Vol 44, No 1 (2016)

DERMATOLOGY

DEVELOPMENT OF AZATHIOPRINE-BASED TREATMENT REGIMEN FOR PATIENTS WITH STEROID RESISTANT PEMPHIGUS BASED ON ASSESSMENT OF MOLECULAR MECHANISMS AT THE POST-RECEPTOR LEVEL

Olisova O.Y., Shimanovskiy N.L., Dukhanin A.S., Teplyuk N.P., Lepekhova A.A.

Abstract

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.

Almanac of Clinical Medicine. 2016;44(1):6-12
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EPSTEIN-BARR VIRUS AND CYTOMEGALOVIRUS: IS THEIR ROLE IN PEMPHIGUS REALLY INCIDENTAL? A PRELIMINARY REPORT

Makhneva N.V., Syuch N.I., Voronova V.V., Beletskaya L.V.

Abstract

Background: Epstein-Barr (EBV) and cytomegaloviral (CMV) infections are among most prevalent in the population worldwide that are associated with autoimmune processes. However, conflicting data of the studies on the role of herpes viral infections in the etiology of autoimmune pemphigus does not allow for reliable recognition of these viruses as triggers in the development and course of this bullous dermatosis. Aim: To assess specific IgM and IgG antibodies to herpes virus infections in patients with autoimmune pemphigus. Materials and methods: Serum samples from 15  patients with autoimmune pemphigus were analyzed by chemoluminescent immunoassay. Results: In the serum samples of 14/15 (93.3%) patients with autoimmune pemphigus we found specific IgG antibodies to nuclear and capsid EBV proteins at the levels of 30.7 to 600 U/mL (median, 147.5 [102.62; 313.25] U/mL) and from 33.5 to 567 U/mL (median, 186 [85.95; 492.5] U/mL), respectively. Specific IgG antibodies to the EBV early protein were found only in 6.7% of cases. In all patients, there were no specific IgM antibodies to EBV capsule antigens. All patients (100%) had specific IgG anti-CMV antibodies in the range from 64.5 to 138 U/mL (median, 103.5 [94.83; 113.75] U/mL). In 30% of cases, there were specific IgM anti-CMV antibodies at titers of 11 to 12.3 U/mL (median, 5 [5; 9.5] U/mL). Conclusion: The results of the preliminary study showed that 93.3%  of autoimmune pemphigus cases have an underlying chronic infection caused by EBV and CMV. The finding of the high titers of IgG anti-EBV and anti-CMV antibodies allows to conclude that the association of these viruses with the bullous dermatosis is not just a chance. It makes further research undoubtedly necessary. Its results would draw more accurate conclusions on the role of EBV and CMV in the pathogenesis of autoimmune pemphigus and to find new perspectives in the treatment of patients with this life-threatening disease.

Almanac of Clinical Medicine. 2016;44(1):13-17
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EXTRACORPOREAL PHOTOCHEMOTHERAPY IN PSORIASIS AND PSORIATIC ARTHRITIS

Yakubovskaya E.S., Molochkov V.A., Kil'dyushevskiy A.V., Karzanov O.V.

Abstract

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.

Almanac of Clinical Medicine. 2016;44(1):18-27
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THE USE OF LOCAL LONG-WAVE INFRARED IRRADIATION IN THE COMBINATION TREATMENT OF LOCALIZED SCLERODERMA

Sekirin A.B., Smirnova S.N., Sukhova T.E., Maybrodskaya A.E.

