Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab

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Zouboulis" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": "Syndromic hidradenitis suppurativa (HS) is a form of symptom constellations, which differs from the familial and genetic form and comprises predominantly osteoarticular manifestations. Many forms include pyoderma gangrenosum and acne (PASH), pyogenic arthritis (PAPASH), spondyloarthritis (PASS) and psoriatic arthritis (PsAPASH) and are categorized in the autoinflammatory syndromes. Anti-TNF-α and anti-IL-1a blockade are between the therapeutic approaches that improve skin symptoms and prevent permanent osteoarticular damage. This case report refers to the successful treatment of a mixed phenotype of the aforementioned symptoms using the IL-17A inhibitor secukinumab after initial treatment with adalimumab. The therapy improved both cutaneous and reported osteoarticular symptoms. Different approaches for these recalcitrant HS syndromes are essential in order to achieve long-term remission for those patients." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/10-381", "name": "Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic..." } } ] } Home Browse Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Nikolakis G, Kreibich K, Vaiopoulos A et al. Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.12688/f1000research.52100.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Case Report Revised Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] Georgios Nikolakis 1,2 , Katja Kreibich 1 , Aristeidis Vaiopoulos 1,2 , [...] Katarzyna Kaleta 3 , Joud Talas 1 , Markus Becker 1 , Christos C. Zouboulis 1,2 Georgios Nikolakis 1,2 , Katja Kreibich 1 , [...] Aristeidis Vaiopoulos 1,2 , Katarzyna Kaleta 3 , Joud Talas 1 , Markus Becker 1 , Christos C. Zouboulis 1,2 PUBLISHED 16 Jul 2021 Author details Author details 1 Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Theodor Fontane Medical School, Dessau, 06847, Germany 2 European Hidradenitis Suppurativa Foundation, Dessau, 06847, Germany 3 Department of Dermatology, Jagiellonian University Medical College, Krakow, 31-008, Poland Georgios Nikolakis Roles: Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Katja Kreibich Roles: Investigation, Methodology, Resources, Writing – Review & Editing Aristeidis Vaiopoulos Roles: Supervision, Validation, Visualization, Writing – Review & Editing Katarzyna Kaleta Roles: Investigation, Methodology, Supervision, Validation, Writing – Review & Editing Joud Talas Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Markus Becker Roles: Validation, Visualization, Writing – Review & Editing Christos C. Zouboulis Roles: Conceptualization, Methodology, Project Administration, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Syndromic hidradenitis suppurativa (HS) is a form of symptom constellations, which differs from the familial and genetic form and comprises predominantly osteoarticular manifestations. Many forms include pyoderma gangrenosum and acne (PASH), pyogenic arthritis (PAPASH), spondyloarthritis (PASS) and psoriatic arthritis (PsAPASH) and are categorized in the autoinflammatory syndromes. Anti-TNF-α and anti-IL-1a blockade are between the therapeutic approaches that improve skin symptoms and prevent permanent osteoarticular damage. This case report refers to the successful treatment of a mixed phenotype of the aforementioned symptoms using the IL-17A inhibitor secukinumab after initial treatment with adalimumab. The therapy improved both cutaneous and reported osteoarticular symptoms. Different approaches for these recalcitrant HS syndromes are essential in order to achieve long-term remission for those patients. READ ALL READ LESS Keywords PASH, PAPASH, PASS, "hidradenitis suppurativa", SAPHO, PAPA, "acne inversa", hidradenitis, secukinumab, syndrome, arthritis, autoinflammatory, pustulosis Corresponding Author(s) Georgios Nikolakis ( [email protected] ) Close Corresponding author: Georgios Nikolakis Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2021 Nikolakis G et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Nikolakis G, Kreibich K, Vaiopoulos A et al. Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.12688/f1000research.52100.2 ) First published: 13 May 2021, 10 :381 ( https://doi.org/10.12688/f1000research.52100.1 ) Latest published: 16 Jul 2021, 10 :381 ( https://doi.org/10.12688/f1000research.52100.2 ) Revised Amendments from Version 1 We have included in our revised version the comments of the two reviewers, both experts in the field. We think that the pathognomonic bull's sign could direct the physicians towards the diagnosis of a SAPHO syndrome. The possibility of a paradoxical reaction explaining PG was also added according to the reviewer's comment and should always be addressed. Despite this, the exact phenotypic constellation is still not described up to date. The existing autoinflammatory syndromes described have sometimes only minor phenotypic differences and a search for osteoarticular manifestations was not always performed (PET-CT or bone scan), especially for non-symptomatic patients. Moreover, there is rising evidence on the genetic background of such cases. Unfortunately, we did not manage to detect any