Differentiating clinical characteristics of perianal inflammatory bowel disease from perianal hidradenitis suppurativa.

BACKGROUND: Perianal draining tunnels in hidradenitis suppurativa (HS) and perianal fistulizing inflammatory bowel disease (IBD) present diagnostic and management dilemmas. METHODS: We conducted a retrospective chart review of patients with perianal disease evaluated at Mayo Clinic from January 1, 1998, through July 31, 2021. Patients' demographic and clinical data were extracted, and 28 clinical features were collected. After experimenting with several machine learning techniques, random forests were used to select the 15 most important clinical features to construct the diagnostic prediction model to distinguish perianal HS from fistulizing perianal IBD. RESULTS: A total of 263 patients were included (98 with HS, 100 with IBD, and 65 with both IBD and HS). Patients with HS had a higher mean body mass index, a higher smoking rate, and more commonly showed cutaneous manifestations of tunnels and comedones, while fistulas, abscesses, induration, anal tags, ulcers, and anal fissures were more common in patients with IBD. In addition to having lesions in the perianal area, patients with IBD often had lesions in the buttocks and perineum, while those with HS had additional lesions in the axillae and groin. Among the statistically significant features, the 15 most important were identified by random forest: fistula, tunnel, digestive symptom, knife-cut ulcer, perineum, body mass index, age, axilla, abscess, tags, smoking, groin, genital cutaneous edema, erythema, and bilateral/unilateral. CONCLUSIONS: The results of this study may help differentiate perianal lesions, especially perineal HS and fistulizing perineal IBD, and provide promise for a better therapeutic outcome.

Stevens-Johnson syndrome and toxic epidermal necrolysis-like eruptions in patients treated with immune checkpoint inhibitors: a systematic review.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by targeting immune checkpoints such as PD-1, PDL-1, and CTLA-4, but concerns about severe immune-related adverse events persist. The scarcity of literature on dermatologic implications, especially severe reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), highlights the urgent need for investigation. OBJECTIVE: Our systematic review aims to address the gap in relevant literature by extensively examining the epidemiologic risk factors and management of SJS/TEN-like illnesses in ICI-treated patients to provide insights for risk assessment and clinical care. METHODS: We identified 158 case reports that detailed the incidence of SJS/TEN in patients being treated with ICIs, examining demographic patterns, type of malignancy, clinical characteristics, and treatments linked to onset. We assessed mortality rates, risk elements, and the effectiveness of interventions to help guide clinical care. RESULTS: Analysis of 158 case reports revealed that SJS/TEN in ICI users is typically seen on average at the age of 63 and is more common in males. PD1 inhibitors such as nivolumab and pembrolizumab are often associated with various mucocutaneous patterns and significant risks with ICI use, especially TEN, which is linked to high morbidity and mortality rates. LIMITATIONS: Our study notes limitations due to the inclusion of case reports or case series, such as potential publication and reporting biases, leading to skewed findings. Additionally, because of the heterogeneous reporting standards, the retrospective nature limits phenotypic precision, control for confounding variables, and data completeness. CONCLUSION: Our study provides valuable insights into the epidemiology, clinical features, management strategies, and outcomes of ICI-induced SJS/TEN, underscoring the importance of vigilant monitoring and personalized risk assessment in oncology practice. Continued research efforts are essential to optimize patient outcomes and enhance the safety profile of ICIs in cancer therapy.

Management of pyoderma gangrenosum during pregnancy and breastfeeding: a systematic review.

Pregnancy is a conjectured risk factor for pyoderma gangrenosum (PG), an autoinflammatory neutrophilic dermatosis characterized by painful ulcers. Even so, there are no available treatment guidelines for those with PG who are pregnant or breastfeeding. To describe existing treatment options, we systematically reviewed the literature on PG treatment in pregnant or breastfeeding patients. A search over four databases was completed in October 2022. Independent reviewers accomplished screening and data extraction. 18 articles met the inclusion criteria. 15 cases involved the treatment of PG during pregnancy, and three cases involved the treatment of PG while breastfeeding. Most patients did not have a history of PG prior to pregnancy (77.7%), and most did not have PG-associated comorbidity (61.1%). Of the cases involving treatment of PG during pregnancy, the majority (73%) found treatment success with a systemic corticosteroid (SCS). Only three cases reported an adverse outcome, including premature rupture of membranes and premature birth (16.7%); all these cases involved treatment with a SCS at >0.5 mg/kg/day during pregnancy. We present a treatment algorithm for pregnant or breastfeeding patients with PG. Our findings suggest prioritizing topicals and TNF inhibitors due to more favorable side effect profiles. However, there is a paucity of data on the safety of PG therapies in pregnancy and breastfeeding, and thus, controlled studies and pregnancy registries must be pursued.

