Anna Woźniacka

Vitamin D effects in atopic dermatitis

BACKGROUND Because vitamin D has immunomodulatory properties and immunologic mechanisms play a role in the pathogenesis of atopic dermatitis (AD), it is possible that vitamin D may influence the activity of AD. OBJECTIVE The aim of the study was to correlate vitamin D concentrations in patients who had AD with clinical, immunologic, constitutional, and environmental factors, and to determine if vitamin D supplementation affects the clinical manifestations of AD. METHODS Clinical and laboratory parameters of 95 patients with AD and 58 control subjects were measured. Severity of AD was assessed with the SCORAD index. RESULTS The mean serum concentration of 25(OH)D3 in patients with AD was not statistically different from control subjects. The frequency of bacterial skin infections was higher in patients with AD who had lower 25(OH)D₃ levels. No statistical associations between vitamin D levels and other multiple laboratory and clinical parameters were found. After supplementation both mean objective SCORAD and SCORAD index were significantly lower (P < .05). LIMITATIONS All study patients were Caucasians and only one supplemental vitamin D dose and treatment duration were assessed. CONCLUSION The results from this study indicate that vitamin D supplementation may help ameliorate clinical signs of the disease and can be considered as a safe and well-tolerated form of therapy.

Clinical significance of circulating dendritic cells in patients with systemic lupus erythematosus

Dendritic cells are a complex group of mainly bone-marrow-derived leukocytes that play a role in autoimmune diseases. The total number of circulating dendritic cells (tDC), and their plasmacytoid dendritic cell (pDC) and myeloid dendritic cell (mDC1 and mDC2) subpopulations were assessed using flow cytometry. The number of tDC and their subsets were significantly lower in systemic lupus erythematosus patients than in the control group. The count of tDC and their subsets correlated with the number of T cells. The number of tDC and pDC subpopulation were lower in the patients with lymphopenia and leukopenia than in the patients without these symptoms. Our data suggest that fluctuations in blood dendritic cell count in systemic lupus erythematosus patients are much more significant in pDC than in mDC, what may be caused by their migration to the sites of inflammation including skin lesions. Positive correlation between dendritic cell number and TCD4+, TCD8+ and CD19+ B cells, testify of their interactions and influence on SLE pathogenesis. The association between dendritic cell number and clinical features seems to be less clear.

Multiple myeloma in a patient with systemic lupus erythematosus, myasthenia gravis and non-familial diffuse palmoplantar keratoderma.

The coexistence of autoimmune diseases and malignancies including lymphoproliferative diseases is often reported in the literature. Here we report an unusual case with two autoimmune diseases--myasthenia gravis (MG) and systemic lupus erythematosus (SLE) associated with unique palmoplantar keratoderma (PK) which preceded the development of multiple myeloma (MM) for twenty and seven years respectively. MG associated with non-malignant thymoma developed in 1981 and was successfully treated with thymectomy and physostigmine. Thirteen years later SLE was diagnosed and until now it is also accompanied by skin lesions corresponding to non-familial, diffuse palmoplantar keratoderma which is resistant to treatment. In 2001 the patient revealed inguinal and abdominal lymphadenopathy first diagnosed as extramedullary plasmacytoma and then as multiple myeloma on the basis of bone marrow infiltration and monoclonal gammopathy. Therapy with VAD regimen achieved complete remission of the MM and significant improvement of the skin changes lasting for six months. We failed to collect sufficient numbers of CD 34+ cells for peripheral blood stem cell transplantation. Now the malignancy is in partial remission after CHOP therapy and the skin lesions have returned to their initial status. To our knowledge, this is the first case to be reported with coexistence of these four diseases.

Intractable headaches, ischemic stroke, and seizures are linked to the presence of anti-β2GPI antibodies in patients with systemic lupus erythematosus.

