Analysis of Characteristics and Trends in Treatment Response of Hidradenitis Suppurativa Patients: A Southern US Cohort Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that has a substantial impact on patients' quality of life. As the exact pathogenesis remains unclear, treatment is complex and not yet standardized. OBJECTIVES: The aim of this study was to describe patient characteristics and to broadly examine trends in treatment response of various therapeutic strategies in patients with HS in a single academic referral center in the southern USA. METHODS: A retrospective chart review was conducted of a cohort of HS patients seen in a faculty general dermatology practice with academic affiliation to Baylor University Medical Center in Dallas, TX, between February 2015 and February 2018. Patient demographics, clinical features, prescribed treatments, and response to treatment were analyzed using the Pearson χ2 test or Fisher exact test, and by the Mann-Whitney U test for categorical and continuous variables, respectively. RESULTS: A total of 149 patients (113 females, 36 males) were included. Hurley stages I, II, and III were diagnosed in 29.6, 36.5, and 33.9% of patients, respectively. 44.2% of patients had a positive family history of HS, 39.5% of patients were current or former smokers, and 52.8% reported alcohol use. 80.9% of patients were overweight or obese (BMI ≥25), compared to 68.5% in Texas in 2016 (p = 0.0012). The most frequently prescribed treatments were oral antibiotic therapy (83.9%), topical antibiotic therapy (74.5%), metabolic medications such as metformin/zinc (67.1%), intralesional Kenalog (63.1%), and biologic therapies (tumor necrosis factor-α inhibitors; TNF-α inhibitors; 49%). In examining the response rate, patients with disease localized to the buttocks had significantly higher response rates (60.4 vs. 25%, p = 0.043) and approached statistical significance in responders versus nonresponders in treatment with biologics (p = 0.0632) when compared against all other treatments. CONCLUSIONS: HS is a complex inflammatory skin condition associated with obesity and smoking. In this cohort, the most frequently prescribed therapies were oral and topical antibiotics. However, the use of biologic agents (TNF-α inhibitors) appears to be associated with the most significant treatment response. KEY POINTS: This is the first study to evaluate trends in treatment response of various therapeutic strategies in HS patients at an academic referral center in Dallas, TX, a unique geographic region of the southern USA. Biologic therapy (TNF-α inhibitor) appears to be associated with the most significant treatment response.

IL-17 inhibitors for psoriasis.

The role of the Th17/interleukin (IL)-23 pathway has been well elucidated in psoriasis. The IL-17 family includes 6 cytokines: IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F. Two monoclonal antibodies targeting IL-17A (secukinumab, ixekizumab) and one antibody against the IL-17 receptor (brodalumab) have been approved for the treatment of moderate-to-severe plaque psoriasis. Clinical efficacy, safety, and tolerability of each agent is reviewed.

Spectrum of orocutaneous disease associations: Immune-mediated conditions.

There are a number of diseases that manifest both on the skin and the oral mucosa, and therefore the importance for dermatologists in clinical practice to be aware of these associations is paramount. In the following continuing medical education series, we outline orocutaneous disease associations with both immunologic and inflammatory etiologies.

Spectrum of orocutaneous disease associations: Genodermatoses and inflammatory conditions.

The oral cavity and cutaneous organ systems share a close embryologic origin. Therefore, there are numerous dermatologic conditions presenting with concomitant oral findings of which the dermatologist must be aware. The second article in this continuing medical education series reviews inflammatory orocutaneous conditions and a number of genodermatoses. It is essential for dermatologists to be familiar with oral cavity manifestations associated with dermatologic diseases for prompt diagnosis, management, and appropriate referral to stomatology and dentistry.

BAPoma presenting as an incidental scalp papule: case report, literature review, and screening recommendations for BAP1 tumor predisposition syndrome.

OBJECTIVE: BRCA1-associated protein 1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is associated with an increased risk for aggressive cancers. BAP1-inactivated melanocytic tumors (BIMTs) are observed in 75% of BAP1-TPDS, often presenting as early as the second decade of life. These lesions may serve as a predictive marker to identify patients who carry germline BAP1 mutations and thus are at higher risk of developing associated cancers. Early diagnosis for these malignancies is crucial for curative treatment. METHODS: We report a patient who presented with an incidental scalp papule for which biopsy was consistent with a BIMT. A review of literature was conducted by accessing the PubMed database to delineate present knowledge of BIMTs, assess recommendations for screening of germline BAP1 mutations, and evaluate cancer surveillance strategies for BAP1-TPDS associated cancers. RESULTS: Consensus in literature indicates that genetic evaluation should be encouraged in patients presenting with multiple BIMTs or a new BIMT with significant family history of BAP1-TPDS related cancers. If positive for a germline BAP1 mutation, cancer surveillance should be recommended for early diagnosis and timely intervention. CONCLUSIONS: Further workup should be encouraged in patients who meet the proposed screening criteria for germline BAP1 mutations. Patients could benefit from cancer surveillance for earlier diagnosis, management, and improved outcomes.