Abstract

Background: Localized scleroderma often results in irreversible cosmetic abnormalities and if advanced, to organ dysfunction and disability. Pharmacological treatment is not effective enough and can cause adverse events and complications. Due to this fact, much attention is paid to non-medical approaches to this disorder that would be able to exert positive clinical and patho-physiological effects and potentiate the effects of medical treatment. Aim: To evaluate the effects of local long-wave infrared irradiation on the course of localized scleroderma and to assess therapeutic efficacy of this method combined with conventional pharmacological treatment. Materials and methods: Fifty five (55) patients with localized scleroderma were included into the study. The patients from the control group (n = 20) were administered conventional medical treatment for 14  to 20  days, including antibacterials, proteolytic enzymes, calcium antagonists, antioxidants, topical vasculoprotectors + microcirculation correctors, as well as applications of corticosteroids. The patients from the main group (n = 35), in addition to conventional medical treatment, were administered local long-wave infrared irradiation of the lesions (wavelength 4  to 16  mcm, once daily for 10  days). We assessed changes in edema and hyperemia on the borders of the lesion, the degree and extent of the process with a modified scoring system mRODNAN Skin Score, as well as microcirculatory vasculature by means of Spectrotest. Results: Compared to the control group, the patients with localized scleroderma who, in addition to conventional medical treatment, were administered local long-wave infrared irradiation, showed a  bigger reduction of mRODNAN index (2.2 ± 0.1 and 6.3 ± 0.5, respectively, р < 0.05), of oxygen saturation within the lesions (0.646 ± 0.04 and 0.9 ± 0.001 units, р < 0.05) and an increase of blood flow volume in the microcirculation (0.23 ± 0.045 and 0.091 ± 0.002 units, р < 0.05). They also demonstrated a quicker clinical improvement that was obvious at day 14 ± 2.3 (р < 0.05). In the control group, the clinical improvement was seen only at day 20 ± 4.2 (р < 0.05), with only a tendency towards a  decrease in oxygen saturation within the lesions (from 0.87 ± 0.01 to 0.817 ± 0.005) and an increase of blood flow volume in the micro-circulation (from 0.086 ± 0.004 to 0.1 ± 0.003 units). The conventional medical treatment did not result in full resolution of the local scleroderma elements, this was confirmed by the results of assessment with mRODNAN index (mean value before treatment in this group was 6.4 ± 0.5, after treatment, 5.3 ± 0.2, р ≥ 0.05). Conclusion: The study proved the clinical efficacy of local long-wave infrared irradiation in the combination treatment of localized scleroderma. This effect was seen in the normalization of microcirculation parameters, increase of blood flow, decrease of oxygen saturation within the lesions reflecting active reparation, as well as in better clinical efficacy and more quick effect.

Almanac of Clinical Medicine. 2016;44(1):28-32
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THE USE OF CONFOCAL LASER SCANNING MICROSCOPY IN THE DIAGNOSTICS OF BULLOUS PEMPHIGOID OF LEVER

Olisova O.Y., Teplyuk N.P., Tkachenko S.B., Varshavskiy V.A., Zaydenov V.A., Allenova A.S.

Abstract

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.

Almanac of Clinical Medicine. 2016;44(1):33-38
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SEGMENTAL FORMS OF HAILEY-HAILEY DISEASE AND THEIR MANIFESTATIONS: CLINICAL CASES

Makhneva N.V., Chernysh E.S., Beletskaya L.V.

Abstract

Hailey-Hailey disease (familial benign chronic pemphigus by Gougerot-Hailey-Hailey) is a  rare autosomal dominant skin disorder characterized by mostly symmetric skin lesions in the skin fold areas. However, segmental distribution of skin lesions in cases of epigenetic or genomic mosaicism can also occur. It is known that it is caused by a de novo post-zygotic mutation that appears at an early stage of embryogenesis both in somatic and in germinative cells. Depending on allele status, there are two types of segmental forms of autosomal dominant disorders. The article presents two clinical cases with manifestation of segmental form of Hailey-Hailey disease type 1 and type 2. These examples demonstrate not only the variety of clinical signs of the disease, but also specific features of this gene dermatosis and the prognosis of its inheritance in subsequent generations.

Almanac of Clinical Medicine. 2016;44(1):39-44
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A CASE OF REACTIVE POST-ENTEROCOLITIC ARTHRITIS (REITER’S SYNDROME)

Molochkov A.V., Molochkov V.A., Petrova M.S., Belousova E.A., Mylov N.M., Seliverstova T.R., Sekirin A.B.

Abstract

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. 

Almanac of Clinical Medicine. 2016;44(1):45-51
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THE ANGIOTROPHONEUROSES. ERYTHROMELALGIA IN A 11-YEAR OLD CHILD

Tamrazova O.B., Molochkov A.V., Koren'kova O.V., Novikov K.A.