Background Neuropsychiatric systemic lupus erythematosus (NPSLE) is a common and potentially fatal manifestation of SLE. Antiphospholipid antibodies (aPL) such as lupus anticoagulant (LA), anticardiolipin (aCL) and antibodies to β2glycoprotein I (anti-β2GPI), the most important aPL antigen, are thought to play a role in some forms of NPSLE. As of yet, their specific roles in NPSLE manifestations remain to be elucidated. Methodology/Principal Findings 57 SLE patients (53 women) were assessed for LA, aCL and anti-β2GPI twice, to determine persistent positivity. All patients were examined by neurology and psychiatry specialists. 69 healthy subjects were assessed as controls. NPSLE was diagnosed in 74% of patients. Headaches were the most prevalent manifestation of NPSLE (39%), followed by cerebrovascular disease (CVD) (23%), depressive disorders (19.0%), and seizures (14%). NPSLE and non-NPSLE patients showed comparable SLE activity and corticosteroid use. In 65% of patients neuropsychiatric manifestations preceded SLE diagnosis. aPL profiles of NPSLE patients and non-NPSLE patients were similar. Headaches and ischemic stroke were independently associated with anti-β2GPI-IgM (OR=5.6; p<0.05), and seizures were linked to anti-β2GPI-IgG (OR=11.3; p=0.01). Conclusions In SLE patients, neuropsychiatric manifestations occur frequently and early, often before the disease is diagnosed. Autoantibodies to β2GPI are linked to non-specific headaches, ischemic stroke and seizures, and show a better predictive value than aCL and LA. These findings may help to improve the diagnosis of NPSLE and should prompt further studies to characterize the role of anti-β2GPI in the pathogenesis of this condition.

Vitamin D Receptor Gene BsmI Polymorphism in Polish Patients with Systemic Lupus Erythematosus

The hormonally active form of vitamin D3, 1,25(OH)2D3 (calcitriol), exerts actions through VDR receptor, which acts as a transcriptional factor. Calcitriol is an immunomodulator that affects various immune cells, and several studies link it to many autoimmune diseases. BsmI polymorphism affects the level of VDR gene transcription, transcript stability, and posttranscriptional modifications. It seems to be related to the systemic lupus erythematosus (SLE). Our study examined the characteristics of VDR gene BsmI polymorphism in Polish SLE patients and their relationship with clinical manifestations of the disease. We genotyped 62 patients with SLE and 100 healthy controls using the real-time PCR. There were no differences observed in the frequency of BsmI genotypes in SLE patients and in the control group. There was no significant correlation between BsmI genotypes and clinical symptoms of SLE, but the AA genotype correlates with higher levels of antinuclear antibodies (ANA) in this group (r = 0.438; P = 0.002). A larger study examining BsmI and other VDR gene polymorphisms is needed. It may allow explaining differences in the clinical picture of the disease and choosing a personalized therapy.

Exacerbations of bipolar disorder triggered by chloroquine in systemic lupus erythematosus—a case report

Despite precise definitions and exclusions for 19 syndromes of neuropsychiatric systemic lupus erythematosus (NPSLE), under some circumstances it appears to be difficult to differentiate whether neuropsychiatric symptoms are caused by SLE or by other reasons such as primary mental disorders or substance-induced mood disorders, especially induced by glucocorticoids or antimalarials. We report the case of a male patient with SLE who presented with an exacerbation of bipolar disorder triggered by chloroquine. Firstly, when the patient was diagnosed with SLE, he underwent six months of therapy with chloroquine without any psychiatric symptoms. Later, the SLE returned and the patient was prescribed chloroquine again, without any mental illness. When the third exacerbation of SLE occurred, it coincided with a severe depressive episode with psychotic features that became aggravated for the first time after the administration of chloroquine. The chloroquine was subsequently replaced with hydroxychloroquine for the next six months without any behavioral problems, following which, the SLE and mood disorder were in remission. Later, a bipolar disorder relapse occurred, manifested by a manic episode, and in the following three months, despite psychiatric treatment, a manic episode with psychotic features developed four days after chloroquine was prescribed for arthritis. It was the second time that the mood disorder was exacerbated by chloroquine. Since that time, chloroquine has been withdrawn. Currently the patient is undergoing treatment with hydroxychloroquine and psychiatric drugs with good response. Our case points out that although chloroquine-induced psychosis is rare, patients presenting with behavioral changes need physicians’ attention in order to diagnose early and efficiently treat encountered mood disorders.

Plaque form of warty dyskeratoma – acantholytic dyskeratotic acanthoma

We report the case of a 64‐year‐old man with a plaque‐like lesion on the lower back. Clinically, squamous cell carcinoma was suspected, but the histological features resembled those of isolated Darier’s disease or pemphigus vegetans. The lesion was removed with the final diagnosis of acantholytic dyskeratotic acanthoma. We discuss this case with special regard to the differential diagnosis of other isolated acantholytic acanthomas.