Yao syndrome: a novel systemic autoinflammatory disease with cutaneous manifestations.

Yao syndrome (YAOS) is a novel systemic autoinflammatory disease linked to the nucleotide-binding oligomerization domain (NOD2) gene. It is characterized by periodic fevers, gastrointestinal (GI) symptoms, arthritis, and dermatitis, among other symptoms. A sparse literature exists on this disease, and little is known about its dermatological manifestations. A review of available literature was performed to characterize the cutaneous manifestations of Yao syndrome. Cutaneous manifestations were documented in 85.7% of patients, with common characteristic descriptions of erythematous patches and plaques involving the face, trunk, abdomen, and extremities. Based on our review of treatment modalities employed for Yao syndrome, prednisone is an appropriate initial approach, with oral sulfasalazine and other disease-modifying antirheumatic drugs serving as appropriate secondary options. YAOS should be considered in the differential diagnosis of patients presenting with a dermatitic rash, especially in the context of concurrent articular symptoms, periodic fever, and GI symptoms.

Clinical Characteristics and Inciting Agents for Pseudoporphyria: The Mayo Clinic Experience, 1996-2020.

GENERAL PURPOSE: To raise awareness regarding the clinical presentations of patients with pseudoporphyria. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Describe the clinical presentation of pseudoporphyria.2. Identify the differential diagnoses of blistering lesions on hands and feet.3. Outline the management options for patients with porphyria.

Pseudoporphyria is an uncommon immunobullous disease that is clinically and histopathologically similar to porphyria cutanea tarda but without abnormal porphyrin levels. Limited case reports and case series of pseudoporphyria have been published. To describe the clinical characteristics and inciting agents for patients with pseudoporphyria. Health records were retrospectively reviewed for patients treated at an integrated multiregional health system from 1996 through 2020. To report results, the authors used descriptive statistics, median (range) for continuous variables, and number (percentage) for categorical data. In total, 23 patients met the inclusion criteria: 13 men and 10 women. The most common medications causing pseudoporphyria were nonsteroidal anti-inflammatory drugs, the antihypertensive agent hydrochlorothiazide, and retinoids. All patients had blisters and reported photosensitivity. Seven patients (30.4%) also had scarring, and one (4.3%) had milia. All patients had normal porphyrin levels in their serum, urine, and stool. Among patients with remission, symptoms resolved at a median of 2.5 months (range, 1 week to 24 months) after discontinuation of the suspected inciting medication. Four patients, however, had persistent symptoms at a median of 6 months (range, 2­9 months). Because pseudoporphyria is a diagnosis of exclusion, clinicians should familiarize themselves with the presentation and management of this uncommon condition.

Evaluation of Cannabis-Related Product Use Among Patients With Hidradenitis Suppurativa: A Narrative Review.

The use of cannabis and cannabis-related products among patients with hidradenitis suppurativa (HS) is increasing globally. Given the potential anti-inflammatory, therapeutic, and pain management benefits of cannabis-related products, we reviewed primary literature to evaluate the prevalence and possible purpose for cannabis use among patients with HS and to provide recommendations to patients and physicians. A narrative review of original studies was conducted using Embase and Ovid Medline databases. The search strategy was confirmed by a librarian and conducted on September 1, 2023, using a detailed list of subject headings and keywords tailored to cannabis, cannabis-related products, HS, and both adult and pediatric populations. Among 43 identified studies, 6 met the eligibility criteria and encompassed 34,435 patients. Patients were mostly female, and studies were conducted across the United States, Canada, and France. Findings show higher cannabis use among HS patients, demonstrating efficacy in pain management, sleep, anxiety relief, itch relief, and improved quality of life. Cannabis may play a role in analgesia, improved quality of life, pain, itch, and overall mental health in patients with HS and healthcare providers including dermatologists should increase their familiarity in appropriate use of cannabis-related products.

