Martina Burlando

TNF-α gene polymorphisms: Association with disease susceptibility and response to anti-TNF-α treatment in psoriatic arthritis

The tumor necrosis factor-α (TNF-α) gene has been proposed as a major candidate gene in psoriatic arthritis (PsA). TNF-α is a therapeutic target for patients responding poorly to conventional treatments. We investigated the role of single-nucleotide polymorphisms (SNPs) at positions -238, -308, and +489 of the TNF-α gene in the genetic susceptibility to PsA, in the severity of the disease, and, finally, in the response to TNF-α inhibitors (adalimumab, etanercept, or infliximab). Fifty-seven Caucasian PsA patients and 155 healthy matched controls were studied. The SNP +489 variant allele A was significantly associated with PsA susceptibility (P=0.0136) and severity of clinical (Psoriasis Area and Severity Index score, American College of Rheumatology criteria, Disease Activity Score 28, and Disability Index Health Assessment Questionnaire) and laboratory (C-reactive protein and erythrocyte sedimentation rate) parameters (P-values ranging from 0.016 to 2.908 × 10(-12)). The difference in severity was accounted for by the differences between the AA and GA genotypes with respect to the GG genotype. The SNP +489A allele shows a trend of association with the response to PsA treatment with etanercept. These findings suggest a role of the SNP +489A allele in the susceptibility and severity of PsA.

Atypical presentations of bullous pemphigoid: Clinical and immunopathological aspects

Bullous pemphigoid may occur in extremely variegated manners, misleading even experienced dermatologists. Indeed the type and/or distribution of lesions may be unusual. Furthermore, there may be an atypical demographic profile of patients, a different clinical course and a different responsiveness to therapy. Up to 20% of the cases the onset is characterized by a non-bullous phase, lasting weeks, months or in particular cases remaining the only manifestation of the disease. During this early phase lesions are generally pruritic erythematous, eczematous or urticarial; however, lesions may also resemble polycyclic, targetoid, nodular or lichenoid lesions. These atypical lesions may also coexist with typical bullae. Other atypical presentations include a vesicular eruption and an erythroderma. Manifestations in children differ from adult forms, presenting an exclusive genital involvement in 50% of cases or a preponderant involvement of the face, the palms and the soles. Rarely bullous pemphigoid is confined to certain body areas, due to particular triggering factors or to a lower disease activity. Therefore, the need to formulate universally recognized diagnostic criteria is increasingly evident, especially for atypical bullous pemphigoid. Direct immunofluorescence of perilesional skin and detection of circulating autoantibodies are mandatory in the diagnosis, especially when the clinical presentation is doubtful.

Papular elastolytic giant cell granuloma: report of a case associated with monoclonal gammopathy and responsive to topical tacrolimus

Papular elastolytic giant cell granuloma is an unusual variant of annular elastolytic giant cell granuloma. Its rarity makes the assessment of the real efficacy of any treatment difficult, as spontaneous remission is possible. We report a case whose interest, besides the rarity of the occurrence, rests in the pure papular expression of the clinical features, the association with a monoclonal gammopathy and the apparent efficacy of topical tacrolimus.

Adverse Effects of Biological Agents in the Treatment of Psoriasis

Tumour necrosis factor (TNF) antagonists are generally well tolerated, but carry the risk of side effects. In patients with psoriasis, the potential risks with anti-TNF agents may be overestimated because the most commonly reported adverse events are based on studies in patients with rheumatoid arthritis or inflammatory bowel disease. Whereas patients with psoriasis typically receive monotherapy, these patients are treated with biological-based combination therapies. Furthermore, patients with psoriasis have distinctive and different comorbidities, which could play a role in the development of different adverse events. However, the potential risks of the use of biological agents should always be taken into consideration

Specific autoantibodies in dermatomyositis: a helpful tool to classify different clinical subsets

Autoantibodies are important in the diagnosis of dermatomyositis. They can be divided in two different groups: myositis-associated autoantibodies (MAA) prevailing in overlap syndromes, and myositis-specific autoantibodies (MSA), with diagnostic specificity exceeding 90%. Our purpose was to detect retrospectively the prevalence of the most common MSAs in a group of 19 adult DM patients (13 women, 6 men). A severe DM (SDM), with extensive cutaneous and muscular manifestations, dysphagia, and sometimes pneumopathy, was detected in ten cases. Three patients had a mild DM (MDM), with little muscle and skin impairment, and a short course. Four patients suffered from amyopathic DM (ADM), two from paraneoplastic DM (PDM). Each serum was tested for ANA, ENA, MAAs, MSAs. Myositis-specific autoantibodies were detected in 15 cases. The most frequent was anti-TIF1γ, associated with SDM or PDM in four out of seven cases. Anti-MDA5 antibodies were recorded in a SDM and in a ADM with lung fibrosis. Anti-Mi2 and anti-SRP antibodies were both detected in a MDM and in a SDM, whereas anti-SAE1 in a amyopathic form. Other antibodies (anti-NXP2, -Jo1, -PL7, -PL12, -OJ) were found in single patients with SDM. Our series confirmed that specific autoantibodies could be helpful to classify different clinical subsets, particularly in the case of paraneoplastic forms or association with pneumopathy. Moreover, they can help in predicting the disease evolution and influence therapeutic strategies. A greater number of cases should be useful to highlight the clinical and pathogenic role of these antibodies, and develop a homogeneous protocol for diagnosis and treatment.

