Good Response of Acne Conglobata to Adalimumab in Two Patients with Hidradenitis Suppurativa

Acne conglobata is a form of nodulocystic acne characterized by abscesses, sinuses and large comodones that can lead to hypertrophic and atrophic scarring. The condition may result in marked disfigurement and a significant effect on the quality of life. It frequently affects the back, chest, shoulders, upper arms, thighs and the face. Acne conglabata may occur as a recurrence of previously dormant acne or as a result of a sudden deterioration in existing papular or pustular acne. It is usually associated with Follicular Occlusion Syndrome in particular Hidradenitis Suppurativa, dissecting folliculitis and pilonidal sinus. Treatment can be challenging with options including antibiotics, oral steroids, intralesional steroids and oral isotretinoin. There is evolving evidence that anti-TNF α therapy is effective in the management of severe recalcitrant inflammatory acne [1]. We report two cases of good response of acne conglobate in two patients with HS treated with adalimumab.


Introduction
Acne conglobata is a form of nodulocystic acne characterized by abscesses, sinuses and large comodones that can lead to hypertrophic and atrophic scarring. The condition may result in marked disfigurement and a significant effect on the quality of life. It frequently affects the back, chest, shoulders, upper arms, thighs and the face. Acne conglabata may occur as a recurrence of previously dormant acne or as a result of a sudden deterioration in existing papular or pustular acne. It is usually associated with Follicular Occlusion Syndrome in particular Hidradenitis Suppurativa, dissecting folliculitis and pilonidal sinus. Treatment can be challenging with options including antibiotics, oral steroids, intralesional steroids and oral isotretinoin. There is evolving evidence that anti-TNF α therapy is effective in the management of severe recalcitrant inflammatory acne [1]. We report two cases of good response of acne conglobate in two patients with HS treated with adalimumab.

Report
The first patient was a 44 year old male who has had a long standing history of painful, nodulocystic acne since the age of 12 mainly affecting his back. He received two course of oral isotretinoin at the age of 20 and 30. In his 20s he developed psoriasis that was managed with topical treatment only. Ten years later he began to develop painful boils intermittently in his groin and axillary areas. At the age of 40, he had a recurrent flare up of his acne requiring referral to the Dermatology Department for further management.
At presentation, he had moderately severe nodulocycstic acne with atrophic scarring on his back. He had erythematous nodules in his groin and axillary areas with double comedones consistent with Hidradenitis Suppurativa. There were psoriatic plaques in groin area as

Clinical & Experimental Dermatology Research
well as evidence of pitting on the right finger nails. His PASI score was 10.4.
Failing multiple lines of antibiotics including Rifampicin and Clindamycin combination, as well as Isotretinoin, he was commenced on Adalimumab at 80 mg loading dose followed by 40 mg every other week as a monotherapy. At his 12 week follow up, he had made a significant improvement in his acne conglobata and Hidradenitis Suppurativa with minimal activity and flare ups ( Figure 1). His PASI score was 4.2.
The second case is a 55 year old gentleman with a long history of severe nodulocystic acne affecting his face and back and a 25 year history of Hidradenitis Suppurativa. Previous failed treatment for his acne includes trimethoprim, minocycline and isotretinoin at a dose of 0.75 mg/kg. He was commenced on Rifampicin and Clindamycin combination therapy for his recurrent flare ups of Hurley Stage 2 Hidradenitis Suppurativa but had suboptimal response to after 10 weeks. He was then commenced on Adalimumab at 80 mg loading dose followed by 40 mg fortnightly as a monotherapy mainly for his Hidradenitis Suppurativa. At his 1 year follow up, his Hidradenitis Suppurativa was quiescent and his acne conglobata had simultaneously improved with minimal flare ups or activity (Figure 2).

Discussion
Isolated case reports in the literature have shown that anti-TNFα therapies are effective in treatment of acne conglobata presenting in isolation or as part of systemic inflammatory conditions including synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO syndrome) [2].
To our knowledge, there has only been one other case reported in the literature to date which describes successful treatment of refractory acne conglobata with Adalimumab as monotherapy [3]. This case reported by Sand et al. describes an 18 year old man who had severe acne conglobata which was unresponsive to doxycycline, isotretinoin, prednisolone and dapsone. Adalimumab was initiated as a monotherapy with a loading dose of 80 mg, followed by 40 mg twice monthly subcutaneously which resulted in a marked decrease in the size and degree of inflammation of the nodular lesions at 4 weeks after commencement of treatment with a sustained efficacy for 12 months with no recurrence of acne lesions. Both Etanercept and Infliximab have also been reported in the literature in several cases to be effective therapies in patients with severe nodulocystic acne, both in isolated cutaneous disease and in association with SAPHO syndrome [4][5][6][7][8].
Acne is an inflammatory condition characterized by significant elevations in Propionibacterium acnes that subsequently triggers keratinocytes to produce particular cytokines including tumour necrosis factor (TNFα) and interleukin (IL)-1α [9]. Furthermore, a study by Cailion et al. showed that P. acnes stimulated significantly higher levels of TNF α and IL-8 compared to controls explaining the benefit of anti-TNF therapies in inflammatory conditions such as acne conglobata by the blockage of this inflammatory cascade [10].
It is however an unusual but well acknowledged phenomenon that anti-TNF therapies can trigger inflammatory skin conditions with a common one being psoriasiform skin eruptions. This appears to be paradoxical as TNF α is a pivotal molecule in the pathogenesis of psoriasis. There have been several case reports also describing acne being triggered by anti-TNF therapies suggesting that the delicate balance between cytokines may be important for the induction of disease and for the response to treatment [11].

Conclusion
In conclusion, Adalimumab appears to be an effective treatment option in patients with severe acne conglobata resistant to conventional therapies based on the two cases we have reported in addition to cases described in the literature thus far. Although both our patients maintained response to treatment at 12 weeks and 1 year, the durability of remission is unknown. Interestingly both patients had a good response at the lower dosage regimen of 40 mg once fortnightly than 40 mg once weekly as is recommended for HS. Therefore, larger scale, double-blinded, randomized, placebo-controlled and long term follow up studies are essential to elucidate the efficacy and safety of anti-TNF therapies in the treatment of acne conglobata as well as its durability of remission.