Idiopathic guttate hypomelanosis: an electron microscopy study.

BACKGROUND: Few published data, concerning the electron microscopy findings of idiopathic guttate hypomelanosis have been published so far. OBJECTIVES: To reveal the electron microscopic findings of idiopathic guttate hypomelanosis and their aetiopathogenetic associations. METHODS: Punch biopsy specimens from four patients with idiopathic guttate hypomelanosis, after being properly processed, were observed under the electron microscope. RESULTS: In the epidermis, melanocytes and melanosomes were normal in structure. In some areas, there was a reduced uptake of melanosomes by the keratinocytes. In the dermis, fibroblasts were structurally normal. Also, most elastic and collagen fibres were normal, but there were focal elastotic changes. CONCLUSIONS: No significant structural abnormality of the melanocytes was observed, but rather a functional defect in the transfer of melanosomes from the melanocytes to the keratinocytes.

Pilot study of 19 patients with severe pemphigus: prophylactic treatment with rituximab does not appear to be beneficial.

AIMS: To assess the efficacy and safety of rituximab in refractory pemphigus and the possible benefit of an additional prophylactic infusion at 6 months. METHODS: Seventeen patients with pemphigus vulgaris, 1 with pemphigus foliaceus and 1 with pemphigus vegetans were treated with 4 weekly infusions of rituximab (375 mg/m(2)). Nine patients received an additional prophylactic infusion after 6 months while the rest received no maintenance therapy. In case of recurrence, an additional single infusion was administered. RESULTS: Control of the disease was obtained after 3-8 weeks. End of the consolidation phase for all patients was observed after 16 weeks. Patients remained in full remission for 7-42 months. All immunosuppressive agents, including prednisone, were discontinued after 2-12 months. The disease relapsed in 5 out of 9 patients who received the additional prophylactic infusion, and in 3 out of 10 patients among those skipping the prophylactic additional infusion. CONCLUSION: One course of rituximab and treatment of relapses is highly effective and well tolerated in the treatment of refractory pemphigus. In this pilot study of 19 patients, the prophylactic infusion does not appear to have provided any additional benefit to the patients receiving it.

Sleep apnea as a comorbidity in obese psoriasis patients: a cross-sectional study. Do psoriasis characteristics and metabolic parameters play a role?

BACKGROUND: Psoriasis is associated with a variety of comorbidities such as obesity and cardiovascular disease. OBJECTIVE: In a cross-sectional study, we explored whether obstructive sleep apnea and hypopnea syndrome (OSAHS) is associated with psoriasis characteristics and metabolic parameters. METHODS: Thirty-five patients with chronic plaque psoriasis underwent a nocturnal polysomnography study and were analysed for Apnoea-Hypopnoea Index to assess OSAHS severity and Framigham score to predict the absolute risk of coronary artery disease at 10 years. The association of OSAHS with psoriasis was examined according to psoriasis characteristics (PASI and DLQI scores, disease duration and previous use of systemic treatments), metabolic parameters (Body Mass Index - BMI, waist to hip ratio - WHR, lipid profile) and other comorbidities (obesity, hypertension, arthritis and cardiovascular disease). RESULTS: There was no correlation between psoriasis characteristics and OSAHS. Psoriasis patients with OSAHS presented more frequent snoring and lower sleep quality compared with those without OSAHS. In univariate analyses, OSAHS was associated with increased BMI and hypertension in psoriasis patients. In multivariable logistic regression models, there was statistically significant evidence that only BMI and hypertension were associated with increased risk of OSAHS, adjusting for psoriasis characteristics, age and gender. Presence of metabolic syndrome, WHR, and smoking were not significant risk factors for OSAHS. In subgroup analyses, OSAHS correlated with duration of psoriasis (>8 years) in women (P = 0.021) and with Framigham score in men (P = 0.035). CONCLUSION: OSAHS may be a comorbidity in obese psoriasis patients with hypertension. Treatment with continuous positive airway pressure and weight loss interventions should be initiated.

Prevalence of non classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Greek women with acne: a hospital-based cross-sectional study.

AIM: To determine the prevalence and frequency of non classical congenital adrenal hyperplasia (NC-CAH) due to 21-OHD at the time of clinical presentation and at the peripubertal period in a substantial sample of Greek women with acne and to investigate the correlation of serum T, 17-OHP and DHEA-S with acne appearance at the time of clinical presentation. METHODS: One hundred and twenty-three unselected women with hyperandrogenemic symptoms were examined. After the ACTH stimulation test, 6 (4.9%) women were diagnosed with NC-CAH due to 21-OHD. RESULTS: There was not any statistical significant difference in the frequency of peripubertal acne between NC-CAH group of patients (6.4%) and patients with hyperandrogenemia of other aetiology (93%), mainly ovarian (P = 0.41). However, there was a statistical significant difference in the prevalence of acne at the time of clinical examination between the two groups (P = 0.04). Acne was present in 83.3% of women with NC-CAH vs. 41.02% of women in the hyperandrogenic group without NC-CAH. A statistically significant decrease of acne from the peripubertal time to the time of clinical examination in the group of women with hyperandrogenemia of other aetiology (-21.37%) was observed compared to women with NC-CAH (P < 0.001). CONCLUSION: We have shown that acne persists from peripubertal period to adult life in NC-CAH women whereas it tends to diminish in women with hyperandrogenemia of other aetiology. Acne is a prominent finding in women with NC-CAH. Serum concentrations of 17-OHP after ACTH stimulation (17-OHP6O ) should be investigated in women with persistent acne in adult life.

