Vol 49, No 8 (2021)
ARTICLES
Potential impact of viral skin diseases and other viral infections on the incidence and severity of COVID-19 in renal transplant patients
Abstract
Background: COVID-19 in solid organ transplant recipients is usually characterized by more severe disease course and is often associated with life-threatening complications. Identification of additional factors that may affect the risk and severity of the new coronavirus infection could have a significant impact on choosing a management strategy for renal graft recipients.
Aim: To evaluate the possibility of cross-immunity between skin manifestations of viral etiology and COVID-19.
Materials and methods: From May 2020 to February 2021 we examined 180 renal graft recipients with a history of transplantation from 2 months to 26.5 years. All patients were categorized into two groups: group I (n=68), those who had confirmed moderate or severe COVID-19 disease and group II (n=112), those without any history of clinical manifestations of the new coronavirus infection (including those with potentially asymptomatic disease). During the study period which lasted for 71 months on average (range, 2 to 318 months), laboratory workup was performed in all patients (on average, twice): dermatological examination and detection of serum antibodies to herpes simplex virus 1, 2, cytomegalovirus, human papilloma virus (HPV), Epstein-Barr virus, SARS-CoV-2.
Results: In recipients with HPV-associated skin manifestations, the incidence of COVID-19 was significantly lower than in recipients who did not have them – 30.4% (34/112) and 50% (34/68), respectively (p=0.011). The incidence of new coronavirus infection did not differ in the groups of patients with cutaneous manifestations caused by herpes simplex viruses type 1 and 2, and without them. Among recipients with Epstein-Barr virus seropositivity, there were significantly fewer cases of COVID-19 compared to seronegative patients – 26.2% (28/107) and 54.8% (40/73), respectively (p=0.0002).
Conclusion: HPV-associated dermal manifestations or serum Epstein-Barr virus-seropositivity in renal graft recipients is associated with lower incidence of moderate and severe COVID-19. Further studies are needed to confirm the possibility of cross-immunity against SARS-CoV-2 with other infections.
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Optimization of therapy in patients with lichen ruber planus by means of cranial electrotherapy stimulation
Abstract
Rationale: Taking into account the significance of psychogenic factor in the onset of lichen planus, its correction is advisable. Transcranial electric stimulation is promising, given its autonomous regulating, analgesic, antipruritic, reparative and regenerative, and immunomodulatory effects, in addition to the anti-stress one.
Aim: To assess the effectiveness of the combination therapy including cranial electrotherapy stimulation (CES) with lichen ruber planus.
Materials and methods: This was an open label, prospective, comparative study in 61 patients with common typical form of lichen ruber planus (39 (63%) women and 22 (37%) men) aged 18 to 74 years (mean age 41 ± 14.29 years). The duration of the disease was 11.88 ± 10.15 months (range, 1 to 42 months). The patients were adaptively randomized into two groups of similar gender distribution, age, and disease duration. The patients in the comparison group (n = 30) were treated conventionally in accordance with the Federal Clinical Guidelines (chloroquine, hydroxyzine, topical corticosteroids). The main group (n = 31) was administered similar therapy; however, instead of hydroxyzine, CES was performed. The duration of in-patient treatment in both groups was 14 days, with the follow-up lasting for up to 3 months. The results of treatment were assessed by dynamics of pathological changes of the skin (Index of Lichen Planus, ILP), impact of dermatosis on various domains of the patient’s life (Dermatology Life Quality Index, DLQI), changes in psychological status (Hamilton Anxiety Scale and Hamilton Depression Scale). In addition, the impact of pruritus on the patients' daily activities was assessed by Behavioral Rating Scores questionnaire (BRS).
