Management of Adult Patients With Drug Reaction With Eosinophilia and Systemic Symptoms: A Delphi-Based International Consensus.

Importance: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. To our knowledge, there is no international consensus on its severity assessment and treatment. Objective: To reach an international, Delphi-based multinational expert consensus on the diagnostic workup, severity assessment, and treatment of patients with DRESS. Design, Setting, and Participants: The Delphi method was used to assess 100 statements related to baseline workup, evaluation of severity, acute phase, and postacute management of DRESS. Fifty-seven international experts in DRESS were invited, and 54 participated in the survey, which took place from July to September 2022. Main Outcomes/Measures: The degree of agreement was calculated with the RAND-UCLA Appropriateness Method. Consensus was defined as a statement with a median appropriateness value of 7 or higher (appropriate) and a disagreement index of lower than 1. Results: In the first Delphi round, consensus was reached on 82 statements. Thirteen statements were revised and assessed in a second round. A consensus was reached for 93 statements overall. The experts agreed on a set of basic diagnostic workup procedures as well as severity- and organ-specific further investigations. They reached a consensus on severity assessment (mild, moderate, and severe) based on the extent of liver, kidney, and blood involvement and the damage of other organs. The panel agreed on the main lines of DRESS management according to these severity grades. General recommendations were generated on the postacute phase follow-up of patients with DRESS and the allergological workup. Conclusions and Relevance: This Delphi exercise represents, to our knowledge, the first international expert consensus on diagnostic workup, severity assessment, and management of DRESS. This should support clinicians in the diagnosis and management of DRESS and constitute the basis for development of future guidelines.

Outcome Measures for the Evaluation of Treatment Response in Hidradenitis Suppurativa for Clinical Practice: A HiSTORIC Consensus Statement.

Importance: Although several clinician- and patient-reported outcome measures have been developed for trials in hidradenitis suppurativa (HS), there is currently no consensus on which measures are best suited for use in clinical practice. Identifying validated and feasible measures applicable to the practice setting has the potential to optimize treatment strategies and generate generalizable evidence that may inform treatment guidelines. Objective: To establish consensus on a core set of clinician- and patient-reported outcome measures recommended for use in clinical practice and to establish the appropriate interval within which these measures should be applied. Evidence Review: Clinician- and patient-reported HS measures and studies describing their psychometric properties were identified through literature reviews. Identified measures comprised an item reduction survey and subsequent electronic Delphi (e-Delphi) consensus rounds. In each consensus round, a summary of outcome measure components and scoring methods was provided to participants. Experts were provided with feasibility characteristics of clinician measures to aid selection. Consensus was achieved if at least 67% of respondents agreed with use of a measure in clinical practice. Findings: Among HS experts, response rates for item reduction, e-Delphi round 1, and e-Delphi round 2 surveys were 76.4% (42 of 55), 90.5% (38 of 42), and 92.9% (39 of 42), respectively; among patient research partners (PRPs), response rates were 70.8% (17 of 24), 100% (17 of 17), and 82.4% (14 of 17), respectively. The majority of experts across rounds were practicing dermatologists with 18 to 19 years of clinical experience. In the final e-Delphi round, most PRPs were female (12 [85.7%] vs 2 males [11.8%]) and aged 30 to 49 years. In the final e-Delphi round, HS experts and PRPs agreed with the use of the HS Investigator Global Assessment (28 [71.8%]) and HS Quality of Life score (13 [92.9%]), respectively. The most expert-preferred assessment interval in which to apply these measures was 3 months (27 [69.2%]). Conclusions and Relevance: An international group of HS experts and PRPs achieved consensus on a core set of HS measures suitable for use in clinical practice. Consistent use of these measures may lead to more accurate assessments of HS disease activity and life outcomes, facilitating shared treatment decision-making in the practice setting.

Successful treatment of necrobiosis lipoidica and associated retinal vasculitis with tumor necrosis factor (TNF)-alpha inhibitor.

