Vol 44, No 1 (2016)

Background: Autoimmune pemphigus is the most severe skin and mucous membranes disorders with production of IgG autoantibodies to desmogleins 1 and 3. Administration of systemic corticosteroids may help to abrogate active signs of pemphigus. However, some patients do not give an adequate response to systemic glucocorticosteroid monotherapy, as well as to their combination with immune suppressants and cytostatic agents. Aim: To develop an azathioprine-based treatment regimen for patients with autoimmune pemphigus resistant to steroids. Materials and methods: At the first step of development of a treatment regimen for patients with steroid-resistant pemphigus we analyzed retrospectively a clinical database on 23 patients who had been treated from 2000 to 2014 and whose treatment regimen included azathioprine, in addition to systemic glucocorticosteroids. At the second step, from 2013 to 2015, we assessed and treated with the azathioprine-based regimen 24 patients with autoimmune pemphigus, 14  of them being steroid resistant and 10, steroid sensitive (control group). To assess molecular mechanisms of steroid resistance at the post-receptor level (effect of prednisolone on incorporation of ³Н-uridine into lymphocyte mRNA, changes of intracellular levels of nuclear transcription factor NF-κB) we used a  real-time polymerase chain reaction, radioisotope method and liquid scintillation radiometry. Results: At the first step, we developed an azathioprine-based treatment regimen for patients with steroid resistant autoimmune pemphigus. Initial dose of azathioprine was 150 mg daily. After achievement of response, the dose was decreased to 100 mg daily. When the dose of systemic glucocorticosteroids was decreased to 20  mg daily, the dose of azathioprine was decreased to 50 mg daily, thereafter steroid resistant patients were taking azathioprine at a dose of 50 mg daily from 3  months to 2.5  years. Investigation of molecular mechanisms at the second step of the study showed that in 28%  of steroid resistant patients there was a decreased incorporation of ³Н-uridine into lymphocyte mRNA under prednisolone treatment with an increase in synthesis of total mRNA in lymphocytes (range, from 68.67 to 78.35%, р < 0.05). Compared to the control group, in all steroid resistant patients (n = 14), an increased NF-κB gene expression in lymphocytes was found (range, from 65.39 to 86.17%  and from 88.8  to 98.61%, respectively, р < 0.05). The combination therapy with systemic glucocorticosteroids and azathioprine in steroid resistant patients resulted in a  decrease in intracellular NF-κB gene expression (p < 0.01), which underlies the steroid-sparing effect of azathioprine. Conclusion: We demonstrated a statistically significant suppression of NF-κB gene expression in the cases of its high baseline levels before combination therapy in patients with autoimmune pemphigus. The steroid-sparing effect of azathioprine allows for its effective use in steroid-resistant pemphigus.

Background: Psoriasis is the most prevalent chronic dermatosis of an autoimmune origin that is characterized by increasing incidence of both severe clinical forms and complications, the most threatening of which is psoriatic arthritis. Its treatment includes aromatic retinoids, immunosuppressant therapies (immunosuppressant agents, glucocorticosteroids), PUVA-therapy and other methods. However, these are insufficiently effective in clinical practice and are frequently associated with serious adverse reactions and complications. Aim: To increase the efficacy of treatment for psoriasis associated with psoriatic arthritis by means of incorporation of a new immunobiological method, the extracorporeal photochemotherapy (EPCT) into the standard treatment protocol. Materials and methods: We conducted a  prospective cohort study with an active control. Seventy patients with various forms of psoriasis associated with psoriatic arthritis were randomized with stratifi-cation into two groups. The patients of the main group (n = 35) were treated with EPCT, whereas those from the control group (n = 35) received the standard treatment. The EPCT method included isolation of mononuclear cells preliminary sensitized with 8-methoxypsoralen with a cell separator Haemonetics MCS+. After the cell suspension was treated with UV А  (λ = 320–400  nm), it was re-infused to the patient. The treatment course included 4 sessions performed every other day. Results: The analysis of clinical efficacy of EPCT in the combination treatment of psoriasis associated with psoriatic arthritis demonstrated that in the majority of cases a  significant therapeutic effect was achieved. The mean PASI index decreased from 28.5 ± 1.63 to 6.6 ± 1.7 (p < 0.05), the activity of psoriatic arthritis (DAS score), from 3.7 ± 0.35 to 1.7 ± 0.36 (p < 0.05). This significant treatment effect was associated with a  decreased correlation between expression of activation molecules HLADr by natural killer cells (r = 0.6, p < 0.05) and of integrin adhesion molecule CD11b (r = 0.7, p < 0.001). Restoration of apoptosis of autoaggressive cytolitic cells (CD8) determined an improvement in homeostatic imbalance between activation and tolerance. Conclusion: Incorporation of EPCT into the standard protocol of treatment of patients with psoriasis associated with psoriatic arthritis is considered to be highly effective and pathophysiologically based treatment method that allows for cessation of the pathological process within a  short time, with further regression of clinical symptoms. The treatment effect is explained by correction of immune regulatory mechanisms that provide restoration and maintenance of immune homeostasis.