Serum neurotensin (NT) is increased in psoriasis and NT induces vascular endothelial growth factor release from human mast cells.

BACKGROUND: Psoriasis involves skin inflammation that often worsens with stress, but the mechanism of this effect remains obscure. We have shown that corticotropin-releasing hormone (CRH) is increased in the serum of patients with psoriasis. A peptide, neurotensin (NT), can trigger skin histamine release and augment the ability of CRH to increase skin vascular permeability. OBJECTIVES: To investigate the serum level of NT, and the expression of genes for NT and NT receptor-1 (NTR-1) in lesional and nonlesional skin of patients with psoriasis, compared with normal controls. Also, to study the effect of NT on human mast cell release of vascular endothelial growth factor (VEGF), which is increased in psoriatic skin. METHODS: Serum was obtained from patients with psoriasis (n = 56) and controls (n = 33); NT levels were measured with the Milliplex microbead assay. Biopsies were obtained from the lesional and nonlesional skin of patients with chronic plaque psoriasis (n = 40), who had not received any treatment for at least 15 days and were free of any systemic inflammatory diseases. Control skin samples were obtained from healthy subjects (n = 30). Expression of genes for NT and NTR-1 in the skin was evaluated by quantitative reverse transcriptase-polymerase chain reaction. LAD2 human mast cells were stimulated by NT (1 µmol L(-1)) for 24 h and VEGF was measured by enzyme-linked immunosorbent assay. RESULTS: Serum NT was increased in patients with psoriasis, while expression of genes for NT and NTR-1 in lesional skin was decreased compared with controls. NT induced VEGF release from mast cells and was augmented by interleukin-33. CONCLUSION: NT may play a role in psoriasis pathogenesis and its worsening by stress, at least in part through activation of skin mast cells.

Single nucleotide polymorphisms of toll-like receptor-4 protect against acne conglobata.

BACKGROUND: Former studies have shown that Propionibacterium acnes may stimulate expression of toll-like receptor 4 (TLR4) in keratinocytes of patients with acne vulgaris. OBJECTIVE: To investigate the impact of single nucleotide polumorphisms (SNPs) of the TLR4 gene in acne vulgaris. METHODS: Genomic DNA was isolated from 191 patients with acne vulgaris and 75 healthy controls. Asp299Gly and Thr399Ile SNPs were defined after cutting of the PCR products by restriction enzymes. Sebum of lesions was cultured for P. acnes. RESULTS: No differences in SNP allele frequencies were found between patients and healthy controls. 46.5% of carriers of wild-type alleles were suffering from acne conglobata compared with 28.6% of carriers of SNP alleles (P=0.040). After adjusting for gender, family history of acnes, intake of any therapy and skin isolation of P. acnes, carriage of TLR4 gene SNPs was the only independent variable linked with a protective role against acne conglobata (OR=0.269, P=0.014). No differences were found in the amount of pro-inflammatory cytokines released by peripheral blood mononuclear cells isolated from patients with acne conglobata carrying only wild-type alleles and SNP alleles. CONCLUSIONS: Carriage of gene SNPs is protective against the development of acne conglobata even in the presence of P. acnes.

The role of inflammatory markers in assessing disease severity and response to treatment in patients with psoriasis treated with etanercept.

BACKGROUND: Psoriasis is a chronic, systemic, inflammatory disease. Inflammatory markers are used in clinical practice to detect acute inflammation, and as markers of treatment response. Etanercept blocks tumour necrosis factor (TNF)-α, which plays a central role in the psoriatic inflammation process. AIM: To reveal any possible association between disease severity [measured by Psoriasis Area and Severity Index (PASI)] and the inflammatory burden (measured by a group of inflammatory markers), before and after etanercept treatment. METHODS: In total, 41 patients with psoriasis vulgaris, eligible for biological treatment with etanercept, were enrolled in the study. A set of inflammatory markers was measured, including levels of white blood cells and neutrophils, fibrinogen, ferritin, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), haptoglobin, ceruloplasmin and α1-antitrypsin, before and after 12 weeks of etanercept 50 mg twice weekly. RESULTS: All markers were reduced after treatment (P < 0.001). PASI correlated with fibrinogen and hs-CRP. Of the 41 patients, 19 (46.3%) achieved reduction of 75% in PASI (PASI75). An increase in hs-CRP and ESR difference (values before minus values after treatment) was related to higher likelihood of achieving PASI75. CONCLUSIONS: Inflammatory markers, particularly hs-CRP and to a lesser extent, fibrinogen and ESR, can be used to assist in assessing disease severity and response to treatment in patients with psoriasis. A combination of selected inflammatory factors (which we term the Index of Psoriasis Inflammation) in combination with PASI might reflect inflammatory status in psoriasis more accurately than each one separately.

