Skin cancer risk in people living with HIV: a call for action.

A diagnosis of HIV poses secondary medical risks to patients, ranging from infections to neoplastic conditions. Regarding skin cancer, these risks extend beyond the well known association with Kaposi sarcoma and include Merkel cell carcinoma, squamous cell carcinoma, and high-risk melanomas. Despite evidence of these risks, knowledge and awareness remain low, among care providers for people living with HIV, individual patients, and even some specialists in dermatology. Crucially, medical organisations do not adequately address this concern, as there is an absence of treatment guidelines for the screening and management of skin cancer for people living with HIV. To continue providing high-quality care for this population, the increased risk of multiple high-risk skin cancers needs to be appropriately recognised by both providers and patients. Accordingly, we call for renewed emphasis on patient education and implementation of improved organisational guidelines for skin cancer screening protocols.

Biologic Therapies in HIV/AIDS Patients with Inflammatory Diseases: A Systematic Review of the Literature.

Biologic therapies have been increasingly developed and used for the treatment of severe inflammatory diseases. However, the safety and efficacy profile of biologic drugs in patients with HIV is not well established as this patient population is historically excluded from clinical trials. We review the available evidence of biologic use in people with HIV. We conducted a systematic review of the literature up to June 29, 2022 and included studies that treated patients with HIV who have inflammatory disease using biologic drugs. Clinical data regarding safety and efficacy were abstracted into tables. One hundred twelve studies were included, and 179 patients were included in our study. Nearly all classes of biologics drugs had a favorable safety profile with minimal or minor adverse events. Anti-CD-20 inhibitors and TNF-alpha inhibitors were associated with opportunistic infections. Transient increase in HIV viral load was noted with use of some agents such as TNF-alpha inhibitors. The quality of evidence is low, restricted to case reports and retrospective reviews. However, the safety profile of biologics observed in these patients with HIV was overall favorable.

What's new in HIV dermatology?

HIV has long been associated with a number of inflammatory, infectious, and neoplastic skin conditions. In the era of anti-retroviral therapy, we have discovered even more about the relationship between skin disease and chronic immunosuppression. In particular, clinicians still face the propensity of persons living with HIV to develop difficult-to-control viral infections, chronic skin inflammation, and pruritus and-particularly as patients age-various types of skin cancers. Here, we summarize recent updates in the field of HIV dermatology and make recommendations to providers caring for these patients.

Hidradenitis Suppurativa: A Guide for the Practicing Physician.

Hidradenitis suppurativa is a chronic inflammatory disease of apocrine gland-bearing skin. Although immunologic derangements, genetic predisposition, obesity, and smoking are likely important factors, the pathogenesis of the disease and the effect of available treatments on disease course have not been fully elucidated. In the absence of proper treatment, chronic inflammation results in diffuse scarring and a wide array of complications, including the development of cutaneous squamous cell carcinoma. This severe and chronic disease can have detrimental effects on self-esteem and quality of life. No ideal treatment regimen has been defined, but several therapies have been found to reduce lesion severity and improve symptoms. We reviewed the literature through July 2014 for existing treatments. Published articles were obtained via systematic review of medical databases (PubMed, Embase, Google Scholar) and scrutiny of citation lists using the search terms "hidradenitis suppurativa" and "acne inversa". Given the scarce literature on treatment strategies, we also reviewed data from any case reports or prospective and retrospective studies that were located. On the basis of the existing literature, we provide an evidence-based algorithm for the management of this disease in the primary care setting. More research is needed to evaluate the comparative effectiveness of topical and systemic treatments and to better understand the pathogenesis, natural history, and subtypes of hidradenitis suppurativa.

Cutaneous manifestations of ESRD.