Inpatient Management of Hidradenitis Suppurativa: A Delphi Consensus Study.

Inpatient hospitalization of individuals with hidradenitis suppurativa (HS) has increased. Inpatient services may not be familiar enough with this disease to understand how to manage severe HS and/or HS flares. It would be beneficial to the inpatient medical community to establish consensus recommendations on holistic inpatient care of patients with HS. A survey study was developed and distributed by Wake Forest University School of Medicine (Winston-Salem, North Carolina). A total of 26 dermatologists participated in the Delphi process, and the process was conducted in 2 rounds. Participants voted on proposal statements using a 9-point scale (1=very inappropriate; 9=very appropriate). Statements were developed using current published guidelines for management of HS and supportive care guidelines for other severe inpatient dermatologic diseases. A total of 50 statements were reviewed and voted on between the 2 rounds. Consensus was determined using the RAND/UCLA Appropriateness Method. Twenty-six dermatologists completed the first-round survey, and 24 completed the second-round survey. The 40 consensus recommendations generated through these surveys can serve as a resource for providers caring for inpatients with HS.

IRAK4 Is Overexpressed in Hidradenitis Suppurativa Skin and Correlates with Inflammatory Biomarkers.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting as painful dermal nodules, abscesses, and tunnels. Activation of the IL-1R/toll-like receptor pathway is strongly implicated in the pathogenesis of HS; thus, the role of a key signaling node, IRAK4, was investigated in a noninterventional study (NCT04440410) that enrolled 30 patients with HS. IRAK4 expression was evaluated in blood and lesional, perilesional, and nonlesional skin biopsies. PBMCs expressed IRAK4, with significantly higher levels in monocytes (P ≤ .0001). Ex vivo treatment of PBMCs with KT-474, a targeted degrader of IRAK4, robustly decreased IRAK4 in all immune cell types from healthy volunteers and patients with HS. Ex vivo treatment of toll-like receptor-stimulated healthy donor monocytes with KT-474 decreased IRAK4 protein levels and inhibited inflammatory cytokine production. In HS skin samples, IRAK4 protein levels were significantly higher in lesional than in nonlesional tissue (P ≤ .0001), and IRAK4-positive immune infiltrate increased with greater disease severity. Multiple inflammatory mediators were upregulated in HS lesional skin, correlating with IRAK4 overexpression. These data confirm the significance of the IL-1R/toll-like receptor pathway in the pathogenesis of HS and provide support for ongoing clinical studies evaluating KT-474 in the treatment of HS.

Monoclonal gammopathy in the setting of Pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by ulcerative painful lesions with violaceous undermined borders. Up to 75% of PG cases develop in association with an underlying systemic disease. Monoclonal gammopathy is reportedly a concomitant condition with PG, with studies indicating immunoglobulin (Ig) A gammopathy as the most common. Whether gammopathy is associated with PG or is an incidental finding has been debated. We sought to investigate the association and characteristics of gammopathy in patients with PG. We retrospectively identified PG patients at our institution from 2010 to 2022 who were screened for plasma cell dyscrasia. Of 106 patients identified, 29 (27%) had a gammopathy; subtypes included IgA (41%), IgG (28%), and biclonal (IgA and IgG) (14%). Mean age was similar between those with and without gammopathy (60.7 vs. 55.9 years; P = .26). In addition, hematologic or solid organ cancer developed in significantly more patients with vs. without gammopathy (8/29 [28%] vs. 5/77 [6%]; P = .003). Among the subtypes of gammopathy, IgG monoclonal gammopathy had the highest proportion of patients with subsequent cancer development (4 of 8 patients, 50%). Study limitations include a retrospective, single-institution design with a limited number of patients. Overall, our data show a high prevalence of gammopathy in patients with PG; those patients additionally had an increased incidence of cancer, especially hematologic cancer.