Erythema Ab Igne and Malignant Transformation to Squamous Cell Carcinoma.

Erythema ab igne (EAI) is a cutaneous reaction resulting from prolonged exposure to an infrared heat source at temperatures insufficient to cause a burn. It is most commonly reported on the lower extremities and back, and it presents with persistent areas of reticular erythema associated with hyperpigmentation, epidermal atrophy, and telangiectases. Erythema ab igne traditionally is associated with chronic exposure to open fires and coal stoves. More recently, other implicated causes include heating pads, laptop computers, heated furniture, and electric space heaters. Histologic features of squamous atypia with basal layer crowding and loss of maturation throughout the epidermis can be seen in later stages of EAI. Therefore, although EAI is predominantly a chronic pigmentary disorder, a percentage of patients might be at increased risk for cutaneous malignant transformation, including squamous cell carcinoma (SCC).

A Real-World Evaluation of the Long-Term Safety and Efficacy of Infliximab in the Treatment Moderate-to-Severe Psoriasis.

INTRODUCTION: Psoriasis is a chronic immune-mediated inflammatory skin disease that occurs in 2.5-3.5% of the general population. Infliximab (INF), a TNF-α inhibitor biologic agent, is a long-standing efficacious treatment for psoriasis; however, not all patients sustain a long-term response (LTR) because of a number of factors including antibody production. There is a paucity of studies assessing infliximab efficacy over a period ≥ 5 years. METHODS: A retrospective cohort chart review of our clinic patients who had undergone ≥ 5 years of treatment with infliximab for chronic plaque psoriasis was performed. The following variables were recorded and analyzed with the Fisher exact test: age, sex, body mass index ([BMI]; normal weight [NW], overweight [OW], obese [OB]), changes in infliximab strength (dose or frequency), concomitant systemic therapy, and side effects. Clinical improvement was assessed by comparing the total body surface area (tBSA) affected by psoriasis before and after treatment. RESULTS: There was a significant difference in likelihood of achieving LTR between the NW, OW and OB groups (p = 0.044). Non-normal-weight patients (OW + OB) were significantly more likely to achieve and sustain LTR than NW patients (OR 9.07, p = 0.020). There were no other significant associations for the other evaluated variables. LIMITATIONS: Patients who began treatment with infliximab before 2009 (prior to the use of the clinic's electronic medical record) were excluded. The Psoriasis Area and Severity Index (PASI) was not available for this study. CONCLUSION: Surprisingly, patients who are overweight or obese are more likely to obtain long-term clinical benefit in their psoriasis symptoms with infliximab therapy than patients who are normal weight.

Diffuse dermal angiomatosis of the breast.

Diffuse dermal angiomatosis of the breast can be a painful, irritating, and persistent inflammatory condition. It tends to present in middle age and is associated with a number of risk factors, mainly relating to tissue hypoxia. There are no standard treatment guidelines, and current treatment focuses on mitigating tissue hypoxia by addressing atherosclerosis through lifestyle changes and medical and/or surgical intervention. Herein, we present a case of diffuse dermal angiomatosis of the breast, describing the condition and current treatment approaches and the likelihood that this diagnosis is more common than previously believed.

Secukinumab: a review of the anti-IL-17A biologic for the treatment of psoriasis.

Psoriasis is a systemic inflammatory disease associated with numerous comorbidities and a profound impact on patients' quality of life. While its complex immune pathogenesis is still not fully delineated, current evidence supports a fundamental role of the T-helper-17 (TH-17) pathway and its related interleukin-17 (IL-17) cytokine. Thus, new antipsoriatic therapies have been developed to block this key cytokine and its downstream effects. Secukinumab is a fully humanized, monoclonal anti-IL-17A antibody, and the first in its class to be approved by the US Food and Drug Administration for the treatment of moderate to severe plaque psoriasis. It has also been approved for the treatment of active psoriatic arthritis and ankylosing spondylitis. Its clinical efficacy in plaque psoriasis has been well demonstrated in numerous phase II and III clinical trials. In addition, it has shown superiority in clinical trials to current biologic agents including etanercept and ustekinumab, with a safe adverse event profile. In correlation with excellent skin improvements, secukinumab is also associated with significant improvements in health-related quality of life measures. Thus, secukinumab offers the potential for equal, or improved, therapeutic effects compared with other biologics, and is a valuable addition to our current antipsoriatic armamentarium.