Tumour necrosis factor α (TNF-α), interleukin-6 (IL-6) and their soluble receptors (sTNF-α-Rp55 and slL-6R) serum levels in systemic lupus erythematodes

We investigated a possible association between serum concentrations of tumour necrosis factor α (TNF-α), interleukin-6 (IL-6) and their soluble receptors (sTNF-α-Rp55 and sIL-6R) using an enzyme-linked immunosorbent assay (ELISA) in 55 patients with systemic lupus erythematodes (SLE) and 16 healthy controls. We also examined a possible association between the serum levels of these peptides and SLE activity, as well as TNF-α and IL-6 concentrations and the levels of their soluble receptors. The median concentrations of TNF-α, sTNF-α-Rp55 and IL-6 were significantly higher in SLE patients than in normal individuals. In contrast, there was no difference between the serum level of sIL-6R in both groups. We found positive correlations between the serum concentrations of TNF-α and IL-6 as well as their soluble receptors and disease activity. There were also correlations between TNF-α and sTNF-α-Rp55 as well as IL-6 and sIL-6R serum levels in SLE patients but there were no such correlations in the normal control group. In conclusion, an increase in the serum levels of TNF-α, sTNF-α-Rp55 and IL-6 may become useful markers for SLE activity. Patients with SLE have sIL-6R serum concentration similar to that as in normal individuals. However, it correlates with disease activity and the level of IL-6.

Correlation between IL-36α and IL-17 and Activity of the Disease in Selected Autoimmune Blistering Diseases

Dermatitis herpetiformis (DH), bullous pemphigoid (BP), and pemphigus vulgaris (PV) are autoimmune bullous skin conditions with eosinophilic and neutrophilic infiltrations. While cytokines are crucial for the affinity and activation of different leukocyte cells in the inflammation and blister formation, there are no studies concerning a role of IL-36. The goal of the study was to analyze whether interleukin 36 is involved in pathogenesis of DH, BP, and PV. And the second aim of the study was the estimation of correlation between Il-36 and IL-17 and titers of specific antibodies in these diseases. Expression of IL-36 and IL-17 was detected in serum in all DH, BP, and PV samples. Serum levels of IL-36 and IL-17α were statistically higher in DH, BP, and PV groups as compared to the control group. IL-36α levels were statistically higher in DH patients, as compared to patients with PV and BP. Our results showed that IL-36 may be helpful in the diagnostic and monitoring of the activity of the disease. IL 36 may play a relevant role of enrolling eosinophils and neutrophils in DH, BP, and PV and finally provoke tissue injury.

Antinuclear antibodies in rosacea patients.

Introduction Rosacea is a common inflammatory disorder, characterized by a spectrum of facial manifestations. The clinical similarity to other dermatoses, like lupus erythematosus, might lead to misdiagnosis, particularly in patients with elevated antinuclear antibody titers. Aim To assess the frequency, titer and specificity of antinuclear antibodies in rosacea patients and correlate these findings with clinical features. Material and methods The study included 101 rosacea patients and 26 sex- and age-matched controls. Immunofluorescence antinuclear antibody testing was performed on HEp-2 substrates. Patients’ sera with ANA titers of 1 : 160 or higher were evaluated by Euroline analysis. Results Over a half (53.5%) of rosacea patients had an ANA titer greater than or equal to 1 : 160. Within this group 13.86% had a titer of 1 : 320, 8.91% had a titer of 1 : 640, and 6.93% had a titer of 1 : 1,280 or higher. The specificity of these antibodies could not be identified. Elevated ANA titers were present more often in women (55.8%) than in men (44.15%). Only two of 26 healthy volunteers had elevated ANA titers. One had a titer of 1 : 160 and the other of 1 : 320. During a two-year observation period, after the initial ANA testing, none of the patients with ANA titers above 1 : 640 developed an apparent autoimmune disorder. Conclusions Elevated ANA titers are commonly found in rosacea patients, what with simultaneously existing facial erythema and photosensitivity might lead to misdiagnosis of lupus erythematosus. Clinicians should beware of these findings to avoid misdiagnosing lupus erythematosus in rosacea patients with elevated ANA titers.