Investigation of underlying primary immunodeficiencies in patients with severe atopic dermatitis

BACKGROUND: Primary immunodeficiency diseases (PIDs) are a group of heterogeneous inherited disorders, characterised by recurrent infections, autoimmunity and malignancy. Some PIDs such as hyper IgE syndrome (HIES) and Wiskott-Aldrich syndrome (WAS) may be initially presented as atopic dermatitis (AD), especially in its severe form, resulting in diagnostic delay and poor prognosis of patients. OBJECTIVE: The aim of this study was to evaluate the frequency of PIDs among patients with severe AD and to determine factors that can help to raise suspicion towards these disorders. METHODS: Seventy-five patients with a well-established diagnosis of severe AD were enrolled in this study. Initial immunological evaluations, including humoral and cellular investigation, were performed in all individuals. Patients underwent further investigations in a case of suspicion of a probable PID. RESULTS: Among all patients with severe AD, five (6.6%) were diagnosed with HIES and one (1.3%) with WAS. Family history of PIDs, family history of death in early infancy, positive history of recurrent infections such as skin and respiratory infections, otitis media and sinusitis were observed significantly higher in patients with a diagnosis of PID. CONCLUSIONS: The presence of an underlying PID could explain the poor prognosis and refraction to the treatment of some patients with severe AD. Several clinical and laboratory findings can help the physicians to focus towards PIDs which are more serious. Delay in diagnosis of PID cases with skin manifestation of AD without proper management may result in lower quality of life and higher morbidity and mortality rates

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Investigation of underlying primary immunodeficiencies in patients with severe atopic dermatitis.

BACKGROUND: Primary immunodeficiency diseases (PIDs) are a group of heterogeneous inherited disorders, characterised by recurrent infections, autoimmunity and malignancy. Some PIDs such as hyper IgE syndrome (HIES) and Wiskott-Aldrich syndrome (WAS) may be initially presented as atopic dermatitis (AD), especially in its severe form, resulting in diagnostic delay and poor prognosis of patients. OBJECTIVE: The aim of this study was to evaluate the frequency of PIDs among patients with severe AD and to determine factors that can help to raise suspicion towards these disorders. METHODS: Seventy-five patients with a well-established diagnosis of severe AD were enrolled in this study. Initial immunological evaluations, including humoral and cellular investigation, were performed in all individuals. Patients underwent further investigations in a case of suspicion of a probable PID. RESULTS: Among all patients with severe AD, five (6.6%) were diagnosed with HIES and one (1.3%) with WAS. Family history of PIDs, family history of death in early infancy, positive history of recurrent infections such as skin and respiratory infections, otitis media and sinusitis were observed significantly higher in patients with a diagnosis of PID. CONCLUSIONS: The presence of an underlying PID could explain the poor prognosis and refraction to the treatment of some patients with severe AD. Several clinical and laboratory findings can help the physicians to focus towards PIDs which are more serious. Delay in diagnosis of PID cases with skin manifestation of AD without proper management may result in lower quality of life and higher morbidity and mortality rates.

The influence of systemic therapy on the serum levels of IL-6 and IL-8 in pemphigus vulgaris.

BACKGROUND: The place of cell-mediated immunity and cytokines in the immunopathogenesis of pemphigus vulgaris (PV) has not been fully established. OBJECTIVE: To assess the serum levels of pro-inflammatory cytokines, Interleukine-6 (IL-6) and Interleukine-8 (IL-8), in PV patients before and after therapy, to evaluate the influence of therapy on the serum cytokine levels. METHODS: Sixty-six newly diagnosed PV patients enrolled into the study. The serum levels of IL-8 and IL-6 were measured in 66 and 64 patients, respectively. According to the extent of skin and mucosal involvement, the patients were divided into two groups namely mild and severe. The serum levels of cytokines were measured using enzyme-linked immunosorbent assay (ELISA) method before and after 4 weeks of prednisolone plus azathioprine therapy. RESULTS: In 64 patients studied for the serum level of IL-6, the median IL-6 level was significantly decreased from 1.6 to 0.9 pg/mL by therapy (P-value = 0.001). Segregating the patients according to the severity of the disease, the serum level of IL-6 did not differ significantly by therapy in patients with a mild disease. However, in patients with a severe disease the median serum level of IL-6 decreased significantly from 1.8 to 0.9 pg/mL after therapy (P-value = 0.001). No significant changes were found in the IL-8 level by treatment. CONCLUSION: The significant decrease in the IL-6 level after therapy suggests that blocking of IL-6 could have therapeutic benefits for the treatment of PV, particularly in severe forms.

Randomized double blind trial of prednisolone and azathioprine, vs. prednisolone and placebo, in the treatment of pemphigus vulgaris.

BACKGROUND: The classic treatment for pemphigus vulgaris is prednisolone. Immunosuppressive drugs can be used in association. OBJECTIVE: To compare the efficacy of Azathioprine in reducing the Disease Activity Index (DAI). PATIENTS AND METHODS: A double blind randomized controlled study was conducted on 56 new patients, assigned to two therapeutic groups: (i) prednisolone plus placebo; (ii) prednisolone plus Azathioprine. Patients were checked regularly for 1 year. 'Complete remission' was defined as healing of all lesions after 12 months, and prednisolone <7.5 mg daily, (DAI ≤ 1). Analysis was done by 'Intention To Treat' (ITT) and 'Treatment Completed Analysis' (TCA). RESULTS: Both groups were similar in age, gender, disease duration, and DAI. Primary endpoint: By ITT and TCA, the mean DAI improved in both groups with no significant difference between them. The difference became significant for the last trimester (3 months; ITT: P = 0.033, TCA: P = 0.045). Secondary endpoint: The total steroid dose decreased significantly in both groups, with no significant difference between them, except for the last trimester (ITT: P = 0.011, TCA: P = 0.035). The mean daily steroid dose decreased gradually in both groups becoming statistically significant in favour of azathioprine, in the last trimester, especially at 12th months (ITT: P = 0.002, TCA: P = 0.005). Complete remission was significant at 12 months only for TCA (AZA/Control: 53.6%/39.9%, P = 0.043). LIMITATIONS: Sample size was rather small to demonstrate all differences. Other limitations include the choice of primary and secondary endpoints and the unavailability to measure thiopurine methyltransferase activity. CONCLUSION: Azathioprine helps to reduce prednisolone dose in long-run.

Serum and salivary desmoglein 1 and 3 enzyme-linked immunosorbent assay in pemphigus vulgaris: correlation with phenotype and severity.

BACKGROUND: To the best of our knowledge there is only one report about salivary desmoglein (Dsg) 1 and 3 enzyme-linked immunosorbent assay (ELISA) in pemphigus vulgaris (PV), whereas several studies have been performed on serum. AIMS: To find the sensitivity of serum and salivary anti-Dsg1 and 3 antibodies in the diagnosis of PV, and to determine the relationship between disease severity and phenotype with antibody levels. METHODS: Fifty new patients with PV were included in this study. The diagnosis of PV was confirmed by histopathology and direct immunofluorescence. Demographical data, disease severity and phenotypes were recorded on questionnaire sheets. Dsg1 and Dsg3 ELISA were performed on serum and salivary samples of patients and controls. RESULTS: Thirty-seven patients had mucocutaneous phenotype; whereas mucosal dominant and cutaneous dominant phenotypes were seen in 11 and 2 patients respectively. The sensitivities of serum anti-Dsg3 and anti-Dsg1 were 94% and 72% respectively. The sensitivities of salivary anti-Dsg3 and anti-Dsg1 antibodies were accordingly 94% and 70%. Compared with mucosal phenotype, serum and salivary anti-Dsg1 antibodies were significantly higher in the patients with mucocutaneous phenotype. Serum Dsg1 antibodies were related with cutaneous and serum Dsg3 antibodies with mucosal severity scores. Salivary Dsg1 antibodies were significantly correlated with mucosal severity (P=0.00); however there was no correlation between this antibody and cutaneous severity (P=0.07). Salivary Dsg3 antibodies were not correlated with mucosal severity (P=0.16). CONCLUSION: Saliva Dsg ELISA could be used for diagnosis of PV. Salivary Dsg1 antibodies had a significant correlation with mucosal severity.

Narrow-band UVB in the treatment of early stage mycosis fungoides: report of 16 patients.

Although early stage mycosis fungoides (MF) has a generally good prognosis, and long-term survival rates with current therapies (UVB, photochemotherapy, topical nitrogen mustard, electron beam radiotherapy) are similar, there is concern regarding their potential side effects. It has been reported that the same effective UVB dose is safer than PUVA in terms of carcinogenicity, and that it produces fewer side effects. Our aim was to evaluate the effect of narrow-band UVB in the treatment of early stage MF. Sixteen patients (seven males, nine females; mean age, 40 years) with early stage MF received TL-01 phototherapy three times per week using a standard protocol. Twelve patients (75%) had complete response in a mean of 27.9 treatments, three had partial response, and one no response. Upon discontinuation of treatment, six patients with complete response relapsed in a mean time to relapse of 4.5 months. The present study indicates that narrow-band-UVB is an effective treatment modality for early stage MF.

[Open trial of mycophenolate mofetil in the treatment of resistant pemphigus vulgaris]. / Etude ouverte du mycophénolate mofetil dans le traitement du pemphigus résistant.

BACKGROUND: Pemphigus vulgaris is a severe autoimmune blistering disease of the skin and mucous membranes. In absence of treatment, mortality is high. In the past, prednisolone was the best treatment. Later, combination therapy with systemic prednisolone and other disease-modifying drugs was tried with better results. Unfortunately, some patients do not respond well to such treatment, or may exhibit multiple recurrences or complications. Some other patients may remain on high dose corticosteroids to maintain remission. OBJECTIVE: To evaluate the efficacy and safety of mycophenolate mofetil as a steroid sparing agent in the treatment of resistant pemphigus vulgaris. METHODS: We administered 2 g daily mycophenolate mofetil with systemic steroids to 10 patients with resistant and severe disease who did not respond to conventional therapy, or had multiple recurrences. RESULTS: Nine of the ten patients responded to treatment and showed complete clearance of lesions within 6 to 16 weeks of therapy. At the end of six months, the dose of prednisolone was significantly lower. Side effects were few and mild. After discontinuation of mycophenolate mofetil, 5 of the 9 patients relapsed. CONCLUSION: Mycophenolate mofetil is effective and safe as a disease-modifying drug combined with prednisolone in the treatment of patients with resistant pemphigus vulgaris. To induce long lasting remission has to be administrated for more than 6 months.