Diagnostics of autoimmune bullous dermatoses, including bullous pemphigoid of Lever that is characterized by a large variety of clinical manifestations and in many cases by severe course and high mortality, remains one of the most complicated problems in dermatology. High diagnostic error rates are to be explained not only by variability of the forms of bullous pemphigoid of Lever, but also by insufficient accuracy of existing diagnostic methods, as well as by the complexity of their implementation. Non-invasive diagnostic methods have an undoubted advantage because they allow for prompt results of the assessment and therefore to fasten the initiation of therapy and to avoid damage to the skin, which is extremely important for patients with an autoimmune bullous dermatosis. The most accurate among non-invasive methods is a confocal laser scanning microscopy. The article describes the main features of the method and its potential application for the diagnosis of bullous pemphigoid of Lever with two clinical cases.

Reactive arthritis is an autoimmune disease from the  group  of  seronegative  arthritis  known  as spondyloarthropathy.  Two  types  of  the  disease are  designated  by  this  term,  namely  post-enter- itic  (Reiter's  syndrome)  and  venereal  (urogenital) (Reiter's  disease).  Irrespective  of  the  infectious agent,  both  types  of  the  disorder  can  be  associated  with  various  symptoms  including  skin  and mucosal lesions and heart. However, the post-enteritic  type  of  reactive  arthritis  is  associated  also with  intestinal  problems  and  the  venereal  one (mostly  being  of  chlamydial  origin),  –  with  gen- itourinary  disorders.  Due  to  highly  variable  clinical  manifestations  of  reactive  arthritis,  patients frequently  receive  only  symptomatic  treatment that  temporarily  eliminates  some  symptoms.  We describe a clinical example of diagnostic approach to this complex disease, that allowed for putting the  defnite  diagnosis  and  perform  diferential diagnosis  with  other  similar  disorders  including urogenital  reactive  arthritis.  This  paper  could  be of interest for practitioners in various specialties, frst, for dermatovenereologists, rheumatologists, gastroenterologists,  internists  and  rehabilitation specialists. 

Background: Differential diagnostics between actinic keratosis which is one of pre-cancerous skin diseases, and intra-epidermal squamous cell skin cancer (or Bowen's disease) could be difficult in some cases even with morphological examination. The study on molecular characteristics of pre-cancerous skin disorders would allow for more accurate diagnostics and assessment of prognosis. Aim: To study proliferative activity of keratinocytes and E-cadherin expression on cell membranes in actinic keratosis and in Bowen's disease, with identification of differential diagnostic criteria. Materials and methods: We performed an immunohistochemistry study with anti-Ki-67 and anti-Е-cadherin monoclonal antibodies in skin bioptates of 23 patients with actinic keratosis and 10 patients with Bowen's disease. Results: The mean proliferation index in actinic keratosis without the bowen-like loci was 30.9 ± 11.4% (range, from 11.5 to 48.4%), and in actinic keratosis with the bowen-like loci, 40.3 ± 8.6% (range, from 31 to 57.6%). In both groups, E-cadherin expression in all cases (100%) was located in cell membranes. The mean proliferation index in Bowen's disease was 44.7 ± 8.2% (range, from 33.3 to 60%). In 48.2% of Bowen cells, abnormal type of E-cadherin expression (reduced membranous, membranous and cytoplasmatic and cytoplasmatic only). Conclusion: Actinic keratosis and Bowen's disease represent different stages of one and the same malignant process that have different proliferative cell activity and E-cadherin expression, which could be used as differential diagnostic markers.

Background:  Inverted  follicular  keratosis  (IFK) is a rare benign skin neoplasm that could be diffcult  to  diagnose.  Pathomorphological  verifcation is recognized as the main diagnostic method. Aim: To analyze retrospectively clinical data from 50 IFK cases and to identify morphological tumor characteristics depending on its histological type. Materials and methods: Based on data extracted from medical documentation and reports on skin biopsies from 50 IFK patients, we analyzed retrospectively  some  clinical  data  and  pathohistological characteristics of IFK. We investigated pathohistological particulars of the tumor, identifed its histological  types  and  the  main  morphological signs of the neoplasm. We assessed the following histological  criteria  of  IFK:  presence  and  degree of  inverted  structures,  hyperkeratosis,  parakeratosis,  lymphoid  infltrates  in  the  derma.  Results: The  majority  of  IFK  patients  were  women  (68%) of older age (61.5± 1.6 years). In 40% of cases the tumor was located on the head, mostly on the face (32%); less frequently on the skin of the back (12%) and shanks (12%). At histological assessment, most cases (88%) of IFK were of one type. The most frequent  were  papillomatous  (32%),  keratoacanthomatous  (26%)  and  solid  (20%)  histological  types. Inverted structures were found in all histological preparations  (100%  of  cases).  Epidermal  abnormalities were mostly seen as hyperkeratosis (94% of  cases),  parakeratosis  (84%),  acanthosis  (78%) and dermal lymphoid infltration (74%). Advanced dermal  vascularization  was  seen  only  in  keratoacanthomous  and  cystic-keratoacantomous  histological types (76.9 and 100% of cases) and was characterized  by  reactive  proliferation  of  dermal capillaries. Conclusion: Pathomorphological verifcation of IFK is based on identifcation of inverted structures in bioptates. The variety of histological manifestations of the tumor is to be explained by various types of cell diferentiation. 

