Jerzy Jarząb

Molecular mechanisms of glucocorticoids action: implications for treatment of rhinosinusitis and nasal polyposis

Intra-nasal glucocorticoids are the most effective drugs available for rhinosinusitis and nasal polyposis treatment. Their effectiveness depends on many factors and not all of them have been well recognized so far. The authors present the basic information on molecular mechanisms of glucocorticoid action, direct and indirect effects of glucocorticoids on transcription of genes encoding inflammatory mediators. They focus on recently proved nongenomic mechanisms which appear quickly, from several seconds to minutes after glucocorticoid administration and discuss clinical implications resulting from this knowledge. Discovery of nongenomic glucocorticoid actions allows for better use of these drugs in clinical practice.

Efficacy and safety of birch pollen immunotherapy for local allergic rhinitis

BACKGROUND Local allergic rhinitis (LAR) is a relatively new disease. OBJECTIVE To ascertain the effects of allergen-specific immunotherapy in LAR. METHODS A randomized, double-blind, placebo-controlled trial of birch subcutaneous allergen immunotherapy (AIT) for LAR was performed in 28 patients. The therapy was performed for 24 months in 15 patients with AIT and 13 patients given placebo. The primary end point was decrease in symptom medication score (SMS). In addition, we monitored serum-specific immunoglobulin E (IgE), serum-specific immunoglobulin G4, nasal-specific IgE to Bet v 1, and safety and quality-of-life parameters. RESULTS After 24 months of treatment, there was a significant decrease in the median area under the curve for SMS of the active group vs the placebo group: 2.14 (range, 1.22-4.51) vs 6.21 (range, 5.12-7.89), at the P < .05 level. During AIT, the active group showed a significant decrease in SMS of up to 65% vs baseline. A significant increase in immunoglobulin G4 and decrease in nasal-specific IgE were observed in the active group during AIT compared with the placebo group. AIT was well-tolerated and without systemic reactions. CONCLUSION This study demonstrates that AIT for birch pollen in patients with LAR was clinically effective and exhibited good tolerance. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03157505.

Frequency of IgE-dependent hypersensitivity to moulds in patients with chronic rhinosinusitis with polyps.

Introduction The complicated etiology of chronic sinusitis with polyps and frequent allergy to mould is established. Aim We aimed to investigate the frequency of the IgE-dependent hypersensitivity in this group of patients and prove the need of surgery in allergic chronic rhinosinusitis patients. Material and methods Forty-two patients (19 females, 23 males) aged 34–73 years (55 ±12.6 years), with chronic sinusitis with polyps were included into the study. Functional endoscopic sinus surgery, laryngological examination, sinus computed tomography scans, and smear from maxillary sinus for microbiological examination were done in all patients. Skin prick tests with common perennial and seasonal inhalant allergens, tIgE and sIgE against moulds were required. Results Thirty-two of 42 patients (71.4%) were allergic to at least one inhalant allergen. A mean concentration of total IgE was 241.2 ±186.3 kU/l (35.0–708.0 kU/l) and was lower in patients with fungal culture found in sinus mucin than in patients without fungal presence 75.1 ±54.6 kU/l vs. 284.3 ±204.1 kU/l. We found no difference in the number of positive skin prick tests in a group with and without fungal culture. None of patients with fungal culture found in sinuses presented a detectable level of mold sIgE. All patients with fungal vegetation in sinuses required at least two polypectomy procedures. Conclusions The total IgE concentration was significantly lower in patients with fungal presence in sinuses. Nasal polyps occurred more frequently in patients with fungal presence in sinuses.

The frequency of polymorphic variants of filaggrin gene and clinical atopic dermatitis

Introduction As far as pathogenesis of the atopic dermatitis (AD) is concerned, the roles of an impaired epidermal barrier and cornified cell envelope are widely emphasized. Aim The assessment of mutations of the filaggrin gene and their connection with the clinical picture of AD as well as selected allergological and environmental indicators. Material and methods 105 patients with diagnosed AD on the basis of diagnostic criteria were included. For every patient of the examined group, quantitative determination of the total concentration of IgE and the concentration of IgE antibodies to selected allergens were examined. For all patients, studies were performed by means of analysis of two genomic gene variants of profilaggrin (FLG) – R501X and 2282del4. Results Loss-of-function mutations in the filaggrin gene were shown in 12 (11.4%) patients in the examined group. All patients in the study group who developed one of the tested loss-of-function mutations in the filaggrin gene demonstrated an extrinsic, allergic form of atopic dermatitis. A significant association (p = 0.0002) between the presence of one of the tested loss-of-function mutations in the filaggrin gene and elevated levels of total concentration of immunoglobulin E was shown. Conclusions Patients with AD of null mutations in the filaggrin gene demonstrate a relationship with the total and specific concentration of immunoglobulin E, specifically higher concentrations of IgE against aeroallergens and alimentary allergens as well as elevated levels of total immunoglobulin E.