A broad range of skin diseases occurs in patients with ESRD: from the benign and asymptomatic to the physically disabling and life-threatening. Many of them negatively impact on quality of life. Their early recognition and treatment are essential in reducing morbidity and mortality. The cutaneous manifestations can be divided into two main categories: nonspecific and specific. The nonspecific manifestations are commonly seen and include skin color changes, xerosis, half-and-half nails, and pruritus. The specific disorders include acquired perforating dermatosis, bullous dermatoses, metastatic calcification, and nephrogenic systemic fibrosis. This review article describes these conditions and considers the underlying pathophysiology, clinical presentations, diagnosis, and treatment options.

An open-label study of anakinra for the treatment of moderate to severe hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by sterile abscesses and fistulae predominantly affecting the axillae and groin. Various biologic agents have been attempted for HS, but there is still no definitive treatment. OBJECTIVES: We sought to evaluate the efficacy, safety, and tolerability of anakinra in the treatment of moderate to severe HS. METHODS: Six patients with moderate to severe HS were enrolled in an open-label study with all patients receiving active treatment for 8 weeks with an additional 8 weeks of follow-up off therapy. RESULTS: The 5 patients who completed the 8-week therapy showed a significant mean decrease in their modified Sartorius score of 34.8 points. The physician and patient global assessment of overall activity showed significant reductions between baseline and 8 weeks of therapy: 45.8 points and 35.6 points, respectively. The Dermatology Life Quality Index showed a significant reduction after 8 weeks of treatment with anakinra. Functional T-cell analysis revealed that patients had increased percentages of CD3(+) T cells in lesional skin compared with nonlesional skin before therapy. LIMITATIONS: The limited number of patients and lack of control group are limitations. CONCLUSIONS: Anakinra demonstrated decreased HS disease activity by both objective and subjective measures.

Neutrophilic urticaria with systemic inflammation: a case series.

IMPORTANCE: Predominantly neutrophilic infiltrates are seen in a subset of patients with urticaria. The lesions tend to be less itchy and poorly responsive to standard therapy, including antihistamines. We describe 2 patients having neutrophilic urticaria with systemic inflammation (NUSI) without known connective tissue disorder or malignancy. We propose the term NUSI to help classify a previously undefined multisystemic inflammatory entity likely mediated by interleukin 1 (IL-1). OBSERVATIONS: Patient 1, a 47-year-old woman, was seen with urticaria and associated night sweats, fevers, and polyarticular arthritis. Acute-phase reactants were elevated with worsening of symptoms. Initial treatment with a combination of topical and systemic corticosteroids, antihistamines, and immunosuppressants was unsuccessful. A 100% clinical resolution was achieved with anakinra, an IL-1 receptor antagonist. Patient 2, a 24-year-old woman, was seen with urticaria and associated joint pain and swelling. Initial treatment included a combination of antihistamines, colchicine, and dapsone. Only colchicine provided moderate benefit but was stopped because of significant gastrointestinal tract discomfort. Anakinra was initiated; the patient achieved 100% control while receiving daily therapy. CONCLUSIONS AND RELEVANCE: The diagnosis of NUSI is important to consider in patients who are seen with antihistamine-resistant urticaria in combination with systemic inflammatory symptoms. Interleukin 1 blockade is a viable option for therapy.

Melanoma death prevention: moving away from the sun.

This evidence-backed editorial addresses the limitations of solely primary prevention campaigns and outlines the proven efficacy of early detection/secondary prevention strategies with respect to melanoma. It synthesizes experience from several outreach efforts that have resulted in sustained improvements in knowledge and self-skin examination behaviors. Data demonstrate that educational campaigns emphasizing increased knowledge about melanoma and self-screening practices correlate with thinner tumors. The editorial also confronts the lack of data around skin cancer screening per the US Preventative Services Task Force. It explains how we might address the issue to obtain solid evidence to back a recommendation for screening of high-risk populations in the future. Cost-efficacy of skin cancer screening is also addressed. Lastly, lessons learned from other cancers, particularly breast cancer, with respect to successful educational campaign creation and development of an effective cause marketing campaign for advocacy are discussed. Hypothetical ideas for a screening algorithm and for educational/media campaigns are presented with the hope of triggering thoughtful discussion and forward momentum.

Autoinflammation: From monogenic syndromes to common skin diseases.

