The role of biologic treatment in special scenarios in hidradenitis suppurativa: Facial and nape phenotype, dissecting cellulitis of the scalp, and lymphedema.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder affecting the hair follicle which typically affects the axilla, inguinal, submammary, and perianal areas. Atypical HS, such as facial HS, dissecting cellulitis of the scalp (DCS), nape HS, and HS lymphedema has also been described. There is scarce evidence about the treatment of atypical HS. To describe the efficacy of biologic drugs and adjuvant therapeutic interventions used in patients with atypical HS who had an inadequate response to systemic antibiotics. Prospective case series study of patients with atypical HS (facial HS, DCS, nape HS, and HS lymphedema) treated with biologic drugs in a HS Clinic setting. Disease activity indexes, sociodemographic, clinical, and safety variables were collected. Two patients met criteria for Facial HS, three met criteria for DCS/nape HS and three patients met criteria for HS lymphedema. Patients with facial HS achieved rapid improvement without requiring other therapies. Patients with DCS, nape HS, and HS lymphedema showed variable response, with decrease of activity indexes, and requiring adjuvant treatments. Biologic drugs are useful in the management of special HS locations. In the case of facial HS, biologic therapy seems to be quite effective as monotherapy. In the cases of DCS, HS lymphedema and nape HS, treatment combination or intensification may be needed.

Implications of Hidradenitis Suppurativa Phenotypes in Cardiovascular Risk and Treatment Decisions: A Retrospective Cohort Study.

BACKGROUND: New integrative hidradenitis suppurativa (HS) lesion pattern phenotypes have been proposed, an inflammatory phenotype (IP) and a follicular phenotype (FP). They are characterized by different lesion patterns, symptoms, and risks of disease progression. OBJECTIVES: To evaluate whether lesion pattern phenotypes (1) have a different cardiovascular risk factor profile, and (2) are associated with a different therapeutic approach in the setting of an HS clinic. METHODS: A retrospective cohort study was conducted on 233 patients with HS. They were classified according to lesion pattern phenotype criteria. Data regarding cardiovascular risk factors and treatment decisions were gathered. RESULTS: One hundred and seventeen HS patients (50.21%) were classified as FP and 112 (48.07%) as IP. IP was associated with more severe disease and greater impairment of quality of life. Regardless of disease severity, patients with IP may have a higher cardiovascular risk, assessed according to higher C-reactive protein (CRP) levels (12.75 vs. 5.89, p = 0.059). The lesion pattern phenotype also influenced treatment decisions regardless of disease severity. Patients with IP were more likely to be treated with systemic corticosteroids and adalimumab, showing that lesion pattern phenotypes are associated with different therapeutic approaches. CONCLUSIONS: IP is associated with higher CRP values, suggesting a greater cardiovascular risk in these patients and also a different therapeutic approach. This information could help guide dermatologists in the management of HS patients and help to determine future treatment recommendations.

Clinical selection criteria in new clinical trials of hidradenitis suppurativa: External validity and implications on the daily clinical practice.

INTRODUCTION: There are an increasing number of biologic drugs in the pipeline for treating hidradenitis suppurativa (HS). Clinical trials for these drugs usually share the same clinical selection criteria. OBJECTIVES: (a) To describe the clinical profile of HS patients receiving first-line biologic treatment in an HS clinic setting, (b) to assess how this population would meet clinical criteria to participate in a clinical trial, and (c) to assess treatment effectiveness at week 16 in eligible vs non-eligible patients. METHODS: Prospective observational study. Patients were grouped according to their eligibility for clinical trials. The effectiveness of adalimumab was assessed by HiSCR, IHS4-category-change and a-50%-reduction on IHS4 at week 16. RESULTS: Thirty-eight patients were included in the study: eight (21.05%) were eligible for clinical trials and 30 (78.95%) were not. The main reason for non-eligibility was not having an AN count ≥5. Both groups presented similar number of draining tunnels. Effectiveness at week 16 was lower in non-eligible than eligible patients when evaluated by HiSCR-response but similar if evaluated by the IHS4-category-change or the 50%-reduction in IHS4. CONCLUSION: In our population, the external validity of current eligibility criteria for clinical trials is low. Most patients receiving adalimumab in real-life setting would not be eligible for clinical trials.