Development of two primary malignant melanomas after treatment with adalimumab: a case report and review of the possible link between biological therapy with TNF-alpha antagonists and melanocytic proliferation.

Biologics, such as tumor necrosis factor alpha (TNF-alpha) antagonists, have revolutionized treatment of several significant inflammatory autoimmune diseases. Nevertheless, issues concerning long-term safety remain to be clarified. There is growing evidence linking biological treatments with the occurrence of malignancies or reactivation of latent ones, including malignant melanoma. We report the case of a 75-year-old male patient who developed 2 primary malignant melanomas (MM) after treatment with adalimumab for rheumatoid arthritis. He was under adalimumab treatment for approximately 12 months before the diagnosis of MM on his right lower leg. After surgical removal and staging, no evidence of metastases was found. A few months later, a second MM developed on the patient's scalp. The short duration of treatment with adalimumab and the unclear temporal relationship cannot adequately support a probable link between this double MM occurrence and the adalimumab-induced immunosuppressive state. The result of a literature search regarding the possible association between anti-TNF drugs and melanocytic proliferation is provided.

Erythema multiforme following vaccination for human papillomavirus.

Erythema multiforme (EM) is an acute self-limited immune-mediated reaction manifested by target skin lesions with mucous membrane involvement. The most common causes are infections and drugs. Vaccinations have been reported as a triggering factor, and they may be a frequent cause of EM in childhood. A 19-year-old female developed several target lesions of the hands and feet 10 days after the second dose of human papillomavirus (HPV) vaccine. Clinico-histologically, a diagnosis of EM minor was made. Treatment with topical corticosteroids and oral antihistamines resulted in complete clearance of the rash. Four months later, she received the last booster dose of the vaccine. A few subtle lesions appeared and disappeared spontaneously after a few days. Gardasil is a non-infectious vaccine, developed for the prevention of cervical cancer, precancerous genital lesions and genital warts. It delivers the major capsid (L1) protein of HPV types 6, 11, 16 and 18. Mild local reactions are the main adverse events. The only serious events are very rare cases of anaphylaxis. In our patient, the temporal relationship between the development of EM and the vaccination suggests that the HPV vaccine probably was the causal agent. This is the first published case of EM following HPV vaccination.

A randomized, double-blind, vehicle-controlled study of a preparation containing undecylenoyl phenylalanine 2% in the treatment of solar lentigines.

BACKGROUND: Solar lentigines are common, benign, cosmetically disfiguring lesions. Available physical treatments are effective, but they are costly and carry risks of side-effects. OBJECTIVE: To evaluate the efficacy and safety of a preparation containing undecylenoyl phenylalanine 2% in the topical treatment of solar lentigines. METHODS: In total, 36 patients with solar lentigines of the hands were randomly assigned to apply the active preparation on one side and the vehicle alone on the other side, twice daily for 12 weeks. Patients were evaluated monthly for efficacy and safety. RESULTS: In all, 30 patients (28 women and 2 men; age range 47-75 years) completed the study. The duration of lesions ranged from 8 months to > 10 years. All patients responded partially on the side of the active treatment. Of the partial responders, 19 (63.3%) had moderate improvement and 11 (36.6%) had marked improvement. Improvement was evident from the first follow-up visit. On the side of the vehicle, 26 remained stable (86.6%) and 4 (13.3%) had partial improvement. There was a significant difference (P < 0.01) in efficacy of the active preparation vs. the vehicle. Using patient assessment ratings, 80% were 'much more satisfied/more satisfied' with the result. The reported side-effects were minor and included erythema and itching or burning on the side of active treatment. CONCLUSIONS: Undecylenoyl phenylalanine 2% is a novel depigmenting agent, which possibly acts as an alpha-melanocyte-stimulating hormone antagonist, thus inhibiting melaninogenesis. It achieved a significant lightening of the lesions with minimal side-effects. Most patients were satisfied with the improvement. Undecylenoyl phenylalanine 2% may represent a safe, effective and inexpensive therapeutic alternative for solar lentigines.

Stasis dermatitis-like leukaemic infiltration in a patient with myelodysplastic syndrome.

We report a case of leukaemia cutis presenting as stasis dermatitis-like eruption in a patient with myelodysplastic syndrome progressing to acute myelogenic leukaemia.