Approach to the Atypical Wound.

The heterogeneity of atypical wounds can present diagnostic and therapeutic challenges; however, as the prevalence of atypical wounds grows worldwide, prompt and accurate management is increasingly an essential skill for dermatologists. Addressing the underlying cause of an atypical wound is critical for successful outcomes. An integrated approach with a focus on pain management and patient engagement is recommended to facilitate enduring wound closure. Advances in treatment, in addition to further research and clinical training, are necessary to address the expanding burden of atypical wounds.

Proof-of-concept study exploring the effect of spesolimab in patients with moderate-to-severe hidradenitis suppurativa: a randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a considerable disease burden. Existing treatment options are limited and often suboptimal; a high unmet need exists for effective targeted therapies. OBJECTIVES: To explore the effects of spesolimab treatment in patients with HS. METHODS: This randomized double-blind placebo-controlled proof-of-clinical-concept (PoCC) study was conducted at 25 centres across 12 countries from 3 May 2021 to 21 April 2022. Patients had moderate-to-severe HS for ≥ 1 year before enrolment. Patients were randomized (2 : 1) to receive a loading dose of 3600-mg intravenous spesolimab (1200 mg at weeks 0, 1 and 2) or matching placebo, followed by maintenance with either 1200-mg subcutaneous spesolimab every 2 weeks from weeks 4 to 10 or matching placebo. The primary endpoint was the percentage change from baseline in total abscess and inflammatory nodule (AN) count at week 12. Secondary endpoints were the absolute change from baseline in the International Hidradenitis Suppurativa Severity Score System (IHS4), percentage change from baseline in draining tunnel (dT) count, the proportion of patients achieving a dT count of 0, absolute change from baseline in the revised Hidradenitis Suppurativa Area and Severity Index (HASI-R), the proportion of patients achieving Hidradenitis Suppurativa Clinical Response (HiSCR50), the proportion of patients with ≥ 1 flare (all at week 12) and patient-reported outcomes. RESULTS: In this completed trial, randomized patients (n = 52) received spesolimab (n = 35) or placebo (n = 17). The difference vs. placebo in least squares mean is reported. At week 12, the percentage change in total AN count was similar between treatment arms: -4.1% [95% confidence interval (CI) -31.7 to 23.4]. There was greater numerical improvement in the spesolimab arm, as measured by IHS4 (13.9, 95% CI -25.6 to -2.3); percentage change from baseline in dT count (-96.6%, 95% CI -154.5 to -38.8); and the proportion of patients achieving a dT count of 0 (18.3%, 95% CI -7.9 to 37.5). Spesolimab treatment also improved HASI-R and HiSCR50 vs. placebo. Spesolimab demonstrated a favourable safety profile, similar to that observed in trials in other diseases. CONCLUSIONS: This exploratory PoCC study supports the development of spesolimab as a new therapeutic option in HS.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects approximately 0.4% to 1% of people worldwide. HS mainly affects areas where skin touches skin and can result in painful lumps and abscesses. Tunnel-shaped structures often form below the skin and discharge pus and can greatly affect a person's quality of life. In this study, we tested a drug called 'spesolimab' as a treatment for people with moderate-to-severe HS. Spesolimab is a medicine in development that affects the immune system. This 12-week study included 52 adults who had moderate-to-severe HS for at least 1 year, from North America, Europe and Australia. People who took part were selected at random to receive either spesolimab or placebo. Thirty-five people received spesolimab and 17 received placebo into a vein once a week for 3 weeks, starting at week 0. They then received four injections of spesolimab or placebo under the skin once every 2 weeks until week 10. The number of lumps and abscesses, tunnels and a score based on their combination, called the International Hidradenitis Suppurativa Severity Score System (IHS4), were evaluated before spesolimab or placebo were given, and at week 12. We found that spesolimab and the placebo had a similar effect on the number of lumps and abscesses. However, more people treated with spesolimab showed improvements in tunnels and IHS4 score than those who received the placebo. The safety of spesolimab was favourable, similar to when spesolimab has been used in studies of other diseases. Our findings support further research into the use of spesolimab as a medicine for HS.

