Real-world adalimumab survival and discontinuation factors in hidradenitis suppurativa.

BACKGROUND AND OBJECTIVES: Survival analyses can provide valuable insights into effectiveness and safety as perceived by prescribers. Here, we aimed to evaluate adalimumab (ADA) survival and the interruption risk factors in a multicentre cohort of patients with hidradenitis suppurativa (HS). Moreover, we performed a subanalysis considering the periods before and after the onset of the COVID-19 pandemic. METHODS: We conducted a retrospective study including 539 adult patients with HS who received ADA from 1 May 2015 to 31 December 2022. Overall drug survival was analysed using Kaplan-Meier survival curves and compared between the subgroups via stratified log-rank test. Possible predictors for overall drug survival and reasons for discontinuation were assessed using univariate and multivariate Cox regression. RESULTS: Overall, 50.1% were females with a mean age of 43.5 ± 1 years and a mean BMI of 29.5 ± 6.7. At the start of ADA, 95.29% were biologic-naïve and 24.63% had undergone surgical treatment. During follow-up, 9.46% of patients required dose escalation, while 39.92% interrupted ADA. Concomitant therapy was used in 64.89% of cases. A subanalyses comparing pre- and post-pandemic periods revealed a tendency to initiate ADA treatment at a younger age, among patient with higher BMI and at a lower HS stage after COVID-19 pandemic. Interestingly, ADA demonstrated extended survival compared to previous studies, with a median overall drug survival of 56.2 months (95% CI 51.2 to 80.3). The primary causes for discontinuation were inefficacy (51.69%), followed by adverse effects (21.35%). Female sex, longer delay in HS diagnosis, higher baseline IHS4 score and concomitant spondyloarthritis were associated with poorer ADA survival or increased risk of discontinuation. CONCLUSIONS: ADA demonstrated prolonged survival (median 56.2 months). While addition of antibiotics did not have a positive effect on survival rate, basal IHS4 proved useful in predicting ADA survival.

Can Ultrasound Examinations Generate Pain in Hidradenitis Suppurativa Patients? Results from a Multicentric Cross-Sectional Study.

BACKGROUND: Pain is not a trivial issue for hidradenitis suppurativa (HS) patients and has been considered a domain in the Core Outcome Set. To date, there is no evidence about pain caused by the ultrasound examinations. OBJECTIVE: The aim of the study was to assess the presence of pain generated by the ultrasound examinations of HS patients. METHODS: A multicentric cross-sectional study for detecting pain during the ultrasound examinations of HS patients using a validated verbal questionnaire immediately after the imaging studies. Statistical analysis included demographic data and possible associations with sex, age, location, clinical (Hurley), and ultrasonographic scoring (SOS-HS). The statistical tests were two proportions Z test, χ2 test, Student's t test, and ANOVA. A p < 0.05 was considered significant. RESULTS: 317 patients met the criteria. 77.3% of them did not present pain. Of cases with pain, 59.8% were mild, 16.7% moderate, and 23.6% severe. No significant association was found with sex, age, staging, location, or the number of affected regions. Although nonsignificant, severe pain cases were more frequent in the clinical Hurley III and ultrasonographic SOS-HS III stages. CONCLUSION: Pain generated by the ultrasound examination of HS patients is infrequent.

External Validation of the IHS4-55 in a European Antibiotic-Treated Hidradenitis Suppurativa Cohort.

