Case report: Treating a co-existence of hidradenitis suppurativa and psoriasis with different therapeutic approaches

Hidradenitis suppurativa and psoriasis are considered chronic inflammatory diseases suggesting the existence of common pathogenetic pathways. We present two cases of comorbid psoriasis and hidradenitis suppurativa, treated with certolizumab pegol and brodalumab due to failure of response to other conventional therapies. Monoclonal antibody therapies have revolutionized the treatment of chronic inflammatory disorders such as psoriasis and hidradenitis suppurativa. Given the good clinical response to anti-IL-17 and anti-tumor necrosis factor agents in patients undergoing psoriasis and hidradenitis treatment, investigations on this direction could represent the starting point in new therapeutic approach for revolutionary treatment in these difficult-to-treat diseases.


Introduction
Hidradenitis suppurativa (HS) and psoriasis are considered chronic inflammatory diseases suggesting the existence of common pathogenetic links [1][2][3] . Patients with psoriasis and HS have elevated levels of tumor necrosis factor (TNF) and interleukin-17 (IL-17) in lesional and non lesional tissues, which has been the justification for selective targeting of these inflammatory pathways 4-7 . We present two cases of co-existence of psoriasis and HS treated with certolizumab pegol and brodalumab due to the peculiarities of treatment with other therapies.

Case report
The first patient, a 27-year-old Caucasian woman, presented with extensive psoriasis vulgaris covering her head, trunk, lower limbs over a period of 5 years, with a recent PASI (Psoriasis Area Severity Index) score of 10.5 and 10% BSA (Body Surface Area) score. She, also, suffered from psoriatic arthritis with axial joint involvement (manifestations of hierolagonitis) over the previous 2 years and moderate HS of Hurley II stage disease on the axillae over the last year, with IHS4 (International Hidradenitis Suppurativa Severity Scoring System) score 10 (Figure 1a, b, c, d, e). Despite the limited extent of the lesions, the patient presented considerable pain, discomfort and substantial negative effect on quality of life. Patient's DLQI (Dermatology Life Quality Index) score was, also very high, 21. The patient didn't have a positive family history for the above diseases and the molecular control for HLA-B27 was negative. Previous treatments with topical corticosteroids and methotrexate for one year were not effective and treatment with apremilast for 8 months didn't offer clinical improvement in both diseases. The patient underwent comprehensive laboratory investigations, including complete blood cell count, chemistry panel, tuberculosis (Quantiferon-TB Gold test), human immunodeficiency virus and hepatitis B and C screening and chest x-ray. Since all these examinations revealed values within normal limits and because of the patient's desire for childbirth, she was treated with certolizumab pegol (CZP). The initial dose was 400mg, followed by 400mg every 2 weeks. Treatment with CZP significantly improved psoriasis and psoriatic arthritis at week 8 and HS at week 12. The PASI score after treatment was 1, BSA was 2%, whereas IHS4 score was 1. Except the clinical improvement, the DLQI score was impressively reduced to 2. (Figure 1f-i). She continues treatment 9 months after and at 3 months follow-up is fully controlled.

Amendments from Version 1
In the revised version of our manuscript, we changed the title to "Treating co-existence of hidradenitis suppurativa and psoriasis", instead of the term combination.
Also, we provide severity assessment before and after treatment for psoriasis and hidradenitis, for both cases. The clinical improvement is estimated using the PASI (Psoriasis Area Severity Index) score, BSA (Body Surface Area), and IHS4 (International Hidradenitis Suppurativa Severity Scoring System) score, while the impact on the quality of life is estimated with the DLQI (Dermatology Life Quality Index) score.

REVISED
The second patient, a 42-year-old Caucasian man, was referred to our hospital's dermatological department with multiple, itchy, scaly, red-gray psoriatic plaques covering almost all his body: scalp, arms, trunk, thighs (Figure 2a-d) for the previous 6 months, over a history of 10 years psoriatic disease (recent PASI: 18.5, BSA: 45%). The patient, also, experienced concomitant psoriatic arthritis with peripheral joint involvement and dactylitis discomfort over the previous 10 years, and moderate HS of Hurley II stage disease appearing on the groin area in the previous year. The IHS4 score was 10. The above diseases had a negative impact factor on his quality of life with DLQI 25. The patient's family history was positive: his mother and sister were also suffering from psoriasis. The patient had until recently received almost all the available therapies related to his diseases: cyclosporine for 2 years interrupted due to urea and creatinin increase (examinations restored after discontinuation), methotrexate and golimumab for 3 years with improvement only in psoriatic arthritis, adalimumab ustekinumab and secukinumab, with a partial response. After a complete laboratory examination, with results in normal limits, the patient started therapy with brodalumab. The initial dose was 210 mg at weeks 0, 1, 2 followed by 210 mg every 2 weeks. His psoriasis and psoriatic arthritis were highly improved at week 8 (Figure 2 e-h), as was HS at week 16. The PASI score after treatment was 1.5, the BSA was 8%, while IHS4 score was reduced to 3. He has continued treatment for 1 year; at 3 months follow-up he reported improvement in his quality of life and the DLQI score was 1.

Discussion
Monoclonal antibody therapies have revolutionized the treatment of chronic inflammatory disorders such as psoriasis and HS. CZP is a TNF inhibitor that does not have a fragment crystallizable (Fc) region, which is normally present in a complete antibody and therefore it does not cause antibody-dependent cellmediated cytotoxicity [8][9][10] . In contrast to other whole-antibody anti-TNFs, CZP crosses the placenta only by passive diffusion and could therefore be considered as the first-line choice of treatment for women who wish to become pregnant. Since CZP is an anti-TNF drug, therapies which have good clinical Brodalumab is a monoclonal antibody against human IL-17 receptor A (IL-17RA). Given its efficacy in psoriasis and its mechanism of action in psoriatic arthritis and HS, due to the patient's non response to all the available treatment options it was decided its use on the above combination diseases 11-14 .
It is well known that psoriasis and HS likely share immunopathogenetic pathways, including involvement of IL-17 and TNF. Given the good clinical response to anti-IL 17 and anti-TNF drugs in psoriasis and HS treatment, investigations into this direction could represent a starting point for a new therapeutic approach for revolutionary treatment of two difficult to treat diseases.

Data availability
All data underlying the results are available as part of the article and no additional source data are required.

Consent
Written informed consent for publication of their clinical details and clinical images was obtained from the patients.

Open Peer Review expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
I have prepared a PDF file with most of the points I think need to be addressed in order to make this case acceptable for indexing -please find the file here. For the second case we have really no proof, even a single photo, showing that brodalumab led to improvement of HS. Both Psoriasis and HS need to be assessed using both descriptive terms but also objective and validated scoring systems, to quantify the improvement.
Moreover, the improvement of HS under certolizumab pegol is not clear for me, since I cannot tell that inflammatory lesions (nodules, abscesses or sinus tracts) have decreased after therapy.
Since I believe that this case report can add to the current literature, opening ways for more antiinflammatory treatments for HS, I think that updating the documentation accordingly and providing some proof for the improvement of HS will make the manuscript acceptable for indexing.

Is the background of the cases' history and progression described in sufficient detail? © 2019 Tzellos T. 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.

Thrasyvoulos Tzellos
Department of Clinical Medicine, University of Tromsø, Tromsø, Norway I suggest changing the title to: "Treating co-existence of hidradenitis suppurativa and psoriasis" Introduction: Please change "We present two cases of comorbidity of psoriasis and HS" to "We present two cases of co-existence of psoriasis and HS". ○ For case report 1: Please provide a severity assessment for psoriasis.

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The authors only refer to "extensive". It would be important to report PASI or another measure of severity assessment.

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For case report 2: Please provide a severity assessment for psoriasis as for case 1.  We revised our manuscript according to your comments. All your comments were taken into account and please find below the answers: We changed the title according to your suggestion.

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In the introduction section, we changed the term comorbidity with the term coexistence.
○ Finally, we provide severity assessment before and after treatment for both psoriasis and hidradenitis, as well as DLQI score for the impact on the quality of life. In recent years, experimental and clinical evidence has accumulated that certain pathophysiological relationships exist between acne inversa and psoriasis. Therefore, it seems logical to treat the two diseases with a TNF inhibitor or an IL-17 receptor inhibitor if they are both present in individual cases. The therapeutic response reported here underlines the pathophysiological relationships mentioned on the one hand and is of interest for the treatment of selected patients on the other hand. The case reports presented here are therefore a valuable contribution.