Lower Extremity Angiosarcoma: A Life-Threatening Complication of Lymphedema.

ABSTRACT: When angiosarcoma, a rare and aggressive tumor of the soft tissue, develops in the setting of chronic lymphedema, it is referred to as Stewart-Treves syndrome. It is usually seen in chronic lymphedema of the upper limbs postmastectomy. Angiosarcoma developing in the lower limb in the setting of chronic lymphedema is rare and has a poor outcome. The presentation of angiosarcoma can vary, ranging from a bleeding papule to a plaque or a subcutaneous mass, which can later progress to ulceration or necrosis. Treatment for Stewart-Treves syndrome is aggressive because of its poor prognosis and usually requires a multidisciplinary approach of surgery, radiation, and chemotherapy. Several theories have been put forth to explain the mechanism of Stewart-Treves syndrome, but it remains ambiguous. The current literature regarding angiosarcoma developing in the setting of chronic lymphedema in the lower limb is limited to single case reports. Herein, the authors report a series of six cases of biopsy-proven angiosarcoma in the setting of lower extremity lymphedema. Providers should include angiosarcoma in the differential diagnosis of ulcerative or vascular tumors arising in the context of lower extremity lymphedema.

Discrepancies in hidradenitis suppurativa lesion characterization by providers and patients.

BACKGROUND: The hidradenitis suppurativa (HS) clinical response (HiSCR) has come under scrutiny as several HS clinical trials failed to meet primary endpoints with high placebo responses. This may be due to limitations of the tool and raters' ability to accurately characterize and count lesions, rather than lack of efficacy of the studied drug. Due to HS lesion complexity and potential differences in rater training, it was hypothesized that there would be discrepancies in how providers characterize and count lesions for HS clinical trials. OBJECTIVE: To evaluate how HS providers and patients name and count HS lesions and to identify discrepancies among providers to initiate the development of consensus-driven guidance for HS rater training. METHODS: An online survey was distributed to the members of HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC). Respondents were asked to classify lesion images composed of multiple and different morphology types and answer questions regarding inclusion of associated dermatological conditions. RESULTS: Forty-seven HISTORIC members responded (29 providers; 18 patients). There was variability in how respondents classified HS lesions. Of 12 questions containing images, four had ≥50% of respondents choosing the same answer. With an image of a lesion composed of different morphologies, 45% of providers counted it as a single lesion and 45% counted it as multiple distinct lesions. With an image of multiple interconnected draining tunnels, 7% of providers classified it as a single draining tunnel while 79% categorized it as multiple draining tunnels with the number estimated by visual inspection. There was also variability in deciding whether lesions occurring in associated conditions should be considered separately or included in HS lesion counts. Patient responses were also variable. CONCLUSIONS: The result of the current study reaffirms the gap in how providers characterize and count HS lesions for clinical trials and the need to develop consensus-driven rater training related to HS outcome measures.

Inflammatory and vaso-occlusive ulcers: Part I - clinical presentation and diagnosis.

In this CME, we review two specific categories of ulcers: inflammatory (where inflammation is the primary pathologic process leading to ulceration) and vaso-occlusive (where occlusion is the primary process). Inflammatory ulcers include pyoderma gangrenosum and vasculitides, whereas livedoid vasculopathy, calciphylaxis and Martorell ulcers are vaso-occlusive ulcers. Determining the causes of ulcers in these conditions may require laboratory evaluation, biopsy and imaging.

Inflammatory and vaso-occlusive ulcers: Part II - Management.

In the second part of this CME, we present an approach for the management of inflammatory and vaso-occlusive ulcers and highlight the need for further research in this field. The three overarching principles for management are etiology-specific treatment, ulcer care, and consideration of patient comorbidities and risk factors for poor healing. Both etiology-specific treatment and management of patient comorbidities and risk factors often require collaboration with providers from other specialties. Ulcer care is governed by TIME, or tissue debridement, infection control, management of moisture imbalance and epithelial edge advancement. As wound healing is a dynamic process, management should be adapted to changes in the status of the ulcer.