BACKGROUND: Previously, a new dichotomous outcome was developed, calculated as 55% reduction in the International Hidradenitis Suppurativa 4 (IHS4-55) score. It was validated in datasets of adalimumab and placebo-treated HS patients. External validation is an important aspect of clinical outcomes. OBJECTIVES: We aimed to externally validate the novel dichotomous IHS4-55 in a non-biologic treated dataset of HS patients. METHODS: Data from a previously published European-wide prospective clinical study of antibiotic treatment of HS patients were used to assess the association of IHS4-55 achievement with individual reduction in inflammatory nodules, abscesses, and draining tunnels. Moreover, the associations between IHS4-55 positivity and achievement of the minimal clinically important differences (MCIDs) for Dermatology Life Quality Index (DLQI), Numerical Rating Scale (NRS) Pain, and NRS Pruritus were analyzed. RESULTS: Data were obtained from 283 individual patients, of which 36.4% (103/283) were treated with clindamycin and rifampicin and 63.6% (180/283) with tetracyclines for 12 weeks. Achievers of the IHS4-55 demonstrated a significant reduction the counts of inflammatory nodules, abscesses, and draining tunnels (all p < 0.001). Additionally, IHS4-55 achievers had an odds ratio for achieving the MCID of DLQI, NRS Pain, and NRS Pruritus of 2.16 (95% CI 1.28-3.65, p < 0.01), 1.79 (95% CI 1.10-2.91, p < 0.05), and 1.95 (95% CI 1.18-3.22, p < 0.01), respectively. CONCLUSIONS: This study shows the external validity of the novel IHS4-55 by demonstrating a significant association between IHS4-55 achievement and a reduction in inflammatory lesion counts as well as achievement of MCIDs for DLQI, NRS Pain, and NRS Pruritus in an antibiotic-treated cohort. These findings support the use of the IHS4-55 as a novel primary outcome measure in clinical trials.

Pilonidal Sinus Disease is Associated with Severe Hidradenitis Suppurativa in a Spanish Cohort.

Hidradenitis suppurativa is a chronic inflammatory disorder of the hair follicle with a high level of morbidity. Pilonidal sinus disease is a comorbid disorder and may be the reason for first contact with the healthcare system of patients with hidradenitis suppurativa. The aim of this study was to evaluate the frequency of association of pilonidal sinus disease and hidradenitis suppurativa and to explore whether pilonidal sinus disease defines a different clinical profile for patients with hidradenitis suppurativa. A cross-sectional study in which data regarding past history of pilonidal sinus disease, clinical and sociodemographic information were recorded during the first visit to the Hidradenitis Suppurativa Clinic of 2 tertiary hospitals. A total of 839 patients were included in the study. Of these, 51.7% (434/839) were male and mean age was 37.3 ± 13.6 years. Pilonidal sinus disease was present in 32.6% (269/839) of the patients and was associated with an early debut of hidradenitis suppurativa, a higher Hurley stage, inflammatory phenotype and a greater number of fistulas and perianal involvement. Elapsed time between pilonidal sinus disease and diagnosis of hidradenitis suppurativa was associated with higher disease severity. Pilonidal sinus disease is a frequent comorbidity and risk marker for hidradenitis suppurativa disease severity. Pilonidal sinus disease could be a sentinel event to identify patients who would benefit from close treatment and follow-up.

Ultrasound-guided photodynamic therapy with intralesional methylene blue and a 635 nm light-emitting diode lamp in hidradenitis suppurativa: A retrospective study of 41 patients.

BACKGROUND: Photodynamic therapy for hidradenitis suppurativa (HS) is a therapeutic alternative with a good safety profile, but its effectiveness has yet to be demonstrated. OBJECTIVES: To demonstrate the effectiveness of PDT with intralesional methylene blue in HS lesions. METHODS: A retrospective cross-sectional study was performed. Forty-one patients were treated with intralesional methylene blue and a diode lamp. Follow-up was carried out at 1 and 6 months after therapy. Efficacy was determined by the diameter reduction of the lesion measured by high-frequency ultrasound. RESULTS: A reduction of ≥75% in the maximum diameter was recorded in 58.5% of the lesions, while 22% showed a reduction between 50% and 75%, and 19.5% showed a reduction of <50%. Recurrence rate was 12.5%. The lesions treated in patients with typical forms of HS (Canoui-Poitrine phenotype I) had a better therapeutic response. No statistically significant differences were found in terms of lesion location or concomitant treatment. CONCLUSION: This therapy may potentially be a cost-effective and well-tolerated local therapy for Hurley I-II patients with superficial abscesses and fistulas.

Multicentric Study on High-Frequency Ultrasound Characterization of Calcium Deposits in Dermal and Subcutaneous Calciphylaxis and Calcinosis.

