Itch in dermatomyositis: the role of increased skin interleukin-31.

BACKGROUND: Interleukin (IL)-31 is implicated in pruritus associated with pruritic skin diseases like atopic dermatitis. Although pruritus is a prominent feature in dermatomyositis (DM), few studies have evaluated the pathogenesis of DM-associated itch. OBJECTIVES: To establish the prevalence of itch in DM, and to investigate the role of IL-31 in DM-related itch. METHODS: Pruritus and disease activity of DM were evaluated by a visual analogue scale (VAS) and the Cutaneous Disease and Activity Severity Index (CDASI), respectively. Expression of IL-31 and IL-31 receptor alpha (IL-31RA) in lesional DM, nonlesional DM and healthy control skin was evaluated by quantitative reverse-transcriptase polymerase chain reaction and immunofluorescence. Flow cytometry was performed on skin cells isolated from lesional DM skin to identify cellular sources of IL-31 in DM. RESULTS: Among 191 patients with DM, 50·8% had moderate-to-severe itch, and itch was correlated with increased cutaneous severity (r = 0·34). In patients with itchy DM, gene expression of IL31 and IL31RA in lesional skin was upregulated compared with nonlesional skin and healthy control skin. IL31 mRNA expression positively correlated with VAS itch score (r = 0·67). On immunofluorescence, immunoreactivity for IL-31 and IL-31RA was stronger in lesional skin. Flow cytometry showed that lesional DM skin contained significantly more IL-31-producing cells, and CD4+ cells were the most common cell type. Lenabasum, an emerging treatment for DM, significantly downregulated IL-31 from CpG-stimulated peripheral blood mononuclear cells. CONCLUSIONS: Increased skin IL-31 may play a role in DM-associated itch, and ongoing trials will evaluate the effects of systemic treatment on IL-31 and itch in DM.

Classification and clinical diagnosis of cutaneous vasculitides.

The definition, diagnostic criteria and classification of systemic vasculitides, of which cutaneous vasculitides (CV) are a part, have long been discussed by the medical scientific world. The most significant contribution is due to the consensus-based criteria specifically derived by the combination of judgments from groups of experts, after accurate literature reviews and developed using consensus techniques. First of them came from the American College of Rheumatology (ACR) in 1990. In 1994 the Chapel Hill International Consensus Conference (CHCC) produced the Consensus-based Criteria essentially providing proper nomenclature for systemic vasculitis, which has been modified in 2012 by the CHCC2012. Moreover, in 2006 European League against Rheumatism and Pediatric Rheumatology European Society produced consensus criteria for the classification of childhood vasculitis. In CHCC2012 CV, affecting small vessels with a predominant skin involvement, have been included in both small vessel vasculitis and single organ vasculitis. The general characteristics of so-called CV have been described (epidemiology, clinical features, histopathology and etiopathogenesis) and, finally, the major characteristics of each clinical type of CV as well as their diagnostic criteria currently available in the literature have been reported.

Acne: a new model of immune-mediated chronic inflammatory skin disease.

Acne is a chronic inflammatory disease of the sebaceous-pilosebaceous unit. Interestingly, inflammation can be detected by histopathological examination and immuohistochemical analysis even in the apparently non-inflammatory acneic lesions, such as comedones. In the last years, it has been clearly demonstrated that acne development is linked to the combination of predisposing genetic factors and environmental triggers, among which a prominent role is played by the follicular colonization by Propionibacterium acnes (P. acnes). P. acnes displays several activities able to promote the development of acne skin lesions, including the promotion of follicular hyperkeratinisation, the induction of sebogenesis, and the stimulation of an inflammatory response by the secretion of proinflammatory molecules and by the activation of innate immunity, that is followed by a P. acnes-specific adaptive immune response. In addition, P. acnes-independent inflammation mediated by androgens or by a neurogenic activation, followed by the secretion in the skin of pro-inflammatory neuropeptides, can occur in acne lesions. In conclusion, acne can be considered as a model of immune-mediated chronic inflammatory skin disease, characterized by an innate immune response that is not able to control P. acnes followed by a Th1-mediated adaptive immune response, that becomes self-maintaining independently from P. acnes itself.

Drug-induced cutaneous vasculitides.

