reaction to treatment with TNF inhibitors, primarily in patients with inflammatory bowel disease.5 Similarly, paradoxical induction of psoriasis in patients with inflammatory bowel disease or rheumatoid arthritis has also been observed in patients treated with TNF inhibitors, and substituting the offending agent with a different TNF inhibitor may not necessarily alleviate symptoms. These observations indicate a complex role of TNF in the inflammatory response in several skin diseases such as acne and psoriasis and signal that the delicate balance between several cytokines may be important for the induction of disease and for the response to treatment. Research aimed at elucidating these mechanisms is warranted.

Tumor necrosis factor inhibitors have been used successfully to treat patients with SAPHO syndrome, characterized by synovitis, acne, pustulosis, hyperostosis, and osteitis. Skin manifestations in patients with SAPHO syndrome may be acne fulminans, acne conglobata, palmoplantar pustulosis, or hidradenitis suppurativa. In several case reports and patient series, TNF inhibitors, mainly infliximab, have proved effective in patients with SAPHO syndrome. One patient with severe SAPHO syndrome responded to a combination of isotretinoin and adalimumab.6

Patients with pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) have a hereditary autoinflammatory syndrome characterized by increased production of TNF by mononuclear cells, and in 1 case, treatment with etanercept resulted in sustained clinical remission.7 Similarly, therapy with infliximab and adalimumab has also demonstrated efficacy in patients with PAPA.8,9

PASH syndrome (pyoderma gangrenosum, acne and suppurative hidradenitis), which is distinctly different from PAPA in that arthritis is absent, has recently been described. Interestingly, all dermatologic and rheumatologic manifestations completely resolved following treatment with infliximab in a patient with PASH.10

Because acne is part of the clinical manifestations of SAPHO, PAPA, and PASH, and because the efficacy of TNF inhibitors has been demonstrated in all 3 syndromes, it is proposed that this group of agents could be considered also in selected patients with severe primary recalcitrant acne. The patient described herein was treated continuously for 12 months with adalimumab and had sustained and marked reduction in symptoms. However, durability of remission is unknown, and therefore the present evidence does not support a curative role of TNF inhibitors in acne.

Section Editor: Edward W. Cowen, MD, MHSc; Assistant Section Editors: Murad Alam, MD; Ruth Ann Vleugels, MD.

Corresponding Author: Simon Francis Thomsen, MD, PhD, Department of Dermatology, Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark (sft@city.dk).

Accepted for Publication: July 9, 2013.

Published Online: September 18, 2013. doi:10.1001/jamadermatol.2013.6678.

Author Contributions: Both authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Both authors.

Acquisition of data: Thomsen.

Analysis and interpretation of data: Both authors.

Drafting of the manuscript: Sand.

Critical revision of the manuscript for important intellectual content: Both authors.

Statistical analysis: Thomsen.

Study supervision: Thomsen.

Conflict of Interest Disclosures: None reported.

Additional Contributions: We are indebted to Nis Kentorp, clinical photographer, for producing the illustrations. Mr Kentorp received no financial remuneration for his contribution.