OBJECTIVES: Calcium depositions are frequent in multiple inflammatory dermatosis, they can be explored by ultrasound (US) but the patterns of these depositions have not yet been described. The aim of this study is to describe different patterns of calcium deposition in inflammatory dermatoses. METHODS: The clinical and US data of 58 patients from 7 different centers with inflammatory dermatosis showing ultrasonography-detected calcium depositions was retrospectively reviewed. RESULTS: Dystrophic calcinosis represented 86.2%, calciphylaxis 8.6%, and metastatic calcinosis 5.2%. Three different sonographic patterns of calcium deposition were found: 1) thin hyperechoic bands, parallel to the surface of the epidermis, generating a strong and wide posterior acoustic shadow; 2) hyperechoic spots or lumps with a narrow acoustic shadow; and 3) a linear hyperechoic band parallel to the walls of a blood vessel with also a narrow acoustic shadow. The predominant pattern in metastatic calcifications was type 1, in dystrophic calcifications type 2, and in calciphylaxis type 3. In dystrophic calcinosis, cutis deposits were longer and wider than in calciphylaxis (P < .05). CONCLUSION: New data on inflammatory dermatoses with calcium deposition may be useful for the diagnosis and monitoring of calcium deposits and could avoid the performance of more invasive tests, such as a skin biopsy.

The efficacy and tolerability of tetracyclines and clindamycin plus rifampicin for the treatment of hidradenitis suppurativa: Results of a prospective European cohort study.

BACKGROUND: Tetracyclines and clindamycin plus rifampicin combination therapy are both considered first-line therapy in current hidradenitis suppurativa guidelines. However, evidence for their efficacy is drawn from small studies, often without validated outcomes. OBJECTIVE: To assess the 12-week efficacy of oral tetracyclines and a combination of clindamycin and rifampicin. METHODS: A prospective, international cohort study performed between October 2018 and August 2019. RESULTS: In total, 63.6% of the included 283 patients received oral tetracyclines, and 36.4% were treated with clindamycin and rifampicin. Both groups showed a significant decrease in International Hidradenitis Suppurativa Severity Score System from baseline (both P < .001). The Hidradenitis Suppurativa Clinical Response (HiSCR) was achieved in 40.1% and 48.2% of patients, respectively (P = .26). Patient characteristics or disease severity were not associated with the attainment of HiSCR or the minimal clinically important differences for the Dermatology Life Quality Index and pain. LIMITATIONS: Cohort study. Respectively, 23.9% and 19.4% of patients had to be excluded from the HiSCR analysis for the tetracycline and combination therapy group because of a low abscess and nodule count at baseline. CONCLUSION: This study shows significant efficacy of both tetracycline treatment and clindamycin and rifampicin combination therapy after 12 weeks in patients with hidradenitis suppurativa. No significant differences in efficacy were observed between the 2 treatments, regardless of disease severity.

Dapsone in hidradenitis suppurativa: A case series of 56 patients.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a challenging treatment. Current guidelines reserve dapsone as a third line agent for patients with mild to moderate HS. To our knowledge, only four small case series have been reported. The objective of this study was to assess the effectiveness and safety of dapsone in our clinical practice. A retrospective observational single-center study of 56 HS patients who underwent treatment with dapsone from May 1, 2015, to June 1, 2021, was performed. The Hidradenitis Suppurativa Clinical Response (HiSCR) scale was used to evaluate the response to treatment. Fifty-six patients were included, 66% of which were men, with a median age of 33 years. Most of them had mild or moderate disease and belonged to LC2 follicular phenotype. All patients had been refractory to first-line treatments. Dapsone was prescribed at doses of 50-150 mg/day. 62.5% of the patients achieved HiSCR after 12 weeks of treatment. No serious adverse reactions were detected. The median duration of treatment was 8 months. After multivariate analysis, an association was found between the presence of fistulous tracts and the risk of non-response to the drug. In four of the dapsone responders, oral retinoids were added to achieve a sustained response. Limitations include the retrospective and non-controlled nature of this study. In conclusion, dapsone is an effective and well-tolerated option for long-term HS treatment, and in this series, it was mainly chosen for patients with LC2 phenotype. It would be interesting to study combination with retinoids and other management options.