Paradoxical Hidradenitis Suppurativa in Patients Receiving TNF-α Inhibitors: Case Series, Systematic Review, and Case Meta-Analysis.

BACKGROUND/AIMS: TNF-α inhibitors represent the most advanced approved therapeutic option for moderate and severe forms of hidradenitis suppurativa (HS). However, in recent years, cases of paradoxical HS secondary to the use of these biological drugs have been described, with very few cases reported in the literature. The aims of this study are (1) to present 2 new cases of paradoxical HS and (2) to perform a systematic review of scientific evidence regarding paradoxical HS with TNF-α inhibitors. MATERIAL AND METHODS: This is a retrospective study in which we searched all the cases of paradoxical HS secondary to the use of TNF-α inhibitors published in the literature and included two additional cases observed in our clinical practice. RESULTS: A total of 34 patients under TNF-α inhibitor treatment were included (adalimumab = 21; infliximab = 9; etanercept = 4). The median delay from exposure to TNF-α inhibitor and the development of paradoxical HS was 12 months (range 1-72). The majority of patients were Hurley stage II (58.8%). Clinical improvement and complete remission were more frequent when the TNF-α inhibitor was stopped or switched to another biological agent with a different therapeutic target rather than maintenance or change to another TNF-α inhibitor. CONCLUSIONS: Paradoxical HS is an unusual adverse effect of TNF-α inhibitors. When this adverse effect appears, interruption or substitution of treatment is associated with a better clinical outcome.

Cutaneous Manifestations of Granulomatosis with Polyangiitis: A Case Series Study.

The aim of this study was to determine the prevalence and type of cutaneous manifestations which occur in patients with granulomatosis with polyangiitis and to explore the potential association between cutaneous and systemic involvement in these patients. A retrospective case series study was designed, including all granulomatosis with polyangiitis cases diagnosed between 2010 and 2018 at the Hospital Universitario Virgen de las Nieves. Thirty-nine patients with granulomatosis with polyangiitis were identified, of which 53.85% presented cutaneous manifestations. In decreasing order of frequency, the types of cutaneous problems observed included: palpable purpura, mucocutaneous ulcers, subcutaneous nodules, pyoderma gangrenosum-like ulcers, digital necrosis, papulonecrotic lesions and livedo reticularis. Patients with palpable purpura presented a higher frequency of renal involvement (p = 0.008). Cutaneous manifestations of granulomatosis with polyangiitis may facilitate early disease diagnosis. Likewise, a manifestation such as palpable purpura may be a predictor of kidney damage.

Vascular malformations syndromes: an update.

PURPOSE OF REVIEW: To provide an update of vascular malformation syndromes by reviewing the most recent articles on the topic and following the new International Society for the Study of Vascular Anomalies (ISSVA) 2018 classification. RECENT FINDINGS: This review discusses the main features and diagnostic approaches of the vascular malformation syndromes, the new genetic findings and the new therapeutic strategies developed in recent months. SUMMARY: Some vascular malformations can be associated with other anomalies, such as tissue overgrowth. PIK3CA-related overgrowth spectrum (PROS) is a group of rare genetic disorders with asymmetric overgrowth caused by somatic mosaic mutations in PI3K-AKT-mTOR pathway that encompass a heterogeneous group of rare disorder that are associated with the appearance of overgrowth. CLOVES syndrome and Klippel-Trénaunay syndrome are PROS disease. Proteus syndrome is an overgrowth syndrome caused by a somatic activating mutation in AKT1. CLOVES, Klippel-Trénaunay and Proteus syndromes are associated with high risk of thrombosis and pulmonary embolism. Hereditary hemorrhagic telangiectasia is an autosomic dominant disorder characterized by the presence of arteriovenous malformations. New therapeutic strategies with bevacizumab and thalidomide have been employed with promising results.