Results: At baseline, there were no significant differences between the groups in ILP (p = 0.801), DLQI (p = 0.501), BRS (p = 0.521), Hamilton Anxiety Scale (p = 0.301), and Hamilton Depression Scale (p = 0.493). At the end of treatment, ILP in the CES group decreased 3.25-fold (p < 0.001), whereas in the group treated with conventional therapy the decrease was 2.1-fold (p < 0.001); DLQI decreased 2.5-fold (p < 0.001) and 1.8-fold (p < 0.001), respectively. The corresponding decreases of Hamilton Anxiety Scale in the treatment groups were 2.3-fold and 1.3-fold, respectively, and those in Hamilton Depression Scale – 2-fold and 1.6-fold, respectively (all p < 0.001). In addition, statistically significant intergroup differences were found for ILP (p = 0.04), DQLI (p < 0.001), Hamilton Anxiety and Depression scale scores (p = 0.021 and p = 0.006, respectively). As for the BRS changes, in both groups there was an equally significant (p < 0.001) decrease, but the intergroup differences were not statistically significant (p = 0.485).
Conclusion: The proposed combination therapy of patients with lichen ruber planus including CES has led to a decrease in the indicators of the skin process activity within a shorter time period than in the patients under conventional treatment. In addition, the patients of both groups showed normalization of psychological parameters and improvement in dermatological quality of life; however, only in the CES group, these changes were significant.
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Efficacy of narrowband phototherapy in the treatment of different forms of psoriasis with the predominant affection of palms and soles
Abstract
Background: Palmar-plantar psoriasis is characterized by a torpid course and resistance to conventional systemic treatments. Phototherapy is usually considered as an adjuvant treatment of a patient with psoriasis. The potential use of phototherapy as a basic treatment strategy in limited psoriasis, including its plantar-palmar localization, could be of interest.
Aim: To study the efficacy, safety and tolerability of the narrowband phototherapy (UVB 311 nm) in the treatment of different forms of psoriasis with predominant palmar-plantar involvement.
Materials and methods: We retrospectively analyzed the results of treatment of 77 in-patients admitted to the Department of Dermatology for treatment of various types of psoriasis with prevailing palmar and plantar lesions. The main group consisted of 42 patients who were administered combination therapy including topical corticosteroids, hepatic protectors, antihistaminic agents and, in addition, the narrowband phototherapy with a phototherapy device Dermalight 500-1 (Dr. Hönle Medizintechnik GmbH, Germany). The initial radiation doses were set without the determination of the minimal erythema dose, depending on the patient's skin type, in accordance with the guidelines from the manufacturer. At each consecutive session, the dose was increased by 0.06–0.3 J/cm². The sessions were conducted 5 times a week with a total of 14–21 sessions. The mean cumulative dose was 22.8 J/cm². The control group included 35 age-, gender- and psoriasis severity-matched patients who received the same treatments, except the narrowband phototherapy. The treatment efficacy was assessed by changes in the Palmoplantar Pustulosis Area and Severity Index (PPPASI). Clinical results of treatment were evaluated at day 10 after the treatment course had been completed.
Results: No serious adverse events were registered during the treatment. In the patients with psoriasis vulgaris and predominant palmoplantar lesions, receiving the narrowband phototherapy, the PPPASI reduction was higher than in the patients who received only conventional treatment (U-test, p = 0.015). A PPPASI decrease of ≥ 50% was observed in 83.3% (25/30) and 60% (15/25) of the patients, respectively. Clinical efficacy criteria were achieved in 66.6% (8/12) of the patients with palmoplantar pustular psoriasis receiving the combination treatment with phototherapy and in 40% (4/10) of the conventionally treated patients in the control group; however, the difference in the distribution of remission achievement was non-significant (U-test, p = 0.123).
Conclusion: The study has demonstrated the efficacy of UVB 311 nm narrowband phototherapy in the treatment of patients with psoriasis with predominant palmoplantar lesions. The results obtained make it possible to recommend the inclusion of the narrowband phototherapy UVB 311 nm at mean cumulative dose of 22.8 J/cm² into the standardized set of treatments of patients with psoriasis vulgaris with predominant palmoplantar lesions, not only as an adjuvant technique, but also as the main therapeutic strategy. The role of the narrowband phototherapy UVB 311 nm in the treatment of palmoplantar pustular psoriasis, as well as the dosing regimens of the radiation and determination of the necessary follow-up duration should be the subject of further studies.
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Evaluation of serum markers of the immune response and bone metabolism facilitates early detection of psoriatic arthritis in patients with psoriasis
Abstract
Relevance: Psoriatic arthritis (PA) is a severe complication of psoriasis, leading to progressive damage to the musculoskeletal system, a decrease in the quality of life and early disability. CASPAR criteria, widely used for PA diagnosis, are highly sensitive and specific. However, some patients with psoriasis score ≥ 3 with CASPAR criteria without an established PA diagnosis. At present, there is a search for PA biomarkers, which could mirror the stages of pathogenesis of joint and enthesis destruction in this disease.
Aim: To identify the most significant changes in biochemical parameters in patients with PA, that would be pathophysiologically associated with the disease.
Materials and methods: We performed an open label comparative parallel groupstudy in 60 patients with PA and 40 patients with psoriasis without PA. Clinical assessments included filling in the questionnaires, past history, dermatologist consultation, severity of psoriasis by PASI, and PA activity. Clinical chemistry examination included the levels of antibodies to citrullinated peptide, erythrocyte sedimentation rate, C-reactive protein (CRP), human leukocyte antigen HLA B27, immunoglobulins A, M, and G, complement system components C3, C4, circulating immune complexes (CIC), as well as bone metabolism parameters (calcium, phosphorus, magnesium, seromucoid, alkaline phosphatase (AP), osteocalcin, parathyroid hormone, vitamin D, matrix metalloproteinases MMP-1, MMP-3, MMP-8, and cartilage oligomeric matrix protein (СОМР).
Results: Psoriasis was diagnosed in 86.6% (n=52) of the patients with PA. Family history of psoriasis was confirmed in 55.0% (n=22) of the patients with psoriasis without PA and in 60.0% (n=36) of the patients with PA (p=0.681). Compared to the patients with psoriasis without PA, the patients with PA had higher prevalence of psoriatic onychodystrophy (71.6%, n=43, vs. 35.0%, n=14, p=0.0004), dactylitis (28.3%, n=17, vs. 5.0%, n=2, p=0.004), extra-articular bone proliferation signs (26.6%, n=16, vs. 5.0%, n=2, p=0.006). In the patients with PA, compared to those without PA, there was a significant increase in CRPlevels (27.4 vs. 9.5 mg/l, p=0.002), more than 2-fold increase in IgM and IgG (IgM, 2.35 vs. 1.2 g/l, p=0.023; IgG, 17.7 vs. 8.45 g/l, p< 0.0001), and CIC (89.3 vs. 29.5 mU/ml, p=0.0003). Serum phosphorus and magnesium levels in the patients with PA were lower than in the psoriasis patients without PA (phosphorus 0.8 vs. 1.6 mmol/l, respectively, p=0.045, magnesium 0.5 vs. 1.0 mmol/l, respectively, p=0.001), with somewhat higher parathyroid hormone levels (67.3 vs. 25.1 ng/ml, respectively, p=0.013). Osteocalcin levels in the PA patients were by 37.3% lower than in the patients with psoriasis without PA (17.57 vs. 24.13 ng/ml, respectively, p=0.004). MMP-1 levels in the PA groupwere 12.3-fold higher than in the non-PA group(37.68 vs. 3.05 ng/ml, respectively, p< 0.0001), and MMP-3 levels were 3.7-fold higher (42.35 vs. 11.36 ng/ml, respectively, p=0.022). In the patients with PA, APlevels were 2.52-fold higher than in the control group(150.2 vs. 59.5 U/ml, respectively, p=0.007), and COMPlevels were 2.08-fold higher (415.2 vs. 199.5 ng/ml, respectively, p=0.006).
Conclusion: The patients with PA have higher serum CRP, IgM, IgG, CIC, MMP-1, MMP-3, AP, and COMPlevels and lower osteocalcin, phosphorus, and magnesium concentrations, than the patients with psoriasis. These parameters are not PA-specific; however, the search for the most sensitive biomarkers of the systemic immune response and bone remodeling seems to be a promising area of research, since identification of such markers would allow for timely prediction and detection of PA in patients with psoriasis.
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Antitumor efficacy of an isolated hind legperfusion with a pH-increased solution in thePliss’ lymphosarcoma graft rat model
Abstract
Background: The technique of regional isolated perfusion makes it possible to increase local levels of an anti-tumor agent, to perform the treatment procedure under hypothermia or hyperthermia, to reduce or even eliminate any systemic effect of a cytostatic on the patient. In this context, the use of isolated perfusion to modify the pH milieu of the tumor seems to be a promising strategy that could potentially ensure the anti-tumor effect.
Aim: To evaluate the efficacy of a rat limb perfusion with 4% NaHCO3 solution in vivo in the Pliss' lymphosarcoma rat graft model.
Materials and methods: The experiment was carried out in Wistar rats with Pliss' lymphosarcoma graft. The isolated limb was perfused with an isotonic sodium chloride solution (the control group) or a 4% sodium bicarbonate solution (the treatment group). The following parameters were assessed: tumor node growth over time, survival rate, hematology analysis at various time points of the experiment, and histological examination of autopsy samples from the tumor.
Results: Median survival in the group perfused with 4% NaHCO3 (N = 6) was 17.2 days, whereas in the non-perfused group (the pathogenesis group) (N = 4) and in the group perfused with isotonic saline (N = 5) they were 13.2 and 13.6 days, respectively. The risk of death in the treatment group was lower compared to that in the control group (Cox regression model, hazard ratio 0.129; 95% confidence interval 0.028–0.583; p = 0.0079). There were no significant differences in the tumor growth rate over time in the perfused groups.
Conclusion: A single exposure of the tumor micro-milieu in the model with isolated perfusion of the limb with Pliss' lymphosarcoma graft does not lead to any changes in the tumor growth kinetics, but is associated with a change in the animal survival.
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CLINICAL CASES
Changes in the clinical course of psoriasis post-COVID-19: a clinical case series
Abstract
During COVID-19 pandemic, researchers and clinicians worldwide have noted changes in the course of chronic disorders of various organs and systems, which are likely to be related to systemic effects of the pathogen. Specific heterogeneous skin lesions have been identified in SARS-CoV-2 infection, including those in the patients without any history of skin disorders and exacerbation of chronic dermatoses and/or changes in their clinical manifestation. Post-COVID-19 manifestation and exacerbation of psoriasis have been also described in the literature.
We retrospectively analyzed medical files of 22 in-patients with exacerbation of psoriasis after mild or moderate SARS-CoV-2 infection in the Department of Dermatovenereology from April 2020 to April 2021. There were 7 male patients aged 42 to 74 (mean±SD 57.7±14.1) years and 15 female patients aged 40 to 78 (59.2±10.3) years. The duration of psoriasis ranged from 1 to 15 (8.7±4.7) years. Their mean PASI before the coronavirus infection had been 10.2±5.2. In the majority of the patients the psoriasis exacerbation after COVID-19 was associated with a significant increase of PASI to 18.59±4.82 (n=12, p< 0.05), 32.22±1.71 (n=5, p< 0.01), and to 59±6 (n=2, p< 0.01). In 3 patients, in addition to the increase of the rash area (PASI 10 to 17, mean 13.4±2.63), psoriatic arthritis was newly diagnosed after COVID-19.
We present a clinical case of a 33-year old male patient with a 15-year history of psoriasis, dramatic worsening of his benign psoriasis vulgaris with its transformation to the Zumbusch type of generalized pustular psoriasis after SARS-CoV-2 infection and rapid clinical improvement after the initiation of treatment with an interleukin-17A inhibitor secukinumab.
This clinical case series may contribute to the knowledge on the new coronavirus infection and its effects on the course of psoriasis.