Hidradenitis Suppurativa: Proposal of Classification in Two Endotypes with Two-Step Cluster Analysis.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent disorder of the pilosebaceous unit. Currently, several attempts have been made to classify this disease according to its pathogenesis and clinical manifestations. We attempted at classifying 103 patients using two-step cluster analysis. METHODS: The final model included body mass index, C-reactive protein (CRP), and serum concentrations of IL-1, IL-6, IL-17, and IL-10 as continuous variables, and sex, later/early onset, anterior/posterior lesion sites, presence/absence of sinus tracts, nodules and abscesses, positive/negative history of pilonidal sinus, and presence/absence of mutations in gamma-secretase subunits (APH1A, APH1B, MEFV, NCSTN, PSEN1, PSEN2, PSENEN, PSTPIP1) as qualitative variables. RESULTS: The resultant model defined two groupings or clusters: cluster 1 (64.9% of patients) characterized by nonobese males, with nodular lesions in posterior sites, early-onset HS, higher IL-10, presence of gamma-secretase mutations, and history of pilonidal sinus; and cluster 2 (35.1% of patients) characterized by obese females or males, with lesions in anterior sites, more presence of sinus tracts and abscesses and less nodules, later-onset HS, and higher concentrations of IL-1, CRP, IL-17, and IL-6. Severity measures (Hurley, HS-PGA, and IHS4) and tobacco use were discarded because the analysis found them to be less relevant for clustering. CONCLUSION: Our resultant model confirms the clinical impression that HS is a disease spectrum with two pathogenic poles defining two clusters or endotypes. The probability of having severe disease was equally distributed in the two clusters. The variable with the highest predictive value for clustering was involvement of typical anterior sites (axillae, submammary) or atypical posterior sites (back, gluteal). Serum concentrations of interleukins, tobacco use, and sex had a lower predictive power for clustering.

Ultrasonographic Patterns of Cutaneous Sarcoidosis.

Sarcoidosis is a multiorgan disease characterized by the formation of noncaseating granulomas and possible skin involvement. Cutaneous sarcoidosis (CS) can be explored by ultrasonography when deep dermal or subcutaneous nodules are the clinical presentation. We reviewed the ultrasound characteristics of 14 patients (86% female; mean age, 55 years) with CS. Ultrasonography revealed dermal or subcutaneous hypoechoic areas with increased echogenicity and hypervascularity of the neighboring subcutaneous tissue. In 42.9% of cases a cobblestone pattern of the subcutaneous tissue suggestive of septal involvement was detected. These US features can support the detection of dermal and subcutaneous abnormalities in CS and its early diagnosis.

Maculopapular eruptions associated to COVID-19: A subanalysis of the COVID-Piel study.

A previous study has defined the maculopapular subtype of manifestations of COVID-19. The objective of our study was to describe and classify maculopapular eruptions associated with COVI-19. We carried out a subanalysis of the maculopapular cases found in the previous cross-sectional study. Using a consensus, we defined seven clinical patterns. We described patient demographics, the therapy received by the patient and the characteristics of each pattern. Consensus lead to the description of seven major maculopapular patterns: morbilliform (45.5%), other maculopapular (20.0%), purpuric (14.2%), erythema multiforme-like (9.7%), pytiriasis rosea-like (5.7%), erythema elevatum diutinum-like (2.3%), and perifollicular (2.3%). In most cases, maculopapular eruptions were coincident (61.9%) or subsequent (34.1%) to the onset of other COVID-19 manifestations. The most frequent were cough (76%), dyspnea (72%), fever (88%), and astenia (62%). Hospital admission due to pneumonia was frequent (61%). Drug intake was frequent (78%). Laboratory alterations associated with maculo-papular eruptions were high C-reactive protein, high D-Dimer, lymphopenia, high ferritin, high LDH, and high IL-6. The main limitation of our study was the impossibility to define the cause-effect relationship of each pattern. In conclusion, we provide a description of the cutaneous maculopapular manifestations associated with COVID-19. The cutaneous manifestations of COVID-19 are wide-ranging and can mimic other dermatoses.