Autoantibody Profile of a Cohort of 78 Italian Patients with Mucous Membrane Pemphigoid: Correlation Between Reactivity Profile and Clinical Involvement

Direct diagnosis of mucous membrane pemphigoid (MMP) is not easy. Circulating autoantibodies targeting bullous pemphigoid antigens of 180 kDa and 230 kDa (BP180 and BP230), α6β4 integrin, laminin 332 and type VII collagen (Col VII) are not always present. The aims of this study were to characterize the humoral immune response of a cohort of Italian patients with MMP, its association with clinical involvement and severity, and to design an algorithm for efficient serological diagnosis. Seventy-eight MMP sera were studied retrospectively by indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Indirect immunofluorescence on salt-split skin resulted in the most sensitive approach for diagnosis of MMP. BP180 was the major autoantigen in MMP patients with oral and cutaneous involvement. Significant associations were found between BP180 reactivity and oral and cutaneous localization of the lesions (p = 0.006), and between Col VII positivity and Setterfield severity score (p = 0.020).

Cutaneous Drug Eruption with an Interface Dermatitis Pattern due to Anti-tumour Necrosis Factor-alpha Agents: A Relevant Class-effect

© 2010 The Authors. doi: 10.2340/00015555-0839 Journal Compilation

Ciprofloxacin as a trigger for bullous pemphigoid: The second case in the literature

Drug-induced bullous pemphigoid (DIBP) has been reported to be an autoimmune bullous disease induced or precipitated by several drugs, immunopathologically similar to classic bullous pemphigoid. Several medications may not only cause DIBP, including diuretics, antiarrythmics-antihypertensives, and recently antitumor necrosis factor agents, other drugs as chloroquine, but also rarely by antibiotics as amoxicillin and penicillin. The authors present the third case of DIBP induced by quinolones and the second case of localized DIBP triggered by oral ciprofloxacin. A DIBP can be suspected in old patients when they add or change some drugs in their normal medication regimen.

Generalized annular granuloma associated with crowned dens syndrome, which resolved with colchicine treatment

Granuloma annulare (GA) is a chronic, benign, and usually self‐limiting cutaneous inflammatory disease, typically characterized by small, localized, skin‐coloured papules that are usually asymptomatic or mildly pruriginous. Its aetiopathogenesis is still unknown and treatments are rarely effective. Generally, 50–70% of localized GA cases are self‐limiting and show spontaneous resolution after 1–2 years, whereas disseminated GA is less likely to disappear without treatment. Treatment of generalized GA is usually based on single case reports, and only a few studies involving large case series have been published. We present the case of a patient affected by generalized GA, which resolved after colchicine treatment used for concomitant crowned dens syndrome due to calcium pyrophosphate deposition disease (CPPD). Colchicine may have worked by a direct action on GA or, alternatively, by controlling CPPD, as a possible trigger. As the low‐dosage colchicine treatment was well tolerated by our patient, this could be easily used in the management of GA. However, further studies are needed to confirm the action of colchicine on GA.

Psoriasis as a cardiovascular risk factor: updates and algorithmic approach

Although psoriasis is predominantly a chronic inflammatory skin disorder, it has been known to be associated with cardiovascular disease. Patients with psoriasis, particularly with moderate to severe forms, present an increased rate of cardiovascular mortality, myocardial infarction and stroke. However the pathophysiology of the relationship between psoriasis and cardiovascular risk and comorbidities has not yet completely known. Chronic inflammation may be considered a solid link between psoriasis and related cardiovascular events. Several cytokines and inflammatory cells play a pivotal role in the development of psoriatic lesions, resulting in angiogenesis and endothelial dysfunction. Furthermore, the imbalance between oxidative stress and antioxidant mechanisms in psoriatic patients may contribute to explain the pathogenesis of increased reactive oxygen species and the formation of atherosclerotic plaque. Other mechanistic pathways which may be involved in this relationship include cardiovascular effects of medications, a common genetic background and a higher prevalence of cardiovascular risk factors, which are often under-diagnosed and under-treated in psoriatic patients. Indeed, the early detection of specific markers of cardiovascular impairment, such as N-terminal pro B-type natriuretic peptide, homocysteine and YKL-40, may enable psoriatic patients at higher cardiovascular risk to be identified as soon as possible. This review examines the increased cardiovascular risk profile and high prevalence of cardiovascular disease associated with psoriasis, focusing on pathogenic links between psoriasis and atherosclerosis, serological markers of cardiovascular involvement and the implications of antipsoriatic therapies on cardiovascular risk and proposes a flow chart, that every dermatologist should follow to screen psoriatic patients.