Vol 27, No 4 (2024)

BACKGROUND: Globally, colorectal cancer is the third most diagