• IL-36
• acrodermatitis continua of Hallopeau
• generalized pustular psoriasis
• spesolimab
• treatment

• Male
• Humans
• Acrodermatitis/drug therapy
• Acrodermatitis/pathology
• Psoriasis/complications
• Psoriasis/drug therapy
• Psoriasis/pathology
• Skin/pathology
• Biological Products/therapeutic use
• Antibodies, Monoclonal, Humanized

• adalimumab
• adverse drug reaction
• anti-TNF
• chronic recurrent multifocal osteomyelitis
• drug-induced PG
• pustular lesion
• pustular psoriasis
• pyoderma gangrenosum

Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disorder characterized by sudden widespread eruption of superficial sterile pustules with or without systemic inflammation. GPP flares can be life-threatening if untreated due to potential severe complications such as cardiovascular failure and serious infections. Currently, there are no GPP-specific therapies approved in the USA or Europe. Retinoids, cyclosporine, and methotrexate are the most commonly used non-biologic therapies for GPP. The evidence that supports the currently available treatment options is mainly based on case reports and small, open-label, single-arm studies. However, recent advances in our understanding of the pathogenic mechanisms of GPP and the identification of gene mutations linked to the disease have paved the way for the development of specific targeted therapies that selectively suppress the autoinflammatory and autoimmune mechanisms induced during GPP flares. Several biologic agents that target key cytokines involved in the activation of inflammatory pathways, such as tumor necrosis factor-α blockers and interleukin (IL)-17, IL-23, and IL-12 inhibitors, have emerged as potential treatments for GPP, with several being approved in Japan. The evidence supporting the efficacy of these agents is mainly derived from small, uncontrolled trials. A notable recent advance is the discovery of IL36RN mutations and the central role of IL-36 receptor ligands in the pathogenesis of GPP, which has defined key therapeutic targets for the disease. Biologic agents that target the IL-36 pathway have demonstrated promising efficacy in patients with GPP, marking the beginning of a new era of targeted therapy for GPP.

Pustular psoriasis (PP) is a clinicopathological entity encompassing different variants, i.e., acute generalized PP (GPP), PP of pregnancy (impetigo herpetiformis), annular (and circinate) PP, infantile/juvenile PP, palmoplantar PP/palmoplantar pustulosis, and acrodermatitis continua of Hallopeau (ACH), which have in common an eruption of superficial sterile pustules on an erythematous base. Unlike psoriasis vulgaris, in which a key role is played by the adaptive immune system and interleukin (IL)-17/IL-23 axis, PP seems to be characterized by an intense inflammatory response resulting from innate immunity hyperactivation, with prominent involvement of the IL-36 axis. Some nosological aspects of PP are still controversial and debated. Moreover, owing to the rarity and heterogeneity of PP forms, data on prognosis and therapeutic management are limited. Recent progresses in the identification of genetic mutations and immunological mechanisms have promoted a better understanding of PP pathogenesis and might have important consequences on diagnostic refinement and treatment. In this narrative review, current findings in the pathogenesis, classification, clinical features, and therapeutic management of PP are briefly discussed.

• acrodermatitis continua of Hallopeau
• clinical features
• generalized pustular psoriasis
• impetigo herpetiformis
• palmoplantar pustular psoriasis
• palmoplantar pustulosis
• pathogenesis
• pustular psoriasis
• therapy

• Anti-TNF agents
• idiopathic inflammatory myopathy
• juvenile dermatomyositis
• polymyositis
• rituximab

Dermatology complaints account for 3.3% of emergency department (ED) visits per year. Most rashes are benign, but there are a select few that emergency physicians must be familiar with as delay in treatment could be life threatening.

A well-appearing, 76-year-old male presented to the ED with multiple coalescing pustules to his palms and soles and was transferred to the nearest tertiary care hospital for dermatology consult. He was diagnosed with palmoplantar pustulosis and discharged home with a five-day course of clobetasol propionate 0.05% cream twice daily and outpatient dermatology follow-up.

Palmoplantar pustulosis is an uncommon skin condition characterized by recurrent eruptions of sterile pustules localized to the palms and soles. Emergency physician awareness of this rare diagnosis may help prevent hospital admissions and lead to earlier initiation of treatment with outpatient dermatology follow-up.

Targeted immune-modulating treatment with biological agents has revolutionized the management of immune-mediated inflammatory diseases, including rheumatologic conditions. The efficacy and tolerability of biological agents, from the initial tumour necrosis factor (TNF)-α inhibitors to the new anti-cytokine monoclonal antibodies, have dramatically changed the natural history of debilitating conditions such as rheumatoid arthritis and seronegative spondyloarthropathies. The widening use of biologics across several rheumatologic diseases has been associated with a new class of adverse events, the so-called paradoxical reactions. These events are inflammatory immune-mediated tissue reactions, developing paradoxically during treatment of rheumatologic conditions with targeted biologics that are commonly used for treating the idiopathic counterparts of these drug-induced reactions. The skin is frequently involved, and, even if considered rare to uncommon, these cutaneous manifestations are an important cause of biologic agent discontinuation. TNF-α antagonist-induced psoriasis, which can manifest de novo or as exacerbation of a pre-existing form, is the prototypic and most frequent paradoxical skin reaction to biologics while other reactions, such as eczematous and lichenoid eruptions, hidradenitis suppurativa, pyoderma gangrenosum, Sweet’s syndrome and granulomatous skin diseases, occur much more rarely. Management of these reactions consists of topical or systemic skin-directed therapies, depending on the severity and extension of the cutaneous picture, and it is generally associated with switching over to other disease-modifying regimens for treating the underlying rheumatologic condition. Here, we review in detail the current concepts and controversies on classification, pathogenesis and clinical management of this new class of cutaneous adverse events induced by biologics in rheumatologic patients.

• TNFα-inhibitors
• biologics
• paradoxical skin reactions
• psoriasis
• rheumatological disorders

• Pyoderma gangrenosum
• biologics
• small molecules

• Adverse drug events
• Anti-TNF therapy
• Autoimmune disease
• Biologic agents
• Cutaneous vasculitis

• Adult
• Aged
• Antibodies, Monoclonal, Humanized/adverse effects
• Antirheumatic Agents/adverse effects
• Arthritis, Psoriatic/drug therapy
• Arthritis, Rheumatoid/drug therapy
• Certolizumab Pegol/adverse effects
• Erythema/chemically induced
• Erythema/pathology
• Etanercept/adverse effects
• Female
• Humans
• Male
• Middle Aged
• Neutrophils/pathology
• Psoriasis/chemically induced
• Psoriasis/pathology
• Takayasu Arteritis/drug therapy
• Vasculitis, Leukocytoclastic, Cutaneous/chemically induced
• Vasculitis, Leukocytoclastic, Cutaneous/pathology

• Anti-TNF-α
• Golimumab
• Pyoderma gangrenosum
• Rheumatoid arthritis

The use of tumor necrosis factor antagonists (anti-TNF) has become a usual practice to treat various inflammatory diseases. Although indicated for the treatment of psoriasis, anti-TNF may paradoxically trigger a psoriasiform condition. We present a case of a female patient who, during the use of infliximab for rheumatoid arthritis, developed psoriasis. In an attempt to switch anti-TNF class, we observed a cumulative worsening of the lesions requiring suspension of the immunobiological agent and the introduction of other drugs for clinical control. The therapeutic challenge of this paradoxical form of psoriasis is the focus of our discussion. The use of another anti-TNF in these patients is a matter of debate among experts.

• biologics
• drug reactions
• lichen planus
• psoriasis
• tumor necrosis factor-α inhibitors

• Anakinra
• Autoinflammatory
• Biologicals
• CRMO
• Canakinumab
• Cytokine
• Inflammation
• Interleukin-1β
• Osteitis
• TH17
• TNF
• Ustekinumab

• acrodermatitis continua of Hallopeau
• biologic
• generalized pustular psoriasis
• impetigo herpetiformis
• palmoplantar pustulosis
• psoriasis
• pustular psoriasis
• von Zumbusch

• Anti-TNF
• DMARDs (biologic)
• Sarcoidosis
• Treatment

• Anakinra
• Autoinflammatory
• Biologicals
• CRMO
• Canakinumab
• Cytokine
• Inflammation
• Interleukin-1β
• Osteitis
• TH17
• TNF
• Ustekinumab

• Sweet's syndrome
• abatacept
• biologics
• neutrophilic dermatosis
• paradoxical reaction
• rheumatoid neutrophilic dermatosis

Pyoderma gangrenosum (PG) presents with refractory, sterile, deep ulcers most often on the lower legs. Clinically, PG exhibits four types, i.e., ulcerative, bullous, pustular, and vegetative types. PG may be triggered by surgical operation or even by minor iatrogenic procedures such as needle prick or catheter insertion, which is well-known as pathergy. PG is sometimes seen in association with several systemic diseases including rheumatoid arthritis (RA), inflammatory bowel disease, hematologic malignancy, and Takayasu’s arteritis. In particular, various cutaneous manifestations are induced in association with RA by virtue of the activation of inflammatory cells (neutrophils, lymphocytes, macrophages), vasculopathy, vasculitis, drugs, and so on. Clinical appearances of ulcerative PG mimic rheumatoid vasculitis or leg ulcers due to impaired circulation in patients with RA. In addition, patients with PG sometimes develop joint manifestations as well. Therefore, it is necessary for not only dermatologists but also rheumatologists to understand PG.

• Neutrophilic dermatosis
• Pathergy
• Köebner phenomenon
• Autoinflammatory disorder

We performed a systematic search of databases from 1990 to 2013 to identify articles concerning the new onset of dermatomyositis/polymyositis (DM/PM) in patients treated with anti-TNF-α therapy. We retrieved 13 publications describing 20 patients where the new onset of DM/PM after anti-TNF-α therapy was recorded. 17 patients were affected by rheumatoid arthritis (RA), one by Crohn's disease, one by ankylosing spondilytis, and one by seronegative arthritis. In 91% of the cases antinuclear autoantibodies were detected after the introduction of anti-TNF-α therapy. In 6 patients antisynthetase antibodies were detected and other clinical findings as interstitial lung disease (ILD) were recorded. Improvement of DM/PM after anti-TNF suspension (with the concomitant use of other immunosuppressors) was recorded in 94% of cases. The emergence of DM/PM and antisynthetase syndrome seem to be associated with the use of anti-TNF-α agents, especially in patients with chronic inflammatory diseases (mainly RA) with positive autoantibodies before therapy initiation. In particular, physicians should pay attention to patients affected by RA with positive antisynthetase antibodies and/or history of ILD. In those cases, the use of the TNF-α blocking agents may trigger the onset of PM/DM or antisynthetase syndrome or may aggravate/trigger the lung disease.

Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting about 6-10% of patients with cutaneous psoriasis. According to current knowledge, activated T-cells seem to play a pivotal role in the pathogenesis of both psoriasis and PsA. Abatacept is a novel biologic agent selectively designed to interfere with T-cells co-stimulation. Structurally, it is a soluble, fully human fusion protein consisting of the extracellular domain of CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4) linked to a modified Fc portion of human IgG1. Abatacept is now approved as a first-line treatment for rheumatoid arthritis (RA), but preliminary data disclose a potential role of abatacept in the treatment of other autoimmune diseases. In this article, we report a case of successful treatment with abatacept of a psoriatic arthritis patients who developed adverse drug reactions (ADRs) to medication commonly used in PsA, including three different anti-TNF-α agents. In addition, we review the scientific evidences supporting a possible role of abatacept in treatment of patients with psoriasis and PsA and the paradox of abatacept-induced psoriasis.

• Abatacept
• psoriasis
• psoriatic arthritis

Ulcerative colitis and Crohn’s disease are the two forms of inflammatory bowel disease (IBD). The advent of biological drugs has significantly changed the management of these conditions. Skin manifestations are not uncommon in IBD. Among the reactive lesions (immune-mediated extraintestinal manifestations), erythema nodosum (EN) and pyoderma gangrenosum (PG) are the two major cutaneous ills associated with IBD, while psoriasis is the dermatological comorbidity disease observed more often. In particular, in the last few years, anti-tumor necrosis factor (TNF)-α agents have been successfully used to treat psoriasis, especially these kinds of lesions that may occur during the treatment with biological therapies. The entity of the paradoxical manifestations has been relatively under reported as most lesions are limited and a causal relationship with the treatment is often poorly understood. The reason for this apparent side-effect of the therapy still remains unclear. Although side effects may occur, their clinical benefits are undoubted. This article reviews the therapeutic effects of the two most widely used anti-TNF-α molecules, infliximab (a fusion protein dimer of the human TNF-α receptor) and adalimumab (a fully human monoclonal antibody to TNF-α), for the treatment of the major cutaneous manifestations associated with IBD (EN, PG and psoriasis).

• Biological therapies
• Erythema nodosum
• Inflammatory bowel disease
• Psoriasis
• Pyoderma gangrenosum