Potential Predictors of Cardiovascular Risk Improvement in Patients with Hidradenitis Suppurativa Treated with Adalimumab: A Pivotal Study of Factors Associated with Carotid Intima-Media Thickness Reduction.

INTRODUCTION: Hidradenitis suppurativa (HS) has been linked to higher cardiovascular risk (CVR) due to its inflammatory burden. There is little evidence on how biologic treatment could modify the cardiovascular risk of patients with HS. The aims of the present study were to explore the modification of CVR in patients under adalimumab treatment and to explore the potential factors associated with CVR improvement. METHODS: A prospective longitudinal study was performed. A cohort of patients with HS treated with adalimumab was followed up. Carotid intima-media thickness (IMT) and other clinical and biochemical CVR factors were collected at baseline and 32 weeks after starting the treatment. RESULTS: Twenty-seven patients with severe HS were included. Overall, there were no differences in IMT between baseline (633 µm) and 32 weeks follow-up (634 µm). However, 40.7% (11/27) of the patients presented an improvement in IMT. This group (IMT responders) had a higher prevalence of dyslipidemia, diabetes mellitus, higher HbA1c levels, consumed more tobacco, and had higher BMI at baseline. Moreover, these patients had lower IHS4 scores at baseline and tended to have a greater IMT basal value, indicating a higher burden of subclinical atherosclerosis. CONCLUSIONS: Adalimumab treatment might benefit a subset of patients with HS in terms of cardiovascular risk reduction. In light of the results of the present study patients with classical cardiovascular risk factors, and those with higher burden of subclinical atherosclerosis and with less inflammatory load, may be more likely to improve their IMT during adalimumab treatment.

Exploring the role of systemic immune-inflammation index and neutrophil-lymphocyte ratio in cardiovascular risk stratification for patients with hidradenitis suppurativa: A cross-sectional study.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicle that has previously been associated with a higher cardiovascular risk (CVR). Although different methods have been described for CVR stratification in HS, there is little evidence about the role of hemogram indexes in CVR in HS. Given its potential convenience, the aim of this study was to assess the role of the hemogram indexes systemic immune-inflammation index (SII) and neutrophil-lymphocyte ratio (NLR) in CVR stratification for patients with HS. A cross-sectional study was performed to assess the role of SII and NLR in CVR stratification in patients with moderate to severe HS who were candidates for biologic therapy. SII, NLR, carotid intima-media thickness, and other clinical and biochemical CVR factors were assessed before the start of the treatment. Fifty patients were included. The male:female ratio was 3:2, and the mean International Hidradenitis Suppurativa Severity Score System score was 21.6. After multivariate analysis, SII correlated with higher values of systolic blood pressure, metabolic syndrome, and higher risk of insulin resistance (p < 0.05). NLR was associated with insulin resistance (p < 0.05). These associations were independent of age, sex, body mass index, severity of the disease, and tobacco consumption. The implementation of SII and NLR in daily practice may be of benefit for identifying patients with HS at higher risk of high blood pressure, insulin resistance, or metabolic syndrome. Since these indexes are simple to calculate, they could be used as a screening tool in HS-specific units.

Itchy Capillary Malformations: Unusual Appearance of Meyerson Phenomenon, a Case Series.

Meyerson phenomenon, also known as "halo-eczema," has been widely described over melanocytic and non-melanocytic lesions. However, its appearance over vascular anomalies is rarely observed and could lead to diagnostic errors. A case study of five patients aged between four months and two years is reported. These patients developed unique erythematous and pruritic scaly patches, being diagnosed and treated as fungal infections. Due to the lack of response to the treatment, they were referred to the pediatric dermatology practice, where the diagnosis of Meyerson phenomenon over capillary malformations was made. Topical treatment with corticosteroids led to improvement in all cases. Although Meyerson phenomenon developing over vascular anomalies is a rare condition, it is important for pediatricians and dermatologists to assess it as a part of the differential diagnosis when treating a patient with skin lesions. Recognizing this phenomenon will prevent diagnostic and therapeutic errors.