Aim: To assess clinical efficacy of the treatment options for multiple basalioma in patients with Gorlin-Goltz syndrome. Materials and methods: We retrospectively analyzed the results of various treatments in 23  patients with the Gorlin-Goltz syndrome for the time period of 25  years. Four treatment groups were formed depending on the treatment method. In the group 1, 18 patients were cryodestructed, with elimination of 158  superficial and ulcer basaliomas T₁N₀M₀, T₂N₀M₀, T₃N₀M₀. In the group 2, 5  patients received photodynamic therapy, with removal of 78 superficial, nodular and ulcer basaliomas T₁N₀M₀, T₂N₀M₀, T₃N₀M₀. In the group 3, 3  patients were administered laser-induced thermic therapy with removal of 16  superficial basaliomas T₁N₀M₀. In the group 4, 5 patients received topical chemotherapy with Mardil Selen, with removal of 18  superficial and ulcer basaliomas T₁N₀M₀. As radiation sources for photodynamic and laser-induced thermic therapy we used laser equipment with copper vaporization and adjusted wave length Metalaz 1  and semiconductor infrared laser LAMI. The photodynamic therapy was administered with photosensitizers Photohem and Radachlorin. The results of treatment and relapse-free periods were assessed annually in all patients up to 5  years after treatment. Results: After cryodestruction, 83.3%  of patients with Gorlin-Goltz syndrome were cured (153  basaliomas) and additional 16.7%  improved. Relapses during the time period from one to three years were observed in 16.7% of patients. Nine (9) basaliomas relapsed. After photodynamic therapy, 80%  of patients (73  basaliomas) were cured and 20%  improved. Relapses from 1  to 3  years were observed in 20% of patients (2 basaliomas). After laser-induced thermic therapy 100%  of patients (16  basaliomas were cured), and relapses from 1  to 2  years were registered in 33%  of patients (4 basaliomas). After topical treatment with Mardil Selen 80% of patients (12 basaliomas) were cured and 20% of patients improved. Relapses from 1 to 3  years were seen in 20%  of patients (3  basaliomas). Conclusion: Taking into account the disease specifics and a wide range of treatments and non-invasive therapies, none of the suggested treatment approaches for multiples basalioma associated with the Gorlin-Goltz syndrome can reliably prevent the relapses. In addition to radical treatment, preventive administration of aromatic steroids is necessary. 

Background: Urogenital chlamydial infection is the most prevalent among sexually transmitted disorders that is associated with high rates of complications (chronic prostatitis, salpingoophoritis, etc.) and adverse outcomes, such as sexual and reproductive dysfunction. In the last years, the frequency of persistent antibiotic-resistant chlamydial infections has been persistently increasing that is diagnosed by immunoenzyme assay of IgG antibodies to the heat shock protein of chlamydia with a molecular weight of 60 KDa (HSP60) and by detection of secretory IgA to Chlamydia trachomatis in the semen plasma. Aim: To assess the rates of persistent chlamydial infection in patients with chronic prostatitis by measurement of serum IgG anti-HSP60 antibodies to C. trachomatis and presence of anti-chlamydial IgG in the semen plasma. Materials and methods: In a  prospective study we examined 18 patients with chronic prostatitis, aged from 21 to 58  years. The control group included 30 subjects without chlamydial urogenital disease. Clinical assessment included past history, instrumental investigations, ultrasound examination of prostate and semen vesicles. Serological tests were performed by immunoenzyme analysis in 4  test systems (“Medac”, Germany) to two antigens: a  genus-specific chlamydial lipopolysaccharide r-ELISA (anti-chlamydial IgM, IgG and IgA antibodies) and to the main outer membrain protein (МОМР) of C.  trachomatis (IgG and IgA). Anti-HSP60 antibodies were measured in the test system with HSP60-IgG-ELISA (“Medac”). The levels of secretory IgA in the seminal fluid were assessed with a  test system Chlamydia trachomatis-IgA-pELISA. Results: In 13 (72.2%) of 18 patients the chronic prostatitis was of chlamydial etiology, and in 7 (38.9%) of 18 patients there was an underlying persistent chlamydial infections with concomitant high levels of serum IgG anti-HSP60 C. trachomatis and presence of anti-chlamydial IgA antibodies in the semen plasma. In the control group, IgG anti-chlamydial antibodies were not found. Conclusion: The results obtained confirm the diagnostic value of anti-C. trachomatis IgA antibodies in identification of the etiology of inflammation in the male genital tract. They also indicate a high rate of persistent chlamydial infection in patients with chronic prostatitis and the utility of serology tests for IgG anti-HSP60 C.  trachomatis and anti-chlamydial IgA antibodies in the semen plasma.