mutations of the nicastrin gene or other gamma secretase genes in our case. Moreover, the initial HS severity scores were added and the need for long-term follow up (both for cutaneous AND osteoarticular - silent - manifestations) has been highlighted. We would like to thank both reviewers for their comments, since they contributed to the improvement of the manuscript We have included in our revised version the comments of the two reviewers, both experts in the field. We think that the pathognomonic bull's sign could direct the physicians towards the diagnosis of a SAPHO syndrome. The possibility of a paradoxical reaction explaining PG was also added according to the reviewer's comment and should always be addressed. Despite this, the exact phenotypic constellation is still not described up to date. The existing autoinflammatory syndromes described have sometimes only minor phenotypic differences and a search for osteoarticular manifestations was not always performed (PET-CT or bone scan), especially for non-symptomatic patients. Moreover, there is rising evidence on the genetic background of such cases. Unfortunately, we did not manage to detect any mutations of the nicastrin gene or other gamma secretase genes in our case. Moreover, the initial HS severity scores were added and the need for long-term follow up (both for cutaneous AND osteoarticular - silent - manifestations) has been highlighted. We would like to thank both reviewers for their comments, since they contributed to the improvement of the manuscript See the authors' detailed response to the review by Mathilde Daxhelet See the authors' detailed response to the review by Simone Garcovich READ REVIEWER RESPONSES Introduction Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disorder of the terminal hair follicle characterized by the presence of nodules, abscesses, tunnels and extensive scarring in the apocrine gland-rich areas of the body. 1 Immune dysregulation has been implicated in HS, with a wide range of cytokines identified. Significant increase of proinflammatory cytokines IL-1β, TNF-α, IL-17 and the antiinflammatory cytokine IL-10 has been detected in lesional and perilesional skin. 2 , 3 Apart from sporadic cases, there is a genetic background for certain HS patients, correlating with mutations in the γ-secretase genes nicastrin, presenilin enhancer 2 and presenilin. 4 HS has been described in association with several clinical syndromes that include comorbid disorders, such as pyogenic arthritis (PA), pyoderma gangrenosum (PG), acne, ulcerative colitis (UC) and psoriatic arthritis. Such syndromes include the triad of PG, acne and HS (PASH) alone or in combination with PA (PAPASH) or psoriatic arthritis (PsAPASH). In addition, HS can also be a feature of other syndromes such as the SAPHO syndrome, 5 which appear recalcitrant to treatment, even after the use of various biologics, such as anti-TNF and anti-IL-1. Here we describe a patient with a novel phenotypic variant of the syndromes described, who responded to treatment with the IL-17A inhibitor secukinumab. Figure 1. palmar psoriasis before (1a) and after (1b) treatment with secukinumab over 4 months. Manifestations of HS localized in the inguinofemoral region before (1c) and after (1d) treatment. Pyoderma gangrenosum two months after adalimumab discontinuation (1e), clinical image 4 months after secukinumab treatment (1f) and post-prednisolone i.v pulse therapy (1g). Plantar pustulosis before (1h) and after secukinumab treatment (1i). Figure 2. Bone scan revealing a “bull’s head” sign-like radiopharmaceutical accumulation of the costoclavicular region (2a, red arrow) and of the wrist joints (2b). (2c): histopathologic evaluation of palmar pustular eruptions revealed characteristic microabscesses of subcorneal neutrophilic accumulation. (2d): Histology of the lower-leg ulcerations demonstrated diffuse neutrophilic inflammation as a hallmark of pyoderma gangrenosum. Case A 50-year-old female, Caucasian, unemployed patient was admitted to our departments suffering from HS. The patient reported a disease onset of 25 years, describing exacerbations with relapsing nodules, abscesses, and draining sinus tracts. Among the risk factors correlated with the disease, the patient was obese (BMI = 36) and a smoker (34-pack years). Moreover, she had a positive familial history, with her maternal grandmother having had severe refractory HS. Sequencing of the γ-secretase gene complex did not reveal any relevant mutations. The patient reported to having up to 10-15 stools daily. A colonoscopy was performed three years ago, which excluded inflammatory bowel disease. Twelve years after being diagnosed with HS, the patient developed acne conglobata (AC), which was treated without systemic therapy. In addition, she underwent numerous incisions and radical excisions, antibiotic treatment with doxycycline, and the combination of clindamycin and rifampicin over 3 months, according to the HS treatment guidelines, 1 , 2 without sustained remission of the lesions. A previous 1-year therapy with isotretinoin did not improve the HS lesions. The patient was included in a clinical trial combining weekly administration of 40 mg adalimumab s.c. vs. placebo for 3 months, followed by continuation of adalimumab treatment