Systemic Minoxidil Accidental Exposure in a Paediatric Population: A Case Series Study of Cutaneous and Systemic Side Effects.

Oral minoxidil is an approved treatment for high blood pressure which is also used as an off-label drug for alopecia. Knowledge about the effects of systemic minoxidil in the paediatric population is limited. A retrospective case series study of paediatric patients with history of systemic minoxidil intake due to contaminated sets of omeprazole was performed to describe side effects of high dose oral minoxidil intake in children. Twenty patients aged between 2 months and 13 years joined the study. They had received high doses of oral minoxidil (mean dose 0.90 mg/kg/day) during a mean time of 38.3 days. Hypertrichosis appeared in 65%, with a mean latency time of 24.31 days. Treatment time was associated with the appearance of hypertrichosis (p < 0.05). Most common initial zone of hypertrichosis was the face. Systemic effects developed in 15%, with no cases of severe disorders. The present study shows a novel insight into the side effects of high doses of oral minoxidil in children.

Cumulative Inflammation and HbA1c Levels Correlate with Increased Intima-Media Thickness in Patients with Severe Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that has been associated with a greater risk of metabolic and cardiovascular comorbidities. The aim of this study is to assess cardiovascular risk by means of intima-media thickness (IMT), metabolic syndrome, and other potential biomarkers in patients with severe hidradenitis suppurativa who are candidates for biologic therapy and to explore potentially associated factors. A cross-sectional study was performed. Body mass index (BMI), carotid intima-media thickness (IMT), and blood tests, including glycemic and lipid profile, insulin, vitamin D, and inflammation markers were performed. Fifty patients were included in the study; the male/female ratio was 3:2. The mean age was 38 years, and the mean disease duration was 21.8 years. The mean carotid IMT was 651.39 µm. A positive association of IMT with disease duration, tobacco consumption, and HbA1c levels was observed. HbA1c correlated with the age of onset, hypertension, metabolic syndrome, and glucose levels. Vitamin D levels inversely correlated with the number of areas affected. In conclusion, patients with severe HS present a higher cardiovascular risk, but it is not distributed equally within the patients: Tobacco consumption, inadequate glycemic control, and disease duration could be useful clinical and biochemical markers to identify patients at higher risk.

Reproductive Potential and Outcomes in Patients with Hidradenitis Suppurativa: Clinical Profile and Therapeutic Implications.

There are scarce data available regarding the impact of hidradenitis suppurativa (HS) on fertility, course and outcome of pregnancy and risk associated with treatments. The aims of this study are (1) to describe the clinical profile of HS women of childbearing age with and without accomplished reproductive desires and (2) to describe the prescribed treatments based on the fulfillment of reproductive intentions. We conducted a prospective observational study that included 104 HS women of childbearing age, 50.96% (53/104) with unfulfilled reproductive desires. These women were younger (29.08 vs. 42.06 years, p < 0.001), less frequently married and higher educated than women with fulfilled reproductive desires. Their age of disease onset was lower, but disease duration was shorter, in concordance with a lower International Hidradenitis Suppurativa Severity Score System (IHS4) and lower number of draining tunnels. Combined oral contraceptives were more frequently prescribed in women with unfulfilled reproductive desires (30.19% vs. 9.80%, p = 0.013) while biologics were less used in this group (3.77% vs. 13.73%, p = 0.08). In conclusion, a higher educational level and an earlier disease onset, with potential implications in finding a partner, may make the fulfillment of reproductive desires difficult for patients with HS. This study could help clinicians to achieve a better understanding of the specific characteristics of HS during childbearing age and consider reproductive desires when making treatment decisions.