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Adult-onset of Langerhans cell histiocytosis: a clinical case
Abstract
Langerhans cell histiocytosis is mainly diagnosed in children, and its manifestation in adult age is quite uncommon. Skin rashes may be non-specific and mimic a number of dermatoses. Therefore, the clinical diagnosis is challenging and as a rule, such patients are misinterpreted and managed for other disorders by a dermatologist for some years.
We present a clinical case of Langerhans cell histiocytosis with skin involvement in a 35-year female patient, who had been treated by a dermatologist for 2 years for pyoderma, seborrheic dermatitis, and skin fold candidiasis. Taking into account the clinical signs and symptoms and age of manifestation, we initially suspected familial benign pemphigus (Hailey-Hailey disease) or follicular dyskeratosis (Darier's disease). However, the histological assessment showed Langerhans cell histiocytosis confirmed by immunohistochemistry with anti-langerin, anti-CD1a, and anti-protein S-100 antibodies. The patient was referred to a hematologist for further work-upand specific treatment.
In cases of any treatment resistant disorders, which do not respond to long-term conventional treatment, it is necessary to reconsider the diagnosis by means of histological investigation. It would allow for identification of a disease, which is uncommon in dermatology practice.
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A clinical case of Barraquer-Simons syndrome
Abstract
Barraquer-Simons syndrome (SBS) belongs to the groupof lipodystrophy with complex etiology and pathophysiology and is characterized by progressive loss of subcutaneous fat, presumably related to autoimmune destruction of adipocytes. SBS is frequently associated with autoimmune disorders. Its first signs are found in childhood or puberty. It is characterized by gradual onset from the face with subsequent extension of the pathological process downwards without the involvement of the lower extremities. At the same time, there is a clear delimitation between the lipodystrophic and unaffected zones. The diagnosis of SBS is mainly based on clinical manifestations. Laboratory work-upis needed mostly to clarify any concomitant disorders.
We describe a rare clinical case of the Barraquer-Simons syndrome in a 61-year-old woman, associated with chronic glomerulonephritis and C3-hypocomplementemia. The disease manifested at the age of 11 years with the fat loss in the face area. No familial history of SBS could be identified. Among the concomitant diseases, chronic glomerulonephritis and bilateral retinal angiopathy are of particular interest. The laboratory assessments showed proteinuria and microhematuria in the urine analysis and decreased C3 component of the complement in blood chemistry analysis. The skin pathology was represented by atrophy of the skin and soft tissues in the face, neck, upper limbs and trunk areas, with a clear delimitation in the upper third of the thighs, where normal subcutaneous fat was preserved. There was pronounced skin hypotrophy in the face area, with face disfiguration resembling a "dead man's face". To diagnose the Barraquer-Simons syndrome, in addition to the assessment of clinical manifestations, we used non-invasive diagnostic methods and the results of histological examination of a skin biopsy samples (the description of the specimen is given).
Patients with SBS should be followed upwith the monitoring of their clinical and biochemical profiles and need an in-depth comprehensive examination by medical specialists to identify and treat their concomitant disorders.
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A clinical case of familial enteropathic acrodermatitis caused by a new genetic mutation in exon 10 of the SLC39A4 gene
Abstract
Enteropathic acrodermatitis is a rare form of genodermatoses, a group of hereditary disorders with prevailing skin lesions. The disease manifestation in children is associated with withdrawal of breastfeeding and switch to the cow milk-based products, which makes it difficult to differentiate enteropathic acrodermatitis from allergic dermatoses. We describe a familial case of enteropathic acrodermatitis in a 4-month old girl with advanced skin lesions and diarrhea. The familial history positive for enteropathic dermatitis made it possible to immediately suspect this diagnosis in the patient and to administer a zinc sulfate-containing agent before the genetic test results have become available. The response to therapy was obtained within a few days. Genetic testing of the patient identified a new mutation in exon 10 of the SLC39A4 gene. Proper collection of the past history and physician's vigilance to zinc-deficient conditions in acral dermatitis combined with alopecia and diarrhea in infants would allow for a timely and proper diagnosis and choice of a subsequent management strategy.
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