Ustekinumab with Intravenous Infusion: Results in Hidradenitis Suppurativa.

Adalimumab is the only approved biological therapy for hidradenitis suppurativa (HS). The last published recommendations support the use of other off-label biologic therapies. We report on a multicentric retrospective review of patients with HS treated with an ustekinumab dosing schedule of intravenous infusion adjusted by weight, followed by a subcutaneous maintenance dose of 90 mg every 8 weeks, as recently approved for Crohn's disease. The minimal follow-up period required for inclusion was 16 weeks. A total of 14 patients from six hospitals were included. In 50% of the treated patients, therapeutic outcomes, measured by means of the Hidradenitis Suppurativa Clinical Response (HiSCR) and decrease of Dermatology Life Quality Index (DLQI) and visual analog scale (VAS) of pain, were reached at week 16. In 71.42% of patients DLQI and VAS of pain improved, irrespective of achievement of HiSCR. Two patients abandoned treatment due to lack of efficacy or patient preferences. No ustekinumab-related adverse effects were reported. The results are limited by the retrospective nature of the study, the short follow-up period, and the small patient number. This therapeutic regime proved to be safe and showed moderate efficacy in treating HS with failure to previous biologic therapy. Ideally, the efficacy of ustekinumab in HS should be tested in randomized and controlled clinical trials.

Inter- and Intra-rater Agreement of Dermatologic Ultrasound for the Diagnosis of Lobular and Septal Panniculitis.

OBJECTIVES: Dermatologic ultrasound (US) may aid in the diagnosis and classification of panniculitis. The purpose of this study was to assess the capability of dermatologic US for subtyping mainly septal/lobular panniculitis. METHODS: A multicentric and prospective study of the inter- and intra-rater agreement of dermatologic US for subtyping panniculitis was conducted among 4 clinicians with experience in dermatologic US and a radiologist specialized in dermatologic US. Clinicians recruited patients and performed dermatologic US examinations of the most substantial lesion and punch biopsies. A histologic study was considered the reference standard. Then the images were blindly evaluated by all researchers. For intra- and inter-rater agreement, Cohen and Fleiss κ values were calculated. RESULTS: Sixty-four patients were included. The Cohen intra-rater κ was 0.74. Sensitivity and specificity for lobular panniculitis were 85.19 and 88.57, respectively. The Fleiss inter-rater κ was 0.47. Limitations of the study included the small number of patients and differences in evaluators and their dermatologic US equipment. CONCLUSIONS: This study supports the use of US for diagnosing panniculitis. For subtyping panniculitis, the intra-rater correlation was good. Improvement of inter-rater agreement may depend on access to clinical information, dynamic images, a better definition of criteria, homogeneous configurations of the devices, and the expertise of dermatologic US operators.

Photodynamic therapy with intralesional methylene blue and a 635 nm light-emitting diode lamp in hidradenitis suppurativa: a retrospective follow-up study in 7 patients and a review of the literature.

Hidradenitis suppurativa is a chronic inflammatory skin disease which has an estimated prevalence of 1%. It is characterized by the formation of recurrent painful suppurative nodules and abscesses in the flexural areas of the body. It is believed that its pathogenesis involves an aberrant, genetically-determined activation of innate immunity against the bacterial commensal flora of intertriginous areas. It has been found that the formation of antibiotic-resistant bacterial biofilms is a common finding in hidradenitis lesions. Photodynamic therapy with different compounds and light sources has demonstrated its efficacy in a number of infectious diseases such as nail mycosis and chronic periodontitis. We retrospectively report our experience in the treatment of hidradenitis with photodynamic therapy using intralesional methylene blue and a 635 nm light-emitting diode lamp in 7 patients. Two patients received one session whereas 5 patients received two sessions. At one month follow-up good response was achieved in 6 patients. After 6 months, 5 patients (71%) maintained remission of the disease in the treated area. In view of the results and literature review, we regard methylene blue as an ideal photosensitizer for photodynamic therapy in this disease.