Campione  E, Mazzotta  AM, Bianchi  L, Chimenti  S.  Severe acne successfully treated with etanercept. Acta Derm Venereol. 2006;86(3):256-257.
PubMed   |  Link to Article
Shirakawa  M, Uramoto  K, Harada  FA.  Treatment of acne conglobata with infliximab. J Am Acad Dermatol. 2006;55(2):344-346.
PubMed   |  Link to Article
Schuttelaar  ML, Leeman  FW.  Sustained remission of nodular inflammatory acne after treatment with infliximab. Clin Exp Dermatol. 2011;36(6):670-671.
PubMed   |  Link to Article
Graham  GM, Farrar  MD, Cruse-Sawyer  JE, Holland  KT, Ingham  E.  Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL. Br J Dermatol. 2004;150(3):421-428.
PubMed   |  Link to Article
Cleynen  I, Vermeire  S.  Paradoxical inflammation induced by anti-TNF agents in patients with IBD. Nat Rev Gastroenterol Hepatol. 2012;9(9):496-503.
PubMed   |  Link to Article
Garcovich  S, Amelia  R, Magarelli  N, Valenza  V, Amerio  P.  Long-term treatment of severe SAPHO syndrome with adalimumab. Am J Clin Dermatol. 2012;13(1):55-59.
PubMed   |  Link to Article
Cortis  E, De Benedetti  F, Insalaco  A,  et al.  Abnormal production of tumor necrosis factor (TNF)-alpha and clinical efficacy of the TNF inhibitor etanercept in a patient with PAPA syndrome [corrected]. J Pediatr. 2004;145(6):851-855.
PubMed   |  Link to Article
Tofteland  ND, Shaver  TS.  Clinical efficacy of etanercept for treatment of PAPA syndrome. J Clin Rheumatol. 2010;16(5):244-245.
PubMed   |  Link to Article
Lee  H, Park  SH, Kim  SK, Choe  JY, Park  JS.  Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome) with E250K mutation in CD2BP1 gene treated with the tumor necrosis factor inhibitor adalimumab. Clin Exp Rheumatol. 2012;30(3):452.
PubMed
Bruzzese  V.  Pyoderma gangrenosum, acne conglobata, suppurative hidradenitis, and axial spondyloarthritis: efficacy of anti-tumor necrosis factor α therapy. J Clin Rheumatol. 2012;18(8):413-415.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure.
Facial Acne Conglobata Before and After Treatment With Adalimumab

A, Study patient with severe facial nodular inflammatory acne. B, Clearance 3 months after initiation of treatment with adalimumab, 40 mg, twice monthly.

Graphic Jump Location

Tables

References

Campione  E, Mazzotta  AM, Bianchi  L, Chimenti  S.  Severe acne successfully treated with etanercept. Acta Derm Venereol. 2006;86(3):256-257.
PubMed   |  Link to Article
Shirakawa  M, Uramoto  K, Harada  FA.  Treatment of acne conglobata with infliximab. J Am Acad Dermatol. 2006;55(2):344-346.
PubMed   |  Link to Article
Schuttelaar  ML, Leeman  FW.  Sustained remission of nodular inflammatory acne after treatment with infliximab. Clin Exp Dermatol. 2011;36(6):670-671.
PubMed   |  Link to Article
Graham  GM, Farrar  MD, Cruse-Sawyer  JE, Holland  KT, Ingham  E.  Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL. Br J Dermatol. 2004;150(3):421-428.
PubMed   |  Link to Article
Cleynen  I, Vermeire  S.  Paradoxical inflammation induced by anti-TNF agents in patients with IBD. Nat Rev Gastroenterol Hepatol. 2012;9(9):496-503.
PubMed   |  Link to Article
Garcovich  S, Amelia  R, Magarelli  N, Valenza  V, Amerio  P.  Long-term treatment of severe SAPHO syndrome with adalimumab. Am J Clin Dermatol. 2012;13(1):55-59.
PubMed   |  Link to Article
Cortis  E, De Benedetti  F, Insalaco  A,  et al.  Abnormal production of tumor necrosis factor (TNF)-alpha and clinical efficacy of the TNF inhibitor etanercept in a patient with PAPA syndrome [corrected]. J Pediatr. 2004;145(6):851-855.
PubMed   |  Link to Article
Tofteland  ND, Shaver  TS.  Clinical efficacy of etanercept for treatment of PAPA syndrome. J Clin Rheumatol. 2010;16(5):244-245.
PubMed   |  Link to Article
Lee  H, Park  SH, Kim  SK, Choe  JY, Park  JS.  Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome) with E250K mutation in CD2BP1 gene treated with the tumor necrosis factor inhibitor adalimumab. Clin Exp Rheumatol. 2012;30(3):452.
PubMed
Bruzzese  V.  Pyoderma gangrenosum, acne conglobata, suppurative hidradenitis, and axial spondyloarthritis: efficacy of anti-tumor necrosis factor α therapy. J Clin Rheumatol. 2012;18(8):413-415.
PubMed   |  Link to Article

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