Donatella Schena

Drug-induced lupus erythematosus

Drug-induced lupus erythematosus (DILE) is defined as a lupus-like syndrome temporally related to continuous drug exposure which resolves after discontinuation of the offending drug. There are currently no standard diagnostic criteria for DILE and the pathomechanisms are still unclear. Similarly to idiopathic lupus, DILE can be diveded into systemic (SLE), subacute cutaneous (SCLE) and chronic cutaneous lupus (CCLE). Systemic DILE is characterized by typical lupus-like symptoms including skin signs, usually mild systemic involvement and a typical laboratory profile with positive antinuclear and anti-histone antibodies, while anti-double strand (ds) DNA and anti-extractable nuclear antigens antibodies are rare. High risk drugs include hydralazine, procainamide and isoniazid. Drug-induced SCLE is very similar to idiopathic SCLE in terms of clinical and serologic characteristic, and it is more common than the systemic form of DILE. Drugs associated with SCLE include calcium channel blockers, angiotensin-converting enzyme inhibitors, interferons, thiazide diuretics and terbinafine. Drug-induced CCLE is very rarely reported in the literature and usually refers to fluorouracile agents or non steroidal anti-inflammatory drugs. Recently, cases of DILE have been reported with anti-TNFα agents. These cases present with disparate clinical features including arthritis/arthralgia, skin rash, serositis, cytopenia and variable laboratory abnormalities. DILE to anti-TNFα agents differs in several ways to classic DILE. The incidence of rashes is higher compared to classical systemic DILE. In most cases of classic DILE visceral involvement is rare, whereas several cases of anti-TNFα DILE with evidence of renal disease have been reported. Low serum complement levels as well as anti-extractable nuclear antigen antibodies and anti-dsDNA antibodies are rarely present in classic DILE, whereas they are reported in half the cases of anti-TNFα DILE; in contrast, anti-histone antibodies are described in classic DILE more often than in anti-TNFα DILE. Recognition of DILE in patients receiving anti-TNFα therapy can be difficult due to the symptoms of their underlying disease. A temporal association (months to years) of the offending drug with characteristic or suggestive symptoms, and resolution of symptoms on drug withdrawal is the best evidence for this diagnosis of DILE.

Family history, smoking habits, alcohol consumption and risk of psoriasis

Summary We have conducted a multicentre case‐control study to assess the epidemiological importance of previously suggested risk factors for psoriasis, including family history of the disease, smoking and alcohol consumption. Newly diagnosed psoriatics, with a history of skin manifestations no longer than 2 years were eligible as cases; as controls we selected subjects with newly diagnosed dermatological conditions other than psoriasis. Interviews were performed by trained medical investigators using a structured questionnaire. Two‐hundred and fifteen cases, aged 16–65 years (median age 38), and 267 controls, aged 15–65 years (median age 36), were interviewed and included in the analysis. Family history was a risk factor for psoriasis; the multiple logistic regression (MLR) adjusted‐odds ratio was 18.8 (95% confidence interval 6.4–54.8) for a history in parents, and 3.2 (95% confidence interval 1.5–6.6) for a history in siblings. The risk of psoriasis was higher for current smokers than for those who had never smoked. The MLR adjusted odds ratio was 2.1 (95% confidence interval 1.1–4.0) for people smoking 15 cigarettes or more per day. The risk of psoriasis was higher for alcohol drinkers: compared with teetotallers the MLR adjusted‐odds ratios were 1.3 (95% confidence interval 0.8–2.3) for subjects drinking one or two drinks/day and 1.6 (95% confidence interval 0.9 to 3.0) for those drinking three or more. However, the trend in risk was not statistically significant. Our study confirms the role of family history in psoriasis and provides some evidence of a dose‐response relationship for an association between smoking habits and psoriasis.

Risk of nonmelanoma skin cancer in Italian organ transplant recipients. A registry-based study.

Background. Organ transplant recipients are at an increased risk of nonmelanoma skin cancer.Few data concern heart transplantation and populations from southern Europe. Methods. A total of 1329 patients who received their first kidney (1062 subjects) or heart allograft (267 subjects) were included in a partly retrospective cohort study to evaluate the risk of skin cancer. The incidence rate per 1000 person-years and the cumulative incidence were computed. Standardized morbidity ratio was estimated by comparison with Italian cancer registry data. To analyze the role of potential prognostic factors, Cox’s regression method was used. Results. The overall incidence rate of nonmelanoma skin cancer was 10.0 cases per 1000 posttransplant person-years (95% confidence interval 8.2–11.7). This estimate was far higher than expected in the general population. The overall risk of developing skin cancer increased from a cumulative incidence of 5.8% after 5 posttransplant years to an incidence of 10.8% after 10 years of graft survival. In a Cox proportional hazard risk model, the most important factors that appeared to favor the development of skin cancer were age at transplantation and sex. After adjustment for age at transplantation and sex, no definite increased risk was documented among heart as compared with kindney transplant recipients. Conclusions. Our study confirms the increased risk of nonmelanoma skin cancer among organ transplant recipients in a southern European population.