Abstract

The article deals with angiotrophoneuroses, a large group of heterogenous disorders with an underlying dysfunction of vascular innervation. A  current classification of vegetovascular neuroses, their triggers and clinical manifestations are described. The main attention is paid to a  rare disease, erythromelalgia that is сharacterized by acute attacks of dilatation of small vessel of the extremities with associated severe pain, skin hyperemia and edema. We present a  clinical case of primary erythromelalgia in a 11-year old child. The complexity of diagnostics and treatment of the case were related to a combination of classical manifestation of the disease with advanced mental problems resulting in autoagressive behavior.

Almanac of Clinical Medicine. 2016;44(1):52-57
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DERMATO-ONCOLOGY

CHARACTERISTICS OF PROLIFERATION AND INTERCELLULAR ADHESION IN PRE-CANCEROUS AND MALIGNANT EPITHELIAL SKIN TUMORS

Khlebnikova A.N., Gurevich L.E., Selezneva E.V., Obydenova K.V., Sedova T.G., Kuntsevich Z.S.

Abstract

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.

Almanac of Clinical Medicine. 2016;44(1):58-63
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PHOTODYNAMIC THERAPY OF TYPICAL AND ATYPICAL KERATOACANTHOMA

Molochkova Y.V., Kuntsevich Z.S., Sukhova T.E., Dibirova S.D., Galkin V.N., Ivanov S.A., Romanko Y.S.

Abstract

Background:  Photodynamic  therapy  (PDT) has  shown  its  clinical  efcacy  in  the  treatment of  keratoacanthoma.  However,  the  published data  is  scarce  and  contradictory.  Methods  of a photosensitizer administration and irradiation doses  depending  on  the  type  of  keratoacanthoma have not been defned. Aim: To develop the  diferentiated  approached  to  PDT  for  typical  and  atypical  keratoacanthoma  by  variation of  the  light  density  while  using  of  a  chlorine photosensitizer.  Materials  and  methods:  We assessed and treated 36 patients with cytologically and/or histologically confrmed solitary keratoacanthomas,  among  them  22  patients  with typical  and  14  patients  with  atypical  ones.  In 12  patients,  persistent  keratoacanthomas  were diagnosed,  in  1,  a  gigantic  one  and  in  1,  a  centripetal one. Each patient was administered one session of PDT with an intralesional administration  of  a  photosensitizer  Radachlorin  at  a  dose of  0.75  mL/cm3.  The  source  of  laser  irradiation was a medical laser device LAMI (with the wave- length of 662 ± 3 nm, the power of irradiation at the edge of the light guide, 2 Wt). The absorbed light  density  was  50  J/cm2  for  typical  keratoacanthomas  and  300  J/cm2  for  atypical  ones. 70 Results: After the treatment, in 32 (89%) of patients  the  tumor  completely  regressed  within one month (26 ± 1.3 days). In 4 patients (all with atypical  keratoacanthomas)  the  tumors  did  not regress within one month and was removed surgically with the 3 mm margins of obviously normal skin. At the site of former tumors, there were areas of atrophic scarring (26 cases, in 4 patients, with  hyperpigmentation)  or  with  normotrophic scarring (10 patients) that were cosmetically acceptable. Within the next 2 years of the follow-up no  relapses  were  observed.  Conclusion:  Thus, we  proposed  an  efective  method  of  diferentiated approach to PDT of typical and atypical keratoacanthomas  based  on  one  PDT  session  with an  intralesional  administration  of  Radachlorin at a dose of 0.75 mg/cm3 of the tumor, with the intensity of irradiation of 0.39 Wt/cm2. The light dose  density  for  typical  keratoacanthomas  is 50 J/cm2 and for atypical ones, 300 J/cm2. 

Almanac of Clinical Medicine. 2016;44(1):64-70
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INVERTED FOLLICULAR KERATOSIS: A RETROSPECTIVE ANALYSIS OF 50 CASES

Sedova T.G., El'kin V.D., Lysov A.Y., Kopytova E.A.