in the same dose over 15 months. After this period, the patient was lost to follow-up. She described an improvement of the HS lesions and reduction of flares under adalimumab. During this time, her general practitioner discontinued adalimumab treatment, judging that the treatment lacked efficacy. One month after discontinuation of adalimumab, the patient developed confluent erythematous pustules on the palms ( Figure 1a ) and soles ( Figure 1h ) with psoriasis-like scaling of the lesions followed by intermittent shoulders and knee pain and swelling. We performed a bone scan, which showed intense radiopharmaceutical accumulation of the left knee ( Figure 2a ) and the wrist joints showed signs of arthritis and synovitis ( Figure 2b ), with no typical pattern of psoriatic arthritis. The pattern of the bull’s head sign ( Figure 2a , red arrow) was detected, usually identified as a pathognomonic sign of SAPHO syndrome. 1 The patient did not admit having a pain or recurrent swelling of the costoclavicular region or back pains. No typical signs of osteitis were detected. Dermatohistology of the palmoplantar lesions revealed characteristic neutrophilic abscesses, compatible with pustular psoriasis ( Figure 2c ). Two months after therapy discontinuation, single, disseminated, painful pustules appeared on both thighs and lower legs ( Figure 1e ), which progressed to painful ulcers ( Figure 1f ) with elevated violaceous margins. The histopathological evaluation confirmed a PG ( Figure 2d ). Based on the disease pathophysiology, we initiated therapy with secukinumab 300 mg s.c weekly for the first month and then monthly thereafter. Before the initiation of treatment the patient was reported to have an IHS4 score of 17 and a DLQI score of 23. Four months later, the patient demonstrated a significant remission of her HS lesions ( Figure 1d ) (ΔIHS4 9 and ΔDLQI 11), joint pains and pustular psoriasis ( Figure 1b , Figure 1i ), with only moderate improvement of her PG lesions. An epithelization was not observed. The PG showed no improvement and 100 mg prednisolone daily i.v. over three days was added to the treatment, which was subsequently tapered over one month. The treatment was followed by PG improvement ( Figure 1g ). Discussion HS can also be a main or secondary element of certain syndromes highlighted through their unique phenotypes, 5 known as autoinflammatory diseases (AID). AID manifests with recurrent sterile inflammation, while high autoantibody serum levels or antigen-specific lymphocytes are lacking. 6 – 9 These syndromes combine dermatological manifestations (HS, PPP, AC, PG), musculoskeletal disorders (arthritis, synovitis, hyperostosis, osteitis) and gastroenterological manifestations (ulcerative colitis, M. Crohn). Combinations lead to already described syndromes such as PASH, 10 , 11 PASS, 8 PAPASH, 10 PsAPASH 12 and SAPHO. 13 These disorders are characterized by aberrant release of IL-1β, which mediates the increase of tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) and other chemokines, which are responsible for neutrophilic recruitment and might promote an anti-apoptotic microenvironment. 14 – 17 IL-17 also promotes neutrophilic recruitment and activation and has a synergistic effect with TNF-α. 18 An imbalance of the Th17/Treg lymphocyte ratio is believed to aggravate autoinflammation and was reported both in PG and HS independently. 19 , 20 Therapeutic combinations of TNF-α and IL-17 and/or IL-1β blocking agents might provide a solution for recalcitrant syndromic HS cases. 2 We describe a new syndromic HS-related phenotype (pustular Ps oriasis, A rthritis, P G, S ynovitis, A cne, S uppurative H idradenitis). The pathophysiology based on the dysregulation of IL-17 production provided the rationale for the treatment with the IL-17A inhibitor secukinumab. This unique phenotypic constellation could also be addressed as a variant of SAPHO syndrome. 3 Moreover, pustular lesions and PG could be explained as “paradoxical” reactions to the previous adalimumab treatment or its switch to a new biologic treatment. 4,5 Despite these promising results, long term follow-up for these patients and controlled clinical studies can determine if treatment with IL-17A inhibitors can result in long-term remission. 6 Moreover, this case underlines the role of the dermatologist in diagnosing such symptoms and leading a multidisciplinary approach for these patients. Dermatological manifestations can precede the osteoarticular or other organ symptoms and timely treatment initiation might avoid irreversible complications. Data availability All data underlying the results are available as part of the article and no additional source data are required. Consent The patient has provided written consent for the use of all photos provided in the manuscript. The consent included potential use of the material in lecture(s) and/or publication(s). References 1. Kundu BK, Naik AK, Bhargava S, et al. : Diagnosing the SAPHO syndrome: A report of three cases and review of literature. Clin Rheumatol. 2013; 32 : 1237–43. PubMed Abstract | Publisher Full Text 2. Nikolakis G, Kaleta KP, Vaiopoulos AG, et al. : Phenotypes and Pathophysiology of Syndromic Hidradenitis Suppurativa: Different Faces of the Same Disease? A Systematic Review.2020: 1–25. PubMed Abstract | Publisher Full Text 3. Van Doornum S, Barraclough D, McColl G, et al. : Sapho: Rare or just not recognized? Semin Arthritis Rheum. 