Expression of cytokines and chemokine receptors in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis

Background  Erythema multiforme (EM) and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are caused by a dysregulation of cellular immunity.

Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis

OBJECTIVE We systematically assessed bone mineral density (BMD), bone turnover markers (BTM), and fractures in a large cohort of patients with Indolent Systemic Mastocytosis (ISM). METHODS Eighty-two patients (mean age 48 years, 37 women) with ISM were studied. BMD was measured by dual X-ray absorptiometry at the lumbar spine and proximal hip. The serum markers of bone turnover included bone-specific alkaline phosphatase, C-telopeptides of type I collagen, and serum osteocalcin. Previous clinical fractures were registered and spine X-ray was obtained from all patients. RESULTS Three women were excluded for concomitant diseases associated to osteoporosis. Osteoporosis according with the WHO classification (T-score<-2.5) was found in 16 patients (20.0%) (7 females and 9 men). Mastocytosis-related low BMD (Z-score at either the spine or the hip<-2) was found in 3 women (9%) and 13 men (28%). The BMD was generally lower at the spine than at the hip. No significant correlation was observed between serum tryptase levels and T or Z-score BMD. One or more moderate or severe vertebral fractures were found in 17 patients (12 men); in 11 of them Z-score values were>-2 or not valuable at the spine. No significant difference was found in the prevalence of mastocytosis-related low BMD and/or vertebral fractures between patients with or without skin involvement. Two patients had radiographic and densitometric osteosclerosis-like characteristics. In osteoporotic patients higher, normal or lower serum BTM were found, without correlations with serum tryptase levels, while in patients with osteosclerosis both BTM and serum tryptase values were particularly increased. CONCLUSIONS Vertebral osteoporosis and fractures are frequent in patients with ISM. Spine X-ray and densitometric examination are warranted in all patients, also without skin involvement and particularly in males; Z-score other than T-score BMD must be evaluated. Patients with idiopathic osteoporosis should be evaluated for mast cell disease. Both high than low BTM can be observed in patients with osteoporosis while osteosclerosis is characterized by high bone turnover and serum tryptase levels.

Interstitial granulomatous dermatitis: a distinct entity with characteristic histological and clinical pattern.

Background  Interstitial granulomatous dermatitis (IGD) is a rare disease for which a clinical–pathological correlation is essential to establish diagnosis.

The CD40/CD40 ligand system is expressed in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum.

Background  Erythema multiforme (EM) and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are determined by a dysregulation of cellular immunity.

Urticarial lesions: If not urticaria, what else? The differential diagnosis of urticaria Part I. Cutaneous diseases

UNLABELLED Acute urticaria is self-limiting, and a cause can be identified in many patients. Chronic urticaria is a long lasting disease, and patients are commonly examined for an autoimmune origin and for associated diseases. Although the diagnosis of urticaria is straightforward in most patients, it may pose some difficulties at times and it may require a careful differential diagnosis with a number of conditions. Urticarial syndromes comprise both cutaneous and systemic disorders. Part I of this two-part series focuses on the clinical and histologic features that characterize common urticaria and on the cutaneous diseases that may manifest with urticarial lesions and must be considered in the differential diagnosis. LEARNING OBJECTIVES After completing the learning activity, participants should be able to distinguish between the typical wheals of urticaria and urticarial lesions suggesting other diagnoses and to assess patients with urticarial lesions in order to exclude or confirm other cutaneous diseases.

Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels

BACKGROUND Systemic mastocytosis is a clonal mast cell (MC) disease that can lead to potentially fatal anaphylactic reactions caused by excessive MC mediator release. The prevalence of mastocytosis in patients with Hymenoptera venom allergy is high, and thus the disease should be suspected in patients with severe reactions caused by Hymenoptera stings and increased serum basal tryptase (SBT) levels. OBJECTIVE We sought to evaluate the presence of clonal MC disorders in patients seen at our mastocytosis center with Hymenoptera sting-induced anaphylaxis, documented hypotension, absence of urticaria pigmentosa, and normal SBT levels. METHODS Twenty-two patients with Hymenoptera sting-induced anaphylaxis, without skin lesions, and with tryptase levels of less than 11.4 ng/mL underwent bone marrow evaluation. Bone mineral density was assessed in those patients with ascertained mastocytosis. RESULTS In 16 of 22 patients, a diagnosis of indolent mastocytosis could be established, and 1 patient had a monoclonal MC activation syndrome. Patients with mastocytosis had higher SBT levels (P = .03) but only rarely had angioedema/urticaria associated with hypotension (P = .004). CONCLUSIONS The absence of urticaria or angioedema in severe reactions to Hymenoptera stings with hypotension might represent the most relevant factor in identifying patients with mastocytosis, regardless of their serum tryptase levels.

Isolated bone marrow mastocytosis: an underestimated subvariant of indolent systemic mastocytosis

Systemic mastocytosis (SM) is a heterogeneous disorder characterized by the proliferation and accumulation of atypical mast cells (MC) in tissues, principally in the bone marrow (BM) and skin. The diagnosis of systemic mastocytosis requires the presence of multifocal dense mast cell infiltrates in