The clinical differences of asthma in patients with molds allergy

INTRODUCTION Bronchial asthma is an increasing problem worldwide. The course of bronchial asthma is dependent on the type of inducing allergens. The differences between the clinical features of asthma in patients with monovalent allergies to molds and with other allergies were explored. MATERIAL AND METHODS Randomly selected 1910 patients (924 women and 986 men) between 18-86 years in age were analyzed according to type of allergy and asthma. The diagnosis of asthma was confirmed on the basis of GINA criteria, physical examination and spirometry. Allergy diagnosis was confirmed on the basis of medical history, a positive skin prick test and the measurement of serum-specific IgE to inhalant allergens, using an extended profile of mold allergens. RESULTS Patients with monovalent allergies to molds (4% of analyzed group) had significantly more frequent diagnoses of asthma than patients in the other group (53% vs. 27.1-32.4%, p < 0.05). Patients with allergies to Alternaria alternata had an odds ratio of 2.11 (95%CI: 1.86-2.32) for receiving a diagnosis of bronchial asthma. They had less control over their asthma, which was more severe compared to patients with other allergies. Patients with asthma and allergies to mold had significantly more frequent exacerbation of asthma requiring systemic corticosteroids and/or hospitalization. They used a significantly greater mean daily dose of inhaled steroids compared to other patients. CONCLUSION Patients with monovalent IgE allergies to molds are at a higher risk for asthma than patients with other allergies. Their asthma is often more intense and less controlled compared to that of patients with other types of allergies.

A case of lipoatrophic panniculitis in a 2-year-old boy

Lipoatrophic panniculitis is generally a rare condition affecting mainly children, sometimes associated with connective tissue diseases [1, 2]. There are also reports about this condition occurring in adults [3]. This idiopathic, rarely reported panniculitis is presumed to have an autoimmune pathogenesis. A histopathological analysis reveals lobular panniculitis with fat necrosis and an associated inflammatory infiltration. Other histological findings are a focally increased number of lymphocytes rimming the adipocytes and infiltration of vascular walls by mildly atypical lymphoid cells [4]. Clinical and histopathological features lead to diverse diagnostic considerations like subcutaneous panniculitis-like T-cell lymphoma, Weber-Christian disease or Rothman-Makai syndrome [5]. We present a 2-year-old boy with no clinical or laboratory features of connective tissue disease who presented a progressive appearance of annular atrophic plaques with erythema on the right ankle. Skin lesions were about 2–3 cm in diameter with palpable loss of subcutaneous tissue (Figure 1). The patient was referred to the Chair and Clinical Department of Internal Diseases, Dermatology and Allergology in Zabrze after several consultations in other dermatology and rheumatology departments, with a suspicion of morphea, granuloma annulare orlipodystrophy. All blood tests like blood count, biochemical analysis, antinuclear antibodies and inflammatory markers were normal. Also X-ray of the lower limb was correct. There was no anamnesis of arthritis, thyroid gland abnormalities or fever. The first histopathological examination revealed acanthotic epidermis, collagen fiber protrusion, reduction of elastic fibers and in subcutaneous tissue – panniculitis. On the basis of the histological image, morphea profunda was suspected. However, the clinical picture with no immunological markers of connective tissue disease was still thought-provoking. The boy was treated with topical and systemic steroids for 6 months, and also with pentoxifylline and naproxen with no significant improvement. The second histopathological examination showed lymphocytes and histiocytes infiltration in the deep layers of dermis and subcutaneous tissue, in fatty tissue atrophy and inflammatory infiltration with histiocytes, lipofages similar to Touton cells and lymphocytes (Figure 2). On the basis of analyzed data, clinical and histopathological examination we identified lipoatrophic panniculitis. The appearance of new disease outbreaks required different treatment. Methotrexate (MTX) in an oral dose of 6.125 mg once a week (10 mg/m2/week) was administered for 10 weeks. A good tolerance of medication, on the basis of clinical condition and biochemical parameters monitoring, was noticed. We observed total suppression of the process with no further progression of skin lesions during 2 years of observation. Figure 1 Skin lesions before the treatment Figure 2 Histopathological examination – lipoatrophic panniculitis We present the case to describe clinical and diagnostic difficulties in our young patient with good clinical response to methotrexate (MTX) treatment. Although lipoatrophic panniculitis is a rare condition it should be considered particularly in the case of children. Panniculitis in children is a heterogeneous group of diseases, and so is in adults; it is characterized by inflammation of the subcutaneous and fatty tissue. Only a few types of panniculitis are found in childhood only, such as fat sclerosis of the newborn, while the vast majority of other types may be found both in the pediatric age and in adults [6, 7]. Lupus panniculitis, cold panniculitis, panniculitis in Behcets disease, and post-steroid panniculitis are mainly observed in adults [8]. There are also few rare forms of panniculitis, such as eosinophilic panniculitis or subcutaneous panniculitis T-cell lymphoma, which often give diagnostic difficulties but also mainly occur in adults [9]. Lipoatrophic panniculitis is most frequently observed in infants and children. Its clinical features are erythematous nodules and plaques followed by circumferential atrophy of the distal lower extremities, sometimes connected with fever, juvenile arthritis, or Hashimoto disease. In the diagnostic process it should be differentiated with all forms of panniculitis. Immunological, endocrine abnormalities and morphea or lupus profundus should be excluded. In our case, the patient was previously diagnosed with morphea, probably because of lack of experience in recognizing lipoatrophic panniculitis, which is rare. As described by some authors, it may be difficult to distinguish between lipoatrophic panniculitis and panniculitis of Weber-Christian or its variant – Rothmann-Makai panniculitis [10]. Histopathological examination of the deep skin biopsy seems to be crucial for differentiation. Also treatment of lipoatrophic panniculitis may be challenging. There are few reports concerning therapy with steroids, hydroxychloroquine or methotrexate (MTX) [11]. However, there are no clear indications for childrens therapy. Lipoatrophic panniculitis should be considered in infants and young children with clinical features of panniculitis and fat atrophy without clinical or serologic evidence of connective tissue disease. Methotrexate may be considered as a good treatment when systemic therapy is essential.