Symptomatic hypercalcemia and scarring alopecia as presenting features of sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease most frequently affecting the lungs, lymph nodes, and eyes. Skin involvement occurs in approximately 25% to 35% of cases, with the scalp uncommonly affected. Abnormal calcium metabolism is associated with sarcoidosis and other granulomatous disorders and most commonly presents as hypercalciuria (40%-60%) and, less frequently, hypercalcemia (10%-20%). Symptomatic hypercalcemia is unusual, presenting in <5% of sarcoidosis patients, and rarely results in kidney damage. We report here a case of sarcoidosis presenting with severe symptomatic hypercalcemia (>14 mg/dL, 3.5 mmol/L), scarring alopecia, and acute-on-chronic kidney failure.

Pharmacotherapeutic approaches for treating psoriasis in difficult-to-treat areas.

INTRODUCTION: Despite great therapeutic advancements in psoriasis, four notable difficult-to-treat areas including the scalp, nails, intertriginous (including genitals), and palmoplantar regions, pose a challenge to both physicians and patients. Localized disease of these specific body regions inflicts a significant burden on patients' quality of life and requires an adequate selection of treatments. AREAS COVERED: This manuscript discusses appropriate therapies and important treatment considerations for these difficult-to-treat areas based on the available clinical data from the literature. EXPERT OPINION: Clinical trials assessing therapies for the difficult-to-treat areas have been inadequate. With the first biological clinical trial for genital psoriasis pending publication, it is with hope that other biological agents will be evaluated for region-specific psoriasis. A greater understanding of the genetic and immunologic aspects of regional psoriasis, as well as identification of unique biomarkers, will further guide management decisions. For example, the recent discovery of the IL-36 receptor gene for generalized pustular psoriasis may prove valuable for other forms of psoriasis. Ultimately, identification of the most beneficial treatments for each psoriasis subtype and difficult-to-treat area will provide patients with maximal quality of life.

Anti-IL-23 and Anti-IL-17 Biologic Agents for the Treatment of Immune-Mediated Inflammatory Conditions.

Advancements in the immunopathogenesis of psoriasis have identified interleukin (IL)-23 and IL-17 as fundamental contributors in the immune pathways of the disease. Leveraging these promising therapeutic targets has led to the emergence of a number of anti-IL-23 and -17 biologic agents with the potential to treat multiple conditions with common underlying pathology. The unprecedented clinical efficacy of these agents in the treatment of psoriasis has paved way for their evaluation in diseases such as psoriatic arthritis, Crohn's disease, rheumatoid arthritis, in addition to other immune-mediated conditions. Here we review the IL-23/IL-17 immune pathways and discuss the key clinical and safety data of the anti-IL-23 and anti-IL-17 biologic agents in psoriasis and other immune-mediated diseases.

The impact of biologic agents on health-related quality of life outcomes in patients with psoriasis.

INTRODUCTION: Psoriasis is a common, immune-mediated skin disease often associated with significant physical and psychosocial impairment. Antipsoriatic biologic agents offer patients unparalleled treatment potential in regard to greater skin clearance and overall improved quality of life. Evaluation of the therapeutic efficacy of biologic agents on the full psoriasis disease burden must account for their impact on both physical symptoms, as well as patient-reported, health-related quality of life (HRQoL) measurements. Areas covered: Results from numerous clinical trials demonstrate the significant clinical efficacy of biological agents targeting tumor necrosis factor-α (TNF-α) and the interleukin (IL)-12/23 and IL-17 immune pathways. However, relatively limited data is available evaluating their full effect on quality of life outcomes. This review will discuss the most relevant and up-to-date clinical data on HRQoL measurements related to treatment with these aforementioned biologic agents. Expert commentary: Patient-reported outcomes (i.e. Dermatology Life Quality Index) are being used with increasing frequency in clinical trials, and provide valuable information on the impact of psoriasis on numerous aspects of day-to-day living. These outcomes must also be incorporated in clinical practice, in addition to physical assessment of disease severity, treatment decisions, and therapeutic response in the psoriasis patient population.

Calcipotriene betamethasone dipropionate aerosol foam in the treatment of plaque psoriasis: a review of the literature.

Psoriasis is a common chronic immune-mediated skin disease which has a significant impact on patients' quality of life, and is associated with numerous comorbidities (i.e., psoriatic arthritis, Crohn's disease and cardiovascular disease). A greater understanding of its immunopathogenesis has guided the development of novel, more targeted therapies. Nonetheless, traditional treatment with topical agents, phototherapy and systemic medications is used in the management of the majority of psoriasis patients. Mainstay topical treatments include corticosteroids and vitamin D derivatives. Calcipotriene/betamethasone dipropionate aerosol foam is a novel single product combination, which seeks to provide superior therapeutic efficacy in addition to enhanced cosmetic properties. This article reviews the literature on the pharmacology and clinical data in terms of safety, efficacy and patient satisfaction of this topical medication.

