PsAPASH: A new syndrome associated with hidradenitis suppurativa with response to tumor necrosis factor inhibition
Authors: Rosita Saraceno, Graziella Babino, Andrea Chiricozzi, Arianna Zangrilli, Sergio Chimenti
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: A 50-year-old man with refractory and multitherapy-resistant hidradenitis suppurativa was referred for evaluation after having been unsuccessfully treated with dapsone, oral isotretinoin, and several cycles of antibiotics (clindamycin-rifampin, tetracycline, cephalosporin) (Fig 1, A). He had hidradenitis suppurativa since the age of 43 years, was overweight and a heavy tobacco smoker, and had a medical history of acne, diabetes mellitus type 2, arterial hypertension, hypertriglyceridemia, hiatal hernia, depression, and psoriatic arthritis (PsA). Active acne pustules and comedonal lesions were observed on the face and neck; painful sterile abscesses and hypertrophic scars were present at the axillae and were classified as hidradenitis suppurativa Hurley II stage of severity. The patient had also erythematous scaly lesions on the scalp associated with severe joint and diffuse inflammation leading to the clinical diagnosis of PsA (Psoriasis Area Severity Index score 1.2; DAS28-CRP4 5.78; pain visual analog scale score 70). Two ulcerative lesions on his right leg had a dusky erythematous undermined edge (Fig 1, B), and were clinically and histologically diagnosed as pyoderma gangrenosum after the exclusion of diagnoses including neutrophilic disorders, vasculopathies, and infections. His quality of life was severely hampered by disability and social discomfort.Adalimumab is a highly specific tumor necrosis factor (TNF)-alfa inhibitor, binding to both soluble and membrane-bound TNF-alfa. TNF-alfa is a proinflammatory cytokine with a pathogenetic role in several immune-mediated diseases such as psoriasis, hidradenitis suppurativa, and pyoderma gangrenosum. The efficacy and safety of adalimumab in treating PsA is largely demonstrated, whereas limited evidence of its off-label use in treating hidradenitis suppurativa, pyoderma gangrenosum, or concomitant skin disorders has been reported.1Miller I. Lynggaard C.D. Lophaven S. Zachariae C. Dufour D.N. Jemec G.B. A double-blind placebo-controlled randomized trial of adalimumab in the treatment of hidradenitis suppurativa.Br J Dermatol. 2011; 165: 391-398Crossref PubMed Scopus (158) Google Scholar, 2Kimball A.B. Kerdel F. Adams D. et al.Adalimumab for the treatment of moderate to severe hidradenitis suppurativa: a parallel randomized trial.Ann Intern Med. 2012; 157: 846-855Crossref PubMed Scopus (311) Google Scholar, 3Reddick C.L. Singh M.N. Chalmers R.J. Successful treatment of superficial pyoderma gangrenosum associated with hidradenitis suppurativa with adalimumab.Dermatol Online J. 2010; 16: 15PubMed Google Scholar Randomized, double-blind, placebo-controlled studies have assessed the efficacy and safety of adalimumab therapy in patients affected by hidradenitis suppurativa.1Miller I. Lynggaard C.D. Lophaven S. Zachariae C. Dufour D.N. Jemec G.B. A double-blind placebo-controlled randomized trial of adalimumab in the treatment of hidradenitis suppurativa.Br J Dermatol. 2011; 165: 391-398Crossref PubMed Scopus (158) Google Scholar, 2Kimball A.B. Kerdel F. Adams D. et al.Adalimumab for the treatment of moderate to severe hidradenitis suppurativa: a parallel randomized trial.Ann Intern Med. 2012; 157: 846-855Crossref PubMed Scopus (311) Google ScholarAdalimumab therapy was initiated at a dose of 40 mg every other week. A marked and rapid improvement in PsA and psoriatic skin lesions (Psoriasis Area Severity Index score 0; DAS28-CRP4 1.21; pain visual analog scale score 0) with concomitant clinical remission of hidradenitis suppurativa and pyoderma