Analysis of selected allergic reactions among psoriatic patients

Introduction Psoriasis is a chronic and recurrent inflammatory skin disease. The aetiology is still unknown in spite of numerous scientific researches. There is very little evidence which does not provide enough knowledge about allergic reactions in psoriatic patients. Based on the fact that the epidermal barrier damage allows different allergen types to penetrate into deep layers of epidermis and skin, we can assume that it may lead to immunological reactions. Aim To investigate the allergic reaction indicators and hypersensitivity assessment about contact, inhalant and food allergens. The results were analysed with regard to clinical disease indicators and progression stage of dermal lesions. Material and methods Eighty patients with psoriasis were examined. The concentration of total IgE antibodies and allergen specific IgE antibodies (asIgE) were analysed. Standard epidermal tests and atopy patch tests were performed. All the patients were estimated for their dermatological condition based on the PASI scale. The control group consisted of 50 patients without psoriasis and allergic history. Results Significantly higher concentration of total E immunoglobulin has been stated in the patients with psoriasis. Higher concentrations of specific allergic IgE antibodies were more often observed in the examined group but the most frequently observed values were present in 1–3 class. The most common airborne allergens were birch, artemisia, timothy and rye pollens. There have not been any significant statistical differences in the case of positive epidermal test results. Conclusions There is slightly expressed hypersensitivity in psoriatic patients. This hypersensitivity degree correlates with the intensification of symptoms.

Prolonged effect of allergen sublingual immunotherapy to grass pollen

ABSTRACT Background: The prolonged effect of allergen immunotherapy is unknown, especially in older patients. Objective: The three-year effect of sublingual allergen-specific immunotherapy (AIT) to grass pollen on elderly patients with allergic rhinitis was analyzed. Methods: Thirty-eight elderly patients (63.18 ± 3.12 yrs.) underwent AIT to grass pollen, were monitored for three years and were compared to a placebo group. AIT was performed with the use of an oral Staloral 300 SR grass extract (Stallergens Greer, London, UK) or a placebo. Symptoms and medication scores, represented by the average adjusted symptom score (AAdSS), the serum level of IgG4 to Phl p5 and the quality of life were assessed immediately after AIT and three years later. Results: After AIT, the AAdSS was significantly decreased and remained lower than in the placebo group during the three years after AIT. Serum-specific IgG4 against Phl p5 increased during the AIT trial in the study group. For the three years of observation after AIT, there were no significant changes in specific IgG4 levels against the analyzed allergens in comparison to the results immediately after AIT. The quality of life, based on the Rhinoconjunctivitis Quality of Life Questionnaire, was significantly decreased in patients who received AIT, from 1.83 (95%CI: 1.45–1.96) to 0.74 (95%CI: 0.39–1.92) (p < 0.05) to 0.82 (95%CI: 0.45– 1.04) three years after AIT. Conclusion: A prolonged positive effect after AIT to grass pollen was observed in elderly patients with allergic rhinitis. Further trials are needed to confirm this effect.

The presence of fungal floras in sinuses in chronic sinusitis patients with polyps

Several fungal species are known to cause severe respiratory and cutaneous diseases. The aim of this work was to analyze the fungal flora in maxillary sinuses in patients suffering from chronic sinusitis with polyps. Twenty five patients (11 woman, 14 man) who underwent endoscopic surgical procedures were included into the study. During the operation, the smear from the maxillary sinus were obtained for the incubation. In 6 persons fungal floras was present.