Autoimmune hemolytic anemia associated with trimethoprim-sulfamethoxazole use.

PURPOSE: A case report of drug-induced immune hemolytic anemia (DIIHA) triggered by exposure to trimethoprim-sulfamethoxazole is presented along with a brief review of the pathophysiology of DIIHA and diagnostic considerations. SUMMARY: A 58-year-old woman recently initiated on trimethoprim-sulfamethoxazole for treatment of a urinary tract infection presented to the emergency department with generalized weakness and fatigue. Initial laboratory studies were significant for the following values: hemoglobin concentration, 5.6 g/dL (reference range, 12-15 g/dL); mean corpuscular volume, 116.9 µm3 (reference range, 80-100 µm3); and reticulocyte count, 16% (reference range, 0.5-1.5%). An elevated serum lactate dehydrogenase concentration (646 U/L [reference range, 50-150 U/L]) and a low haptoglobin concentration (<10 mg/dL [reference range, 30-200 mg/dL]) indicated a hemolytic process. A peripheral blood smear revealed spherocytosis. Serologic testing showed antibodies to both immunoglobulin G (IgG) and complement component C3b. An antibody identification panel was nonspecifically positive for a warm-reacting autoantibody (IgG). The combination of clinically evident hemolytic anemia, recent exposure to a newly initiated drug, and serologic evidence strongly suggested DIIHA. Trimethoprim-sulfamethoxazole was promptly discontinued, a total of 6 units of packed red blood cells were transfused, and the patient was treated with methylprednisolone sodium succinate. Clinical and hematologic improvements were observed within a few days. Results of follow-up antibody screening and direct antiglobulin testing 4 weeks after discharge were negative. CONCLUSION: A 58-year-old woman developed warm autoimmune hemolytic anemia after receiving trimethoprim-sulfamethoxazole for 5 days.

Psoriasis and cardiovascular disorders.

Psoriasis is associated with an increased risk of cardiovascular disease and related comorbidities such as diabetes mellitus, metabolic syndrome, dyslipidemia, and obesity. The precise mechanistic links underlying the association between psoriasis and cardiovascular disease remain unknown, however, multiple pathologic mechanisms have been proposed. Shared inflammatory pathways between psoriasis and atherosclerosis are likely involved. Other possible mechanisms include endothelial dysfunction, cytokine dysregulation, platelet upregulation, and dyslipidemia. Additional studies are needed to more clearly define the association between psoriasis and cardiovascular disease. Current, but limited, data suggests that psoriasis treatments targeting inflammation may be able to reduce the cardiovascular risks in this patient population. As new therapies become available, long-term prospective studies will be required to determine their potential effects on cardiovascular risk. This review summarizes the current literature on proposed pathogenic links between psoriasis and cardiovascular disease, the epidemiology of psoriasis and associated cardiovascular and cardiometabolic diseases, and the impact of anti-psoriatic treatments on cardiovascular risk profile. In addition, we provide a brief discussion of risk factor management strategies in patients with psoriasis.

Melanoma Development and Progression Are Associated with Rad6 Upregulation and ß -Catenin Relocation to the Cell Membrane.

We have previously demonstrated that Rad6 and ß -catenin enhance each other's expression through a positive feedback loop to promote breast cancer development/progression. While ß -catenin has been implicated in melanoma pathogenesis, Rad6 function has not been investigated. Here, we examined the relationship between Rad6 and ß -catenin in melanoma development and progression. Eighty-eight cutaneous tumors, 30 nevi, 29 primary melanoma, and 29 metastatic melanomas, were immunostained with anti- ß -catenin and anti-Rad6 antibodies. Strong expression of Rad6 was observed in only 27% of nevi as compared to 100% of primary and 96% of metastatic melanomas. ß -Catenin was strongly expressed in 97% of primary and 93% of metastatic melanomas, and unlike Rad6, in 93% of nevi. None of the tumors expressed nuclear ß -catenin. ß -Catenin was exclusively localized on the cell membrane of 55% of primary, 62% of metastatic melanomas, and only 10% of nevi. Cytoplasmic ß -catenin was detected in 90% of nevi, 17% of primary, and 8% of metastatic melanoma, whereas 28% of primary and 30% of metastatic melanomas exhibited ß -catenin at both locations. These data suggest that melanoma development and progression are associated with Rad6 upregulation and membranous redistribution of ß -catenin and that ß -catenin and Rad6 play independent roles in melanoma development.