gangrenosum was observed after 4 weeks of treatment. The effect was durable over the 36 weeks of treatment, and adalimumab was well tolerated.Hidradenitis suppurativa is notoriously difficult to treat. Currently available therapeutic options including antibiotics (clindamycin-rifampin-tetracycline), isotretinoin, and dapsone. If antibiotics are ineffective, excisional surgery remains a valid therapeutic approach. In our case, hidradenitis suppurativa associated with PsA, acne, and pyoderma gangrenosum was successfully treated with adalimumab. Adalimumab was administered at the recommended dose for PsA therapy, leading to the resolution of the clinical symptoms of psoriasis and complete remission of hidradenitis suppurativa and pyoderma gangrenosum. Similar to the spectrum of recently described autoinflammatory syndromes, namely PASH (pyoderma gangrenosum, acne, and hidradenitis suppurativa), PAPA (pyogenic arthritis, acne, and pyoderma gangrenosum), and PAPASH (pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa), the concomitant diagnosis of PsA, pyoderma gangrenosum, acne, and hidradenitis suppurativa may represent a new syndrome; the acronym could be PsAPASH.4Hsiao J.L. Antaya R.J. Berger T. Maurer T. Shinkai K. Leslie K.S. Hidradenitis suppurativa and concomitant pyoderma gangrenosum: a case series and literature review.Arch Dermatol. 2010; 146: 1265-1270Crossref PubMed Scopus (88) Google Scholar, 5Marzano A.V. Trevisan V. Gattorno M. Ceccherini I. De Simone C. Crosti C. Pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH): a new autoinflammatory syndrome associated with a novel mutation of the PSTPIP1 gene.JAMA Dermatol. 2013; 149: 762-764Crossref PubMed Scopus (142) Google Scholar As shown in this case, TNF-alfa inhibition may represent a promising therapeutic strategy for treating multiple concomitant skin disorders, such as that with common pathogenic mechanisms. However, further clinical observations will be helpful to establish the prevalence of this clinical entity and its treatment. To the Editor: A 50-year-old man with refractory and multitherapy-resistant hidradenitis suppurativa was referred for evaluation after having been unsuccessfully treated with dapsone, oral isotretinoin, and several cycles of antibiotics (clindamycin-rifampin, tetracycline, cephalosporin) (Fig 1, A). He had hidradenitis suppurativa since the age of 43 years, was overweight and a heavy tobacco smoker, and had a medical history of acne, diabetes mellitus type 2, arterial hypertension, hypertriglyceridemia, hiatal hernia, depression, and psoriatic arthritis (PsA). Active acne pustules and comedonal lesions were observed on the face and neck; painful sterile abscesses and hypertrophic scars were present at the axillae and were classified as hidradenitis suppurativa Hurley II stage of severity. The patient had also erythematous scaly lesions on the scalp associated with severe joint and diffuse inflammation leading to the clinical diagnosis of PsA (Psoriasis Area Severity Index score 1.2; DAS28-CRP4 5.78; pain visual analog scale score 70). Two ulcerative lesions on his right leg had a dusky erythematous undermined edge (Fig 1, B), and were clinically and histologically diagnosed as pyoderma gangrenosum after the exclusion of diagnoses including neutrophilic disorders, vasculopathies, and infections. His quality of life was severely hampered by disability and social discomfort. Adalimumab is a highly specific tumor necrosis factor (TNF)-alfa inhibitor, binding to both soluble and membrane-bound TNF-alfa. TNF-alfa is a proinflammatory cytokine with a pathogenetic role in several immune-mediated diseases such as psoriasis, hidradenitis suppurativa, and pyoderma gangrenosum. The efficacy and safety of adalimumab in treating PsA is largely demonstrated, whereas limited evidence of its off-label use in treating hidradenitis suppurativa, pyoderma gangrenosum, or concomitant skin disorders has been reported.1Miller I. Lynggaard C.D. Lophaven S. Zachariae C. Dufour D.N. Jemec G.B. A double-blind placebo-controlled randomized trial of adalimumab in the treatment of hidradenitis suppurativa.Br J Dermatol. 