Abstract

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. 

Almanac of Clinical Medicine. 2016;44(1):71-77
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COMPARATIVE ASSESSMENT OF THE EFFICACY OF PHOTODYNAMIC THERAPY OF BASAL CELL SKIN CANCER WITH THE INTRALESIONAL ADMINISTRATION OF RADACHLORIN AND FOTODITAZIN

Sukhova T.E.

Abstract

Background: Photodynamic therapy (PDT) is increasingly used for non-invasive destruction of basal cell skin cancer mediated by a photochemical reaction. There is no evidence-based data on its efficacy. Aim: To compare the objective response of basal cell skin cancer of various clinical types, stages, histological types, course and localization to PDT with the intralesional administration of photosensitizers Radachlorin and Fotoditazin. Materials and methods: From March 2007 to March 2010, the study recruited 74  patients with primary and relapsing solid basal skin cancer (ulcerated, 40.5%  of patients, superficial, 24%, nodular, 21.5%, scleroderma-like, 14%), stage  Ι–ΙI (mostly Т₂N₀M₀); with localization that was unfavorable in terms of relapses and inconvenient for treatment application. The tumors were of a uniform complex histological type and of a morphea type. The patients were administered one course of PDT with an intralesional administration of chlorine photosensitizers. The group I (n=45) was administered Radachlorin (0.5–1 mL per 1 cm² of the tumor surface), group II (n=34) was administered Fotoditazin (0.3–0.5  mL per 1  cm² of the tumor surface). For all patients the light dose was chosen at 300 J/cm², the light source being the medical laser device LAMI with a wave length of 662±3 nm, class II А. Clinical and cytological regression of the lesions at 3 months after treatment was chosen as a  primary study endpoint. The secondary endpoints were a  stable clinical and cytological response at 12 months after treatment. Thereafter, a relapse-free period was assessed annually up to 5 years after treatment. In addition, adverse reactions to treatment were registered up to 2 months and cosmetic results were assessed at 12 months after PDT. The treatment results were assessed in all patients. Results: Complete regression of basal cell skin cancer was found in 43 (95.5%) of patients from the group I  and in 31  (91.2%) patients from the group II. Partial regression was seen in 2 (4.5%) and 3  (8.8%) of patients, respectively; these patients were subsequently cured by repeated courses of PDT. In both groups, there was no difference in the early treatment results in patients with various clinical forms of basal cell skin cancer at Т₁N₀M₀ (p>0.05). There was a  significant improvement in the treatment results for the ulcer type of the tumor at stage T₂N₀M₀: 92.8%  in the group  I  and 77.8% in the group II (р<0.05). The long-term follow-up  showed  a  5-year  relapse-free  disease  in 42 (97.7%) of 43 cured patients of the group I and in 30 (96.8%) of 31 patients in the group II. Adverse events  were  seen  in  all  patients;  however,  they were  limited  to  short-term  unavoidable  adverse reactions such as skin hyperemia, edema, exudation, paresthesia and pain. Eight (8) per cent of patients from the group I and 6% from the group II had  their  blood  pressure  values  increase.  An  excellent  and  good  cosmetic  result  after  PDT  was observed in the majority of patients (74.4% in the group  I  and  77.4%  in  the  group  II).  Conclusion: PDT with the intralesional administration of pho- tosensitizers Radachlorin and Fotoditazin is an effective treatment approached for any clinical and morphological type of basal cell skin cancer. It is associated with minimal adverse reactions and has an acceptable cosmetic result.

Almanac of Clinical Medicine. 2016;44(1):78-87
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THE EXPERIENCE OF TREATMENT OF MULTIPLE BASALIOMA IN GORLIN-GOLTZ SYNDROME

Tret'yakova E.I.

Abstract

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. 

Almanac of Clinical Medicine. 2016;44(1):88-95
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ACITRETIN IN THE TREATMENT OF GRZYBOWSKI TYPE ERUPTIVE KERATOACANTHOMA

Kuntsevich Z.S., Molochkova Y.V., Bobrov M.A., Khlebnikova A.N., Dibirova S.D.