Purpose: To report the clinical and histopathologic features of necrobiosis lipoidica and associated retinal vasculitis and describe successful treatment of both skin and eye manifestations with adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor. Observations: A 35-year-old patient with bipolar disorder and ocular hypertension was referred for evaluation of bilateral retinal vasculitis. Fluorescein angiography revealed bilateral occlusive retinal vasculitis. Physical exam was notable for multiple annular and round erythematous hyperpigmented and atrophic patches and plaques on both lower extremities. Skin biopsy revealed a diagnosis of necrobiosis lipoidica, a rare granulomatous skin disease. Both the patient's retinal vasculitis and skin patches responded favorably to treatment with adalimumab, a TNF-alpha inhibitor. Conclusions and importance: This case highlights the importance of obtaining a complete history and physical exam in patients who present with ocular inflammation, as extraocular manifestations of disease may be present. It also demonstrates the effectiveness of a multidisciplinary approach to evaluation and management of these patients, as both skin and eye involvement were successfully treated with adalimumab, a TNF-alpha inhibitor.

A patient with anti-NXP2-positive dermatomyositis and syphilis.

Dermatomyositis is an auto-immune inflammatory myopathy that primarily affects the skin and muscle and can be triggered by exposure to various environmental factors. We present a patient with active syphilis infection who developed dermatomyositis and discuss the significance of anti-NXP2 autoantibody positivity.

North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part II: Topical, intralesional, and systemic medical management.

Hidradenitis suppurativa is a severe and debilitating dermatologic disease. Clinical management is challenging and consists of both medical and surgical approaches, which must often be combined for best outcomes. Therapeutic approaches have evolved rapidly in the last decade and include the use of topical therapies, systemic antibiotics, hormonal therapies, and a wide range of immunomodulating medications. An evidence-based guideline is presented to support health care practitioners as they select optimal medical management strategies and is reviewed in this second part of the management guidelines. A therapeutic algorithm informed by the evidence available at the time of the review is provided.

North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part I: Diagnosis, evaluation, and the use of complementary and procedural management.

Hidradenitis suppurativa is a chronic inflammatory disorder affecting hair follicles, with profoundly negative impact on patient quality of life. Evidence informing ideal evaluation and management of patients with hidradenitis suppurativa is still sparse in many areas, but it has grown substantially in the last decade. Part I of this evidence-based guideline is presented to support health care practitioners as they select optimal management strategies, including diagnostic testing, comorbidity screening, and both complementary and procedural treatment options. Recommendations and evidence grading based on the evidence available at the time of the review are provided.

Proceeding report of the Symposium on Hidradenitis Suppurativa Advances (SHSA).

Hidradenitis Suppurativa (HS) is a chronic debilitating skin condition that impairs the productivity and the quality of patients` lives. HS has recently drawn lots of attention among scholars to further expand their knowledge but it still loads with uncertainties and gaps to be explored. This publication addresses these uncertainties, and provides a road-map for researchers, scholars and clinicians from different disciplines for their future studies about HS. This is a proceeding report of the first Symposium on Hidradenitis Suppurativa Advances (SHSA), and it reviews the scientific sessions about the epidemiology, pathophysiology, presentations, and management of HS. This symposium was a great opportunity for experts in the HS field to exchange their knowledge, and improve their mutual understanding of this disease.

Pyoderma Gangrenosum: An Update on Pathophysiology, Diagnosis and Treatment.

Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic disorder with prototypical clinical presentations. Its pathophysiology is complex and not fully explained. Recent information regarding the genetic basis of PG and the role of auto-inflammation provides a better understanding of the disease and new therapeutic targets. PG equally affects patients of both sexes and of any age. Uncontrolled cutaneous neutrophilic inflammation is the cornerstone in a genetically predisposed individual. Multimodality management is often required to reduce inflammation, optimize wound healing, and treat underlying disease. A gold standard for the management of PG does not exist and high-level evidence is limited. Multiple factors must be taken into account when deciding on the optimum treatment for individual patients: location, number and size of lesion/ulceration(s), extracutaneous involvement, presence of associated disease, cost, and side effects of treatment, as well as patient comorbidities and preferences. Refractory and rapidly progressive cases require early initiation of systemic therapy. Newer targeted therapies represent a promising pathway for the management of PG, and the main focus of this review is the management and evidence supporting the role of new targeted therapies in PG.

Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies.

BACKGROUND: Pyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood. OBJECTIVE: Use data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology. METHODS: Ten PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysis via quantitative real-time PCR. RESULTS: All PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvolved skin triggered ulceration only in the latter. On immunohistochemistry, healed PG scars showed complete loss of pilosebaceous units, which were present in normal skin, and to a lesser extent in control scars, and discoid scars. Early PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather than neutrophils. These early inflammatory events were dominated by increased gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and transcription factors consistent with Th1 phenotype. LIMITATIONS: Small sample size was the main limitation. CONCLUSION: We put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units.

Disfiguring ulcerative neutrophilic dermatosis secondary to doxycycline and isotretinoin in an adolescent boy with acne conglobata.

Acne fulminans is an uncommon and debilitating disease that presents as an acute eruption of nodular and ulcerative acne lesions in association with systemic symptoms. It occurs commonly during treatment of severe acne (eg, acne conglobata) with isotretinoin in young adolescent male patients. Isotretinoin and doxycycline also can potentially induce development of neutrophilic dermatoses in patients with severe acne lesions, which are characterized by the acute appearance of painful ulcerative papulonodules accompanied by systemic symptoms including fever and leukocytosis. We report a challenging case of a 13-year-old adolescent boy who acutely developed hundreds of ulcerative plaques as well as systemic symptoms after being treated with doxycycline and isotretinoin for acne conglobata. He was treated with prednisone, dapsone, and colchicine and had to switch to cyclosporine to achieve relief from his condition.

Hidradenitis Suppurativa and the Association With Hematological Malignancies.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease affecting skin sites with a high density of apocrine glands. HS commonly presents after puberty, with most patients diagnosed in the second decade of their life. Several studies have investigated smoking, obesity, hypertension, diabetes, and dyslipidemia as possible underlying risk factors for HS. However, we encountered 2 patients with a long-standing history of untreated leukemia who developed late-onset HS. OBJECTIVE: To investigate the presence of malignancy as an underlying risk factor for development of HS. METHOD: The PubMed and Scopus databases were searched for keywords such as hidradenitis suppurativa, malignancy, cancer, and epidemiology. OBSERVATION: Only 1 retrospective Swedish study with 2119 patients investigated the prevalence of cancer, including 6 hematopoietic malignancies, in HS patients. However, the study did not assess the timeline of developing HS in relation to the cancer diagnosis. We report 2 patients with a long-standing history of hematopoietic cancers who received no continuous treatments for their malignancies and developed late-onset HS: a 60-year-old male patient with hairy cell leukemia and a 68-year-old male patient with chronic lymphocytic leukemia who developed HS later in life. CONCLUSION: Multiple epidemiologic studies found the average age of HS diagnosis to be well prior to the fourth decade of life. The latency of the HS diagnosis as well as the presence of long-standing leukemia in both of our patients raises the necessity for assessing the possibility of malignancy, especially hematopoietic cancer, as a risk factor for HS. LIMITATION: This is a small retrospective analysis including only 2 patients. Larger studies would better assess the role of malignancy, leukemia in particular, as a possible risk factor for development of HS.

Relapsing Polychondritis: A Review and Guide for the Dermatologist.

Relapsing polychondritis, or RP, is a rare connective tissue disease characterized by relapsing-remitting destructive inflammation of the cartilaginous and other proteoglycan-rich structures in the body. Given the relatively low incidence of RP, a concise clinically relevant guide, focusing on the cutaneous manifestations of this serious disease, is lacking. In this review, we provide the dermatologist with an approach to diagnosing RP and a guide to its initial work-up, and management. We close with an overview of the currently available treatment modalities for RP.