Autoinflammation is characterized by aberrant regulation of the innate immune system and often manifests as periodic fevers and systemic inflammation involving multiple organs, including the skin. Mutations leading to abnormal behavior or activity of the interleukin 1 beta (IL-1ß)-processing inflammasome complex have been found in several rare autoinflammatory syndromes, for which anticytokine therapy such as IL-1 or tumor necrosis factor-alfa inhibition may be effective. It is becoming clear that features of autoinflammation also affect common dermatoses, some of which were previously thought to be solely autoimmune in origin (eg, vitiligo, systemic lupus erythematosus). Recognizing the pathogenetic role of autoinflammation can open up new avenues for the targeted treatment of complex, inflammatory dermatoses.

Immunosenescence is associated with presence of Kaposi's sarcoma in antiretroviral treated HIV infection.

OBJECTIVE: Some antiretroviral treated HIV-infected patients develop Kaposi's sarcoma despite long-term suppression of HIV replication. These Kaposi's sarcoma lesions are consistent with Kaposi's sarcoma observed in the elderly uninfected population ('classical Kaposi's sarcoma'). We investigated potential mechanisms for this phenomenon, focusing on measures of immune activation and T-cell senescence. DESIGN: We compared markers of immunosenescence, naive T cells, activation, and inflammation in CD4+ and CD8+ T cells from antiretroviral-treated participants with new-onset Kaposi's sarcoma (cases, n =  19) and from treated individuals without Kaposi's sarcoma (controls, n  = 47). RESULTS: There was increased frequency of CD4+ and CD8+ T cells with an immunosenescence phenotype (CD57+ and CD28-) in cases vs. controls (CD4+ T cells: CD57+ 7.4 vs. 3.7%, P = 0.025; CD28- 9.1 vs. 4.8%, P  = 0.025; CD8+ T cells: CD57+ 41.5 vs. 27.7%, P  =  0.003; CD28- 60.5 vs. 51.3%, P  = 0.041). Cases had lower proportions of naïve T cells (CD27+ CD28+ CD45RA+) in CD4+ (23.0 vs. 32.2%, P = 0.023) and CD8+ (11.3 vs. 20.7%, P  <  0.001) T-cell compartments. CCR5 was more highly expressed in CD4+ (16.3 vs. 11.0%, P  = 0.025), and CD8+ (43.1 vs. 28.3%, P < 0.001) T-cell compartments in cases vs. controls. There was no difference in telomere length or telomerase activity in peripheral blood mononuclear cells, or in T-cell expression of activation markers (HLADRCD38). CONCLUSION: Among antiretroviral-treated patients, increased frequencies of T cells with an immunosenescence phenotype and lower frequencies of naive T cells were associated with presence of Kaposi's sarcoma among effectively treated patients. These data suggest that certain immunologic perturbations--including those associated with aging--might be causally associated with development of Kaposi's sarcoma.

Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study.

INTRODUCTION: To assess the effect of canakinumab, a fully human anti-interleukin-1ß antibody, on symptoms and health-related quality of life (HRQoL) in patients with cryopyrin-associated periodic syndrome (CAPS). METHODS: In this 48-week, phase 3 study, patients with CAPS received canakinumab 150 mg subcutaneously at 8-week intervals. All patients (n = 35) received canakinumab during weeks 1 through 8; weeks 9 through 24 constituted a double-blind placebo-controlled withdrawal phase, and weeks 24 through 48 constituted an open-label phase in which all patients received canakinumab. Patient and physician assessments of symptoms, levels of inflammatory markers, and HRQoL were performed. RESULTS: Rapid symptom remission was achieved, with 89% of patients having no or minimal disease activity on day 8. Responses were sustained in patients receiving 8-weekly canakinumab. Responses were lost during the placebo-controlled phase in the placebo group and were regained on resuming canakinumab therapy in the open-label phase. Clinical responses were accompanied by decreases in serum levels of C-reactive protein, serum amyloid A protein, and interleukin-6. HRQoL scores at baseline were considerably below those of the general population. Improvements in all 36-item Short-Form Health Survey (SF-36) domain scores were evident by day 8. Scores approached or exceeded those of the general U.S. population by week 8 and remained stable during canakinumab therapy. Improvements in bodily pain and role-physical were particularly marked, increasing by more than 25 points from baseline to week 8. Therapy was generally well tolerated. CONCLUSIONS: Canakinumab, 150 mg, 8-weekly, induced rapid and sustained remission of symptoms in patients with CAPS, accompanied by substantial improvements in HRQoL. TRIAL REGISTRATION: Clintrials.gov NCT00465985.

Skin infections in HIV-infected individuals in the era of HAART.

PURPOSE OF REVIEW: Clinicians should be aware of the shift in the cutaneous infectious disease burden in human immunodeficiency virus-infected individuals as a reflection of immune restoration in the era of highly active antiretroviral therapy (HAART). RECENT FINDINGS: As in the general population but to greater extent, methicillin-resistant Staphylococcus aureus (MRSA) soft-tissue infection is a rising problem among those with human immunodeficiency virus (HIV). Human papilloma virus (HPV) is exceedingly prevalent and persistent despite HAART, and HPV-associated malignancy is increasing as those with HIV live longer. Herpes, syphilis, and Kaposi's sarcoma continue to plague individuals with HIV. Immune reconstitution inflammatory syndrome (IRIS) is common and often presents with infectious cutaneous manifestations. SUMMARY: This review implicates the importance of the acknowledgment of MRSA infections risk factors, screening for HPV-related neoplasia, continuance of trials to establish the efficacy of herpes vaccines, and awareness of prevalent cutaneous infections presenting with IRIS in those with HIV.

Cryopyrin-associated periodic syndrome: an update on diagnosis and treatment response.

Cryopyrin-associated periodic syndrome (CAPS) is a rare hereditary inflammatory disorder encompassing a continuum of three phenotypes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and neonatal-onset multisystem inflammatory disease. Distinguishing features include cutaneous, neurological, ophthalmologic, and rheumatologic manifestations. CAPS results from a gain-of-function mutation of the NLRP3 gene coding for cryopyrin, which forms intracellular protein complexes known as inflammasomes. Defects of the inflammasomes lead to overproduction of interleukin-1, resulting in inflammatory symptoms seen in CAPS. Diagnosis is often delayed and requires a thorough review of clinical symptoms. Remarkable advances in our understanding of the genetics and the molecular pathway that is responsible for the clinical phenotype of CAPS has led to the development of effective treatments. It also has become clear that the NLRP3 inflammasome plays a critical role in innate immune defense and therefore has wider implications for other inflammatory disease states.

Hidradenitis suppurativa and concomitant pyoderma gangrenosum: a case series and literature review.

BACKGROUND: Hidradenitis suppurativa (HS) and pyoderma gangrenosum (PG) are both rare inflammatory skin conditions that are associated with systemic inflammatory diseases. We performed a retrospective medical chart review of patients with an overlap of HS and PG. OBSERVATIONS: We identified 11 cases of PG lesions presenting in patients with HS. Ten of the patients were women, and 9 were obese. All the patients developed HS lesions first, a median of 2.5 years (range, 0-15 years) preceding the appearance of PG lesions. All patients required multiple therapeutic agents because their diseases were often poorly responsive to standard therapies. Two patients received tumor necrosis factor inhibitors; 1 responded to treatment. One patient was treated with anakinra (interleukin-1 receptor antagonist) and had a 75% improvement of her lesions. CONCLUSIONS: We have identified a group of patients who have an overlap of PG and HS. Pyoderma gangrenosum can appear at any point after the development of HS and often has a severe, refractory course. We propose that PG and HS may represent variant manifestations of cytokine dysregulation by the innate immune system with common etiology. New therapeutic agents are eagerly sought, and further investigation with regard to interleukin 1 blockade is warranted.

Narrowband ultraviolet B phototherapy is beneficial in antihistamine-resistant symptomatic dermographism: a pilot study.

BACKGROUND: Symptomatic dermographism is the most common type of physical urticaria. It can be severe and poorly controlled with H1 antihistamines in some patients. Photochemotherapy (psoralen plus ultraviolet [UV] A) may help the itch of dermographism but the effect of narrowband (NB) UVB therapy has not been previously studied. OBJECTIVES: We sought to examine the clinical efficacy of NB UVB therapy for itch and whealing in symptomatic dermographism and to assess the duration of the effect during 3 months of follow-up. METHODS: Eight patients (6 female) were enrolled into an open uncontrolled prospective study. Intensity of itching and whealing was assessed with visual analog scales and the whealing response was evaluated by testing with a dermographometer at pressures of 20, 36, and 60 g/mm2 on the upper aspect of the back. NB UVB phototherapy was given for 6 weeks 3 times weekly starting at 50% of minimal erythema dose with 20% to 0% increments as tolerated. Fexofenadine (180 mg/d) was taken during the run-in period and subsequently throughout the study and follow-up as required. Patients were followed for 3 months with regular assessments every 6 weeks after completion of phototherapy. RESULTS: All patients showed an improvement in itching at the end of NB UVB treatment (mean [SD] reduction 52.3% [31.6%]). Subjective assessment of whealing revealed a significant improvement in all but two patients (mean [SD] reduction 71% [54%]). There was a small and statistically significant improvement in cumulative dermographometer-induced wheal widths at the end of phototherapy (P = .038). A time trend for the relapse of symptoms within 12 and 18 weeks after completing phototherapy was significant for both visual analog scale scores but not for dermographometer-induced whealing. LIMITATIONS: The apparent rarity of antihistamine-resistant symptomatic dermographism limited the study to a small number of participants. The severity of the condition did not permit a controlled and blinded study design. CONCLUSIONS: NB UVB phototherapy is an effective second-line treatment for patients with severe symptomatic dermographism responding poorly to fexofenadine. This therapy can lead to subjective relief of pruritus and whealing and objective reduction of whealing. NB UVB phototherapy may restore symptom control with antihistamines in some patients.

Phenotype, genotype, and sustained response to anakinra in 22 patients with autoinflammatory disease associated with CIAS-1/NALP3 mutations.

OBJECTIVE: To characterize the multisystem chronic inflammatory phenotype, dermatopathologic features, and response to therapy with interleukin 1 receptor antagonist (anakinra) in patients with mutations in the CIAS-1/NALP3 gene. DESIGN: Retrospective review of medical records and evaluation of histologic findings. SETTING: The National Amyloidosis Centre, London, and a tertiary referral clinic for urticaria. PATIENTS: Twenty-two individuals from 13 families with autoinflammatory disease associated with CIAS-1/NALP3 mutations. MAIN OUTCOME MEASURES: Phenotype, genotype, skin histologic findings, and response to treatment with anakinra. RESULTS: Five heterozygous missense mutations were identified in CIAS-1/NALP3. Skin histologic findings revealed marked vascular dilatation and neutrophilic infiltration involving small vessels and eccrine glands. Serologic evidence of intense inflammation was present in untreated patients, with median serum amyloid A protein and C-reactive protein levels of 141 and 38 mg/L, respectively. Fifteen patients received anakinra for up to 39 months, all of whom achieved serologic remission and complete resolution of fever, rash, conjunctivitis, and rheumatic symptoms, without any adverse effects. Six patients had AA (reactive systemic) amyloidosis, 2 of whom died of renal failure complications before interleukin 1-inhibiting therapy was available; 1 patient underwent renal transplantation and remains clinically well taking anakinra, and in the remaining 3 patients, anakinra therapy resulted in remission of their nephrotic syndrome. CONCLUSIONS: Anakinra therapy was well tolerated and has sustained efficacy on dermatologic and rheumatic manifestations in these patients with CIAS-1/NALP3 mutations. This treatment also resulted in resolution of AA amyloidosis-associated nephrotic syndrome in all affected patients.