Abstract

The article describes a  case of successful treatment of multiple eruptive keratoacanthoma of Grzybowski in a 82-year old woman with concomitant advanced heart disease and chronic gastritis. The tumor was diagnosed in 1 of 256 patients with keratoacanthoma who attend our clinic, i.e. in 0,39% keratoacanthoma cases in general and in 0,96% among atypical keratoacanthomas. HLA-A2 gene characteristic for atypical keratoacanthomas was found in this patient. Acitretin was administered for 3 months at a  daily dose of 20 mg. The treatment resulted in a  full regression of the elements with residual areas of scarry atrophy and/or depigmentation. Flattening of the elements was obvious after 2 weeks. The patient tolerated the treatment well. 

Almanac of Clinical Medicine. 2016;44(1):96-102
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TREATMENT OF THE TUMOR STAGE OF MYCOSIS FUNGOIDES WITH EXTRACORPOREAL PHOTOCHEMOTHERAPY (A CASE DESCRIPT

Molochkov V.A., Kil'dyushevskiy A.V., Karzanov O.V.

Abstract

The article describes treatment experience with a  tumor stage of mycosis fungoides patient treated with extracorporeal photochemotherapy that showed high clinical efficacy. The patient responded with significant regression of the skin elements after two courses of extracorporeal photochemotherapy. The follow-up period was 5 months and is ongoing, as is the treatment.
Almanac of Clinical Medicine. 2016;44(1):103-106
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A CASE OF PARANEOPLASTIC EROSIVE ULCERATIVE LICHEN PLANUS RUBRUM ASSOCIATED WITH A RECTAL ADENOCARCINOMA

Molochkov V.A., Bobrov M.A., Amkhadova M.A., Molochkova Y.V., Petrova M.S., Kul'bachinskiy N.V.

Abstract

The erosive ulcerative form of lichen planus rubrum localized on the oral mucosa is the most resistant to treatment from all types of the disease. It becomes malignant in 3% of cases and quite often is of a paraneoplastic character. We present a clinical case of an aggressive and resistant to treatment paraneoplastic erosive ulcerative lichen planus rubrum of the oral mucosa and the vermilion zone in a patient with polygonal papules typical for this dermatosis. The papules resolved after surgical removal of colorectal cancer tumor that was diagnosed at an early stage (adenocarcinoma in situ). We draw attention to the necessity of timely and careful assessment of patients with erosive ulcerative lichen planus rubrum for malignant neoplasms.
Almanac of Clinical Medicine. 2016;44(1):107-113
pages 107-113 views

VENEREOLOGY

ON THE ASSESSMENT AND TREATMENT OF PATIENTS WITH CHRONIC PROSTATITIS IN PERSISTENT UROGENITAL CHLAMYDIOSIS

Molochkov V.A., Aleshkin V.A., Skirda T.A., Karaulov A.V., Molochkova Y.V., Antonova E.V.

Abstract

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. 

Almanac of Clinical Medicine. 2016;44(1):114-120
pages 114-120 views

AN EXAMPLE OF A MULTIFACETED APPROACH TO DIAGNOSTICS AND TREATMENT OF UROGENITAL REACTIVE ARTHRITIS (REITER’S DISEASE)

Molochkov A.V., Petrova M.S.

Abstract

Urogenital reactive arthritis (Reiter's disease) is a  vital interdisciplinary problem due to multiple symptoms of the disease, their appearance at different times, inadequate clinical alertness of specialist, as well as to the necessity of significant efforts both from the part of the doctor and the patient during the process of multifaceted diagnostics. Based on a  clinical case, we demonstrate a classical clinical manifestation of urogenital reactive arthritis that was initially administered incongruent symptomatic treatment resulting only to temporary attenuation of one of the symptoms. We illustrate a comprehensive approach to management, assessment and treatment of the patient based on the causal factor, pathophysiologic characteristics of the disease and immunologic criteria, with the use of immunomorphological skin investigation, photopheresis and lymphotropic therapy.
Almanac of Clinical Medicine. 2016;44(1):121-127
pages 121-127 views

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