2011; 165: 391-398Crossref PubMed Scopus (158) Google Scholar, 2Kimball A.B. Kerdel F. Adams D. et al.Adalimumab for the treatment of moderate to severe hidradenitis suppurativa: a parallel randomized trial.Ann Intern Med. 2012; 157: 846-855Crossref PubMed Scopus (311) Google Scholar, 3Reddick C.L. Singh M.N. Chalmers R.J. Successful treatment of superficial pyoderma gangrenosum associated with hidradenitis suppurativa with adalimumab.Dermatol Online J. 2010; 16: 15PubMed Google Scholar Randomized, double-blind, placebo-controlled studies have assessed the efficacy and safety of adalimumab therapy in patients affected by hidradenitis suppurativa.1Miller I. Lynggaard C.D. Lophaven S. Zachariae C. Dufour D.N. Jemec G.B. A double-blind placebo-controlled randomized trial of adalimumab in the treatment of hidradenitis suppurativa.Br J Dermatol. 2011; 165: 391-398Crossref PubMed Scopus (158) Google Scholar, 2Kimball A.B. Kerdel F. Adams D. et al.Adalimumab for the treatment of moderate to severe hidradenitis suppurativa: a parallel randomized trial.Ann Intern Med. 2012; 157: 846-855Crossref PubMed Scopus (311) Google Scholar Adalimumab therapy was initiated at a dose of 40 mg every other week. A marked and rapid improvement in PsA and psoriatic skin lesions (Psoriasis Area Severity Index score 0; DAS28-CRP4 1.21; pain visual analog scale score 0) with concomitant clinical remission of hidradenitis suppurativa and pyoderma gangrenosum was observed after 4 weeks of treatment. The effect was durable over the 36 weeks of treatment, and adalimumab was well tolerated. Hidradenitis suppurativa is notoriously difficult to treat. Currently available therapeutic options including antibiotics (clindamycin-rifampin-tetracycline), isotretinoin, and dapsone. If antibiotics are ineffective, excisional surgery remains a valid therapeutic approach. In our case, hidradenitis suppurativa associated with PsA, acne, and pyoderma gangrenosum was successfully treated with adalimumab. Adalimumab was administered at the recommended dose for PsA therapy, leading to the resolution of the clinical symptoms of psoriasis and complete remission of hidradenitis suppurativa and pyoderma gangrenosum. Similar to the spectrum of recently described autoinflammatory syndromes, namely PASH (pyoderma gangrenosum, acne, and hidradenitis suppurativa), PAPA (pyogenic arthritis, acne, and pyoderma gangrenosum), and PAPASH (pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa), the concomitant diagnosis of PsA, pyoderma gangrenosum, acne, and hidradenitis suppurativa may represent a new syndrome; the acronym could be PsAPASH.4Hsiao J.L. Antaya R.J. Berger T. Maurer T. Shinkai K. Leslie K.S. Hidradenitis suppurativa and concomitant pyoderma gangrenosum: a case series and literature review.Arch Dermatol. 2010; 146: 1265-1270Crossref PubMed Scopus (88) Google Scholar, 5Marzano A.V. Trevisan V. Gattorno M. Ceccherini I. De Simone C. Crosti C. Pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH): a new autoinflammatory syndrome associated with a novel mutation of the PSTPIP1 gene.JAMA Dermatol. 2013; 149: 762-764Crossref PubMed Scopus (142) Google Scholar As shown in this case, TNF-alfa inhibition may represent a promising therapeutic strategy for treating multiple concomitant skin disorders, such as that with common pathogenic mechanisms. However, further clinical observations will be helpful to establish the prevalence of this clinical entity and its treatment.