Cutaneous vasculitides (CV) can be idiopathic or secondary to several triggers, including drugs, which account for up to 30% of all the cases of CV. Several drugs can induce CV, including some medications commonly used in dermatology, including minocycline, and several new drugs, such as anti-TNF agents. Different pathomecanisms are involved in the development of drug-induced CV, including the formation and deposition of immune complexes, the induction of neutrophil apoptosis, the formation of neoantigens between the drugs and proteins from the host, the shift of the immune response, and others. Although the diagnosis is difficult, because the clinical picture of drug-induced CV is in general indistinguishable from that of other forms of CV, it is important to recognize such entities in order to correctly manage the patient. Anamnesis, diagnostic algorithms to assess the likelihood of the association between a drug and a cutaneous reaction, skin biopsy and laboratory testing (including the search for antineutrophil cytoplasmic antibodies) are useful tools to make a diagnosis of drug-induced CV. About the therapy, while in idiopathic vasculitides the treatment is usually more aggressive and long-lasting, very often requiring a maintenance therapy with immunosuppressive drugs, in drug-induced CV the discontinuation of the suspected drug alone is usually enough to achieve complete remission, making the prognosis usually very good.

Drug induction in connective tissue diseases.

Connective tissue diseases (CTDs) are defined as a group of acquired disorders resulting from persistent immuno-mediated inflammation. Several classes of drugs seem to be capable of inducing or exacerbating CTDs. A drug-induced (DI) syndrome is defined as a condition temporally related to continuous drug exposure, which resolves upon drug discontinuation. Among CTDs, lupus erythematosus is the most widely known and investigated DI syndrome. However, in recent years, the association between the onset of other CTDs, such as dermatomyositis (DM) and morphea/systemic sclerosis (SSc) has increased in patients with preceding exposure to particular substances. Herein, we conducted a review of published case reports including DM and morphea/SSc, evaluating the real causality among drugs and these syndromes.

The last word on the so-called 'Rowell's syndrome'?

To date, 71 patients having the so-called 'Rowell's syndrome' (RS) have been reported in the literature. However, most of them did not show all the clinical and serological features first described by Rowell and co-workers in 1963. Moreover, since then, subacute cutaneous lupus erythematosus (SCLE) has been identified and the diagnostic criteria as well as the clinical features of erythema multiforme (EM) defined. Accordingly several authors have questioned the existence of RS over the past years. In the present paper, the main clinical, histopathological and immunopathological features of both SCLE and EM are described and all of the cases of RS reported in the literature are also reviewed in depth. A real association between discoid LE and EM was present only in a minority of cases and could be considered a mere coincidence. As for other associations, e.g. those between CLE and lichen planus or psoriasis, the coexistence of CLE and EM does not justify the framing of a separate syndrome as suggested by Rowell et al.

Juvenile psoriatic arthritis and comorbidities: report of a case associated with enthesitis and celiac disease.

The present authors report the case of a 9-year-old boy affected by psoriasis, juvenile psoriatic arthritis, enthesitis, and celiac disease. The signs and symptoms of the different comorbidities appeared at different times in the clinical history, complicating the overall diagnostic and therapeutic procedures. Cooperation between dermatologists and rheumatologist is mandatory in similar cases, where sophisticated technology and teams with specialized and integrated knowledge are required.

Exacerbation of allergic contact dermatitis during immunosuppression with cyclosporine A.

Allergic contact dermatitis (ACD) is one of the commonest occupational diseases in industrialized countries, where it comprises 20-70% of all occupational diseases. Recent studies found out the top ten allergens, but there are some differences in their frequency in relation to gender and age of patients: Myroxylon pereirae and Carba mix resulted the most prevalent allergens in men, while in women the most common sensitizers were nickel sulfate, PPD, fragrance mix and cobalt chloride. ACD is an inflammatory skin disease caused by repeated skin exposure to contact allergens, in which the lesions are due to T CD8+ cells in a type IV, delayed or cell-mediated, immune reaction. The typical skin lesions of ACD in general outburst in contact areas with the specific allergens and they are erythematosus-squamous lesions with other little differences in relation to localization, for example edema, vesicular-exuding lesions or onychodystrophy. Different treatment options exist and are applied according to the severity of the lesions. Topical treatments consist of bland emollients, corticosteroids ointments, topical immunomodulators such as tacrolimus and pimecrolimus ointments, coal tar and derivatives and irradiation with ultraviolet lights or X-rays; while azathioprine, methotrexate, cyclosporine A, oral retinoids or oral corticosteroids represent systemic options of therapy. Nevertheless, the control of chronic ACD is often difficult, overall in patients with chronic ACD.