2000; 30 : 70–7. PubMed Abstract | Publisher Full Text 4. Jin K, Matsuzaki Y, Akasaka E, et al. : Pyoderma gangrenosum triggered by switching from adalimumab to secukinumab. J Dermatol . 2019; 46 : e108–9. PubMed Abstract | Publisher Full Text 5. Tan Y, Kavaklieva S, Wood F: Pyoderma gangrenosum induced by adalimumab in a seropositive rheumatoid arthritis patient: a paradoxical effect of adalimumab? Rheumatology . 2021. PubMed Abstract | Publisher Full Text 6. Garcovich S, De Simone C, Berti E, et al. : Drug management of neutrophilic dermatoses. Expert Rev Clin Pharmacol . 2017; 10 : 1119–28. PubMed Abstract | Publisher Full Text 7. Ciccarelli F, Martinis M, Ginaldi L: An Update on Autoinflammatory Diseases. Curr Med Chem. 2013 Dec; 21 (3): 261–9. PubMed Abstract | Publisher Full Text | Free Full Text 8. Leuenberger M, Berner J, Di Lucca J, et al. : PASS Syndrome: An IL-1-Driven Autoinflammatory Disease. Dermatology. 2016 Apr; 232 (2): 254–8. PubMed Abstract | Publisher Full Text 9. Contassot E, Beer HD, French LE: Interleukin-1, inflammasomes, autoinflammation and the skin. Swiss Med Wkly. 2012 May; 142 (MAY): w13590. PubMed Abstract | Publisher Full Text 10. Sonbol H, Duchatelet S, Miskinyte S, et al. : PASH syndrome (pyoderma gangrenosum, acne and hidradenitis suppurativa): a disease with genetic heterogeneity. Br J Dermatol. 2018; 178 (1): e17–8. PubMed Abstract | Publisher Full Text 11. Braun-Falco M, Kovnerystyy O, Lohse P, et al. : Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)-a new autoinflammatory syndrome distinct from PAPA syndrome. J Am Acad Dermatol. 2012 Mar; 66 (3): 409–15. PubMed Abstract | Publisher Full Text 12. Saraceno R, Babino G, Chiricozzi A, et al. : A new syndrome associated with hidradenitis suppurativa with response to tumor necrosis factor inhibition. J Am. Dermatol. 2015; 72 : e42–4. PubMed Abstract | Publisher Full Text 13. Chamot AM, Benhamou CL, Kahn MF, et al. : Acne-pustulosis-hyperostosis-osteitis syndrome. Results of a national survey. 85 cases. Rev Rhum Mal Osteoartic. 1987; 54 (3): 187–96. PubMed Abstract 14. Marzano AV, Fanoni D, Antiga E, et al. : Expression of cytokines, chemokines and other effector molecules in two prototypic autoinflammatory skin diseases, pyoderma gangrenosum and Sweet’s syndrome. Clin Exp Immunol. 2014 Oct; 178 (1): 48–56. PubMed Abstract | Publisher Full Text | Free Full Text 15. Mankan AK, Dau T, Jenne D, et al. : The NLRP3/ASC/Caspase-1 axis regulates IL-1β processing in neutrophils. Eur J Immunol. 2012 Mar; 42 (3): 710–5. PubMed Abstract | Publisher Full Text 16. Guma M, Ronacher L, Liu-Bryan R, et al. : Caspase 1-independent activation of interleukin-1β in neutrophil-predominant inflammation. Arthritis Rheum. 2009 Dec; 60 (12): 3642–50. PubMed Abstract | Publisher Full Text | Free Full Text 17. Mitroulis I, Kourtzelis I, Kambas K, et al. : Regulation of the autophagic machinery in human neutrophils. Eur J Immunol. 2010 May; 40 (5): 1461–72. PubMed Abstract | Publisher Full Text 18. Donetti E, Cornaghi L, Gualerzi A, et al. : An innovative three-dimensional model of normal human skin to study the proinflammatory psoriatic effects of tumor necrosis factor-alpha and interleukin-17. Cytokine. 2014 Jul; 68 (1): 1–8. PubMed Abstract | Publisher Full Text 19. Moran B, Sweeney CM, Hughes R, et al. : Hidradenitis Suppurativa Is Characterized by Dysregulation of the Th17:Treg Cell Axis, Which Is Corrected by Anti-TNF Therapy. J Invest Dermatol. 2017 Nov; 137 (11): 2389–95. PubMed Abstract | Publisher Full Text 20. Negus D, Ahn C, Huang W: An update on the pathogenesis of hidradenitis suppurativa: implications for therapy. Expert Rev Clin Immunol. 2018 Apr; 14 (4): 275–83. PubMed Abstract | Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 13 May 2021 ADD YOUR COMMENT Comment Author details Author details 1 Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Theodor Fontane Medical School, Dessau, 06847, Germany 2 European Hidradenitis Suppurativa Foundation, Dessau, 06847, Germany 3 Department of Dermatology, Jagiellonian University Medical College, Krakow, 31-008, Poland Georgios Nikolakis Roles: Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Katja Kreibich Roles: Investigation, Methodology, Resources, Writing – Review & Editing Aristeidis Vaiopoulos Roles: Supervision, Validation, Visualization, Writing – Review & Editing Katarzyna Kaleta Roles: Investigation, Methodology, Supervision, Validation, Writing – Review & Editing Joud Talas Roles: Conceptualization, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Markus Becker Roles: Validation, Visualization, Writing – Review & Editing Christos C. Zouboulis Roles: Conceptualization, Methodology, Project Administration, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 16 Jul 2021, 10:381 https://doi.org/10.12688/f1000research.52100.2 version 1 Published: 13 May 2021, 10:381 https://doi.org/10.12688/f1000research.52100.1 Copyright © 2021 Nikolakis G et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Nikolakis G, Kreibich K, Vaiopoulos A et al. Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.12688/f1000research.52100.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 16 Jul 2021 Revised Views 0 Cite How to cite this report: Daxhelet M. Reviewer Report For: Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.5256/f1000research.57760.r89808 ) The direct URL for this report is: https://f1000research.com/articles/10-381/v2#referee-response-89808 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 07 Sep 2021 Mathilde Daxhelet , Department of Dermatology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium Approved VIEWS 0 https://doi.org/10.5256/f1000research.57760.r89808 I approve this ... Continue reading READ ALL I approve this article with no reservation. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Hidradenitis Suppurativa I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Daxhelet M. Reviewer Report For: Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.5256/f1000research.57760.r89808 ) The direct URL for this report is: https://f1000research.com/articles/10-381/v2#referee-response-89808 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Garcovich S. Reviewer Report For: Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.5256/f1000research.57760.r89809 ) The direct URL for this report is: https://f1000research.com/articles/10-381/v2#referee-response-89809 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 20 Jul 2021 Simone Garcovich , Department of Dermatology, Università Cattolica del Sacro Cuore, Rome, Italy Approved VIEWS 0 https://doi.org/10.5256/f1000research.57760.r89809 The authors have addressed all of the ... Continue reading READ ALL The authors have addressed all of the reviewers' comments and substantially improved the paper. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Hidradenitis suppurativa I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Garcovich S. Reviewer Report For: Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.5256/f1000research.57760.r89809 ) The direct URL for this report is: https://f1000research.com/articles/10-381/v2#referee-response-89809 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 13 May 2021 Views 0 Cite How to cite this report: Garcovich S. Reviewer Report For: Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.5256/f1000research.55330.r85308 ) The direct URL for this report is: https://f1000research.com/articles/10-381/v1#referee-response-85308 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 07 Jun 2021 Simone Garcovich , Department of Dermatology, Università Cattolica del Sacro Cuore, Rome, Italy Approved VIEWS 0 https://doi.org/10.5256/f1000research.55330.r85308 This is a very interesting report on a exemplary case of syndromic hidradenitis suppurativa, requiring a complex systemic treatment. While potentially interesting, there are some minor points to be addressed by the authors, to further improve an already well-written case ... Continue reading READ ALL This is a very interesting report on a exemplary case of syndromic hidradenitis suppurativa, requiring a complex systemic treatment. While potentially interesting, there are some minor points to be addressed by the authors, to further improve an already well-written case report: 1. Regarding joint manifestations: it seems there is some minor uptake of radiotracer localized to the sacroiliac joints. Osteoarticular involvement strongly reminds the SAPHO pattern. Did the patient refer any back pain? Differential diagnosis with SAPHO should be discussed by the authors. 2. The authors propose a novel acronym for the reported case. In my opinion, the conclusion section should be more conservative, as there is no experimental (genetic, molecular, cytokine data etc.) supporting this concept. Furthermore, this is a heavily pre-treated patient with a long disease history of HS. Could be there be an association between the previous exposure to multiple drugs (retinoids, anti-TNFs, etc.) and the development of "paradoxical" autoinflammatory extracutaneous involvement (such as recalcitrant PG)? This could be a more interesting take on the case? Please include some additional references. 3. Treatment: the authors should better describe the take-home messages for the therapeutic management of such complex/severe disease phenotypes. Maybe, a combination treatment strategy for complex autoinflammatory disease phenotypes is more effective than monotherapy (i.e. secukinumab alone)? Please include some additional references on this such as: Garcovich et al. (2017) 1 . Jin et al. (2019) 2 . Tan et al. (2021) 3 . Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Yes References 1. Garcovich S, De Simone C, Berti E, Marzano AV: Drug management of neutrophilic dermatoses. Expert Rev Clin Pharmacol . 2017; 10 (10): 1119-1128 PubMed Abstract | Publisher Full Text 2. Jin K, Matsuzaki Y, Akasaka E, Nakano H, et al.: Pyoderma gangrenosum triggered by switching from adalimumab to secukinumab. J Dermatol . 2019; 46 (3): e108-e109 PubMed Abstract | Publisher Full Text 3. Tan Y, Kavaklieva S, Wood F: Pyoderma gangrenosum induced by biosimilar adalimumab in a seropositive rheumatoid arthritis patient - a paradoxical effect of adalimumab?. Rheumatology (Oxford) . 2021. PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Hidradenitis suppurativa I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Garcovich S. Reviewer Report For: Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.5256/f1000research.55330.r85308 ) The direct URL for this report is: https://f1000research.com/articles/10-381/v1#referee-response-85308 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 16 Jul 2021 Nikolakis Georgios 16 Jul 2021 Author Response We would like to thank Dr. Garcovich for approving our manuscript, their careful evaluation of the case and their contribution to its improvement. The important differential diagnosis of the ... Continue reading We would like to thank Dr. Garcovich for approving our manuscript, their careful evaluation of the case and their contribution to its improvement. The important differential diagnosis of the case being a variant of SAPHO syndrome including HS and a paradoxical reaction to the switch of the biologic(s) or to the previous adalimumab treatment were also addressed. An extensive opinion on combination of treatments (IL17/TNFα) or IL-1β was included but because of the lack of controlled studies - as Dr Garcovich mentioned in their article - it cannot have a strong recommendation level. We would like to thank Dr. Garcovich for approving our manuscript, their careful evaluation of the case and their contribution to its improvement. The important differential diagnosis of the case being a variant of SAPHO syndrome including HS and a paradoxical reaction to the switch of the biologic(s) or to the previous adalimumab treatment were also addressed. An extensive opinion on combination of treatments (IL17/TNFα) or IL-1β was included but because of the lack of controlled studies - as Dr Garcovich mentioned in their article - it cannot have a strong recommendation level. Competing Interests: No competing interests Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 16 Jul 2021 Nikolakis Georgios 16 Jul 2021 Author Response We would like to thank Dr. Garcovich for approving our manuscript, their careful evaluation of the case and their contribution to its improvement. The important differential diagnosis of the ... Continue reading We would like to thank Dr. Garcovich for approving our manuscript, their careful evaluation of the case and their contribution to its improvement. The important differential diagnosis of the case being a variant of SAPHO syndrome including HS and a paradoxical reaction to the switch of the biologic(s) or to the previous adalimumab treatment were also addressed. An extensive opinion on combination of treatments (IL17/TNFα) or IL-1β was included but because of the lack of controlled studies - as Dr Garcovich mentioned in their article - it cannot have a strong recommendation level. We would like to thank Dr. Garcovich for approving our manuscript, their careful evaluation of the case and their contribution to its improvement. The important differential diagnosis of the case being a variant of SAPHO syndrome including HS and a paradoxical reaction to the switch of the biologic(s) or to the previous adalimumab treatment were also addressed. An extensive opinion on combination of treatments (IL17/TNFα) or IL-1β was included but because of the lack of controlled studies - as Dr Garcovich mentioned in their article - it cannot have a strong recommendation level. Competing Interests: No competing interests Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Daxhelet M. Reviewer Report For: Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.5256/f1000research.55330.r85309 ) The direct URL for this report is: https://f1000research.com/articles/10-381/v1#referee-response-85309 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 26 May 2021 Mathilde Daxhelet , Department of Dermatology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.55330.r85309 Thank you for giving me the opportunity to review this really interesting case. This case report describes an mixed syndrome encountered in a patient initially suffering from HS and treated with secukinumab. The clinical, ... Continue reading READ ALL Thank you for giving me the opportunity to review this really interesting case. This case report describes an mixed syndrome encountered in a patient initially suffering from HS and treated with secukinumab. The clinical, scintigraphic and histopathological images provided are of high quality. However I would like to add some details to the case description: The locations of the HS lesions on the patient's skin. Why is she unemployed? Because of HS? I would also add the initial severity assessment scores (IHS4 and DLQI) before secukinumab to better understand the improvement of symptoms with treatment. I would specify that the bull's head sign is typical of SAPHO syndrome to facilitate understanding of the case as not all doctors are experts in interpreting bone scans. Finally, I would add to the discussion that the initial response to secukinumab is promising but long-term follow-up of the patient is needed to assess long-term remission. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Hidradenitis Suppurativa I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Daxhelet M. Reviewer Report For: Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.5256/f1000research.55330.r85309 ) The direct URL for this report is: https://f1000research.com/articles/10-381/v1#referee-response-85309 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 16 Jul 2021 Nikolakis Georgios 16 Jul 2021 Author Response We would like to thank Dr. Daxhelet for their comments and their valuable contribution to improve the manuscript We have mentioned the initial HS scores. Unemployment was not correlated ... Continue reading We would like to thank Dr. Daxhelet for their comments and their valuable contribution to improve the manuscript We have mentioned the initial HS scores. Unemployment was not correlated with HS. The localization of the lesions was highlighted. We added the comment about the bull's head sign and its correlation with SAPHO syndrome. A sentence was added in the discussion, underlining the importance of long-term follow-up also in combination with the other reviewer's remarks We would like to thank Dr. Daxhelet for their comments and their valuable contribution to improve the manuscript We have mentioned the initial HS scores. Unemployment was not correlated with HS. The localization of the lesions was highlighted. We added the comment about the bull's head sign and its correlation with SAPHO syndrome. A sentence was added in the discussion, underlining the importance of long-term follow-up also in combination with the other reviewer's remarks Competing Interests: no competing interests Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 16 Jul 2021 Nikolakis Georgios 16 Jul 2021 Author Response We would like to thank Dr. Daxhelet for their comments and their valuable contribution to improve the manuscript We have mentioned the initial HS scores. Unemployment was not correlated ... Continue reading We would like to thank Dr. Daxhelet for their comments and their valuable contribution to improve the manuscript We have mentioned the initial HS scores. Unemployment was not correlated with HS. The localization of the lesions was highlighted. We added the comment about the bull's head sign and its correlation with SAPHO syndrome. A sentence was added in the discussion, underlining the importance of long-term follow-up also in combination with the other reviewer's remarks We would like to thank Dr. Daxhelet for their comments and their valuable contribution to improve the manuscript We have mentioned the initial HS scores. Unemployment was not correlated with HS. The localization of the lesions was highlighted. We added the comment about the bull's head sign and its correlation with SAPHO syndrome. A sentence was added in the discussion, underlining the importance of long-term follow-up also in combination with the other reviewer's remarks Competing Interests: no competing interests Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 13 May 2021 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 2 (revision) 16 Jul 21 read read Version 1 13 May 21 read read Mathilde Daxhelet , Université Libre de Bruxelles, Brussels, Belgium Simone Garcovich , Università Cattolica del Sacro Cuore, Rome, Italy Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2021 Daxhelet M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 07 Sep 2021 | for Version 2 Mathilde Daxhelet , Department of Dermatology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium 0 Views copyright © 2021 Daxhelet M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I approve this article with no reservation. Competing Interests No competing interests were disclosed. Reviewer Expertise Hidradenitis Suppurativa I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Daxhelet M. Peer Review Report For: Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.5256/f1000research.57760.r89808) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/10-381/v2#referee-response-89808 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2021 Garcovich S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 20 Jul 2021 | for Version 2 Simone Garcovich , Department of Dermatology, Università Cattolica del Sacro Cuore, Rome, Italy 0 Views copyright © 2021 Garcovich S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors have addressed all of the reviewers' comments and substantially improved the paper. Competing Interests No competing interests were disclosed. Reviewer Expertise Hidradenitis suppurativa I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Garcovich S. Peer Review Report For: Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.5256/f1000research.57760.r89809) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/10-381/v2#referee-response-89809 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2021 Garcovich S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 07 Jun 2021 | for Version 1 Simone Garcovich , Department of Dermatology, Università Cattolica del Sacro Cuore, Rome, Italy 0 Views copyright © 2021 Garcovich S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This is a very interesting report on a exemplary case of syndromic hidradenitis suppurativa, requiring a complex systemic treatment. While potentially interesting, there are some minor points to be addressed by the authors, to further improve an already well-written case report: 1. Regarding joint manifestations: it seems there is some minor uptake of radiotracer localized to the sacroiliac joints. Osteoarticular involvement strongly reminds the SAPHO pattern. Did the patient refer any back pain? Differential diagnosis with SAPHO should be discussed by the authors. 2. The authors propose a novel acronym for the reported case. In my opinion, the conclusion section should be more conservative, as there is no experimental (genetic, molecular, cytokine data etc.) supporting this concept. Furthermore, this is a heavily pre-treated patient with a long disease history of HS. Could be there be an association between the previous exposure to multiple drugs (retinoids, anti-TNFs, etc.) and the development of "paradoxical" autoinflammatory extracutaneous involvement (such as recalcitrant PG)? This could be a more interesting take on the case? Please include some additional references. 3. Treatment: the authors should better describe the take-home messages for the therapeutic management of such complex/severe disease phenotypes. Maybe, a combination treatment strategy for complex autoinflammatory disease phenotypes is more effective than monotherapy (i.e. secukinumab alone)? Please include some additional references on this such as: Garcovich et al. (2017) 1 . Jin et al. (2019) 2 . Tan et al. (2021) 3 . Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Yes References 1. Garcovich S, De Simone C, Berti E, Marzano AV: Drug management of neutrophilic dermatoses. Expert Rev Clin Pharmacol . 2017; 10 (10): 1119-1128 PubMed Abstract | Publisher Full Text 2. Jin K, Matsuzaki Y, Akasaka E, Nakano H, et al.: Pyoderma gangrenosum triggered by switching from adalimumab to secukinumab. J Dermatol . 2019; 46 (3): e108-e109 PubMed Abstract | Publisher Full Text 3. Tan Y, Kavaklieva S, Wood F: Pyoderma gangrenosum induced by biosimilar adalimumab in a seropositive rheumatoid arthritis patient - a paradoxical effect of adalimumab?. Rheumatology (Oxford) . 2021. PubMed Abstract | Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Hidradenitis suppurativa I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (1) Author Response 16 Jul 2021 Nikolakis Georgios We would like to thank Dr. Garcovich for approving our manuscript, their careful evaluation of the case and their contribution to its improvement. The important differential diagnosis of the case being a variant of SAPHO syndrome including HS and a paradoxical reaction to the switch of the biologic(s) or to the previous adalimumab treatment were also addressed. An extensive opinion on combination of treatments (IL17/TNFα) or IL-1β was included but because of the lack of controlled studies - as Dr Garcovich mentioned in their article - it cannot have a strong recommendation level. View more View less Competing Interests No competing interests reply Respond Report a concern Garcovich S. Peer Review Report For: Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.5256/f1000research.55330.r85308) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/10-381/v1#referee-response-85308 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2021 Daxhelet M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 26 May 2021 | for Version 1 Mathilde Daxhelet , Department of Dermatology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium 0 Views copyright © 2021 Daxhelet M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Thank you for giving me the opportunity to review this really interesting case. This case report describes an mixed syndrome encountered in a patient initially suffering from HS and treated with secukinumab. The clinical, scintigraphic and histopathological images provided are of high quality. However I would like to add some details to the case description: The locations of the HS lesions on the patient's skin. Why is she unemployed? Because of HS? I would also add the initial severity assessment scores (IHS4 and DLQI) before secukinumab to better understand the improvement of symptoms with treatment. I would specify that the bull's head sign is typical of SAPHO syndrome to facilitate understanding of the case as not all doctors are experts in interpreting bone scans. Finally, I would add to the discussion that the initial response to secukinumab is promising but long-term follow-up of the patient is needed to assess long-term remission. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Hidradenitis Suppurativa I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 16 Jul 2021 Nikolakis Georgios We would like to thank Dr. Daxhelet for their comments and their valuable contribution to improve the manuscript We have mentioned the initial HS scores. Unemployment was not correlated with HS. The localization of the lesions was highlighted. We added the comment about the bull's head sign and its correlation with SAPHO syndrome. A sentence was added in the discussion, underlining the importance of long-term follow-up also in combination with the other reviewer's remarks View more View less Competing Interests no competing interests reply Respond Report a concern Daxhelet M. Peer Review Report For: Case Report: PsAPSASH syndrome: an alternative phenotype of syndromic hidradenitis suppurativa treated with the IL-17A inhibitor secukinumab [version 2; peer review: 2 approved] . F1000Research 2021, 10 :381 ( https://doi.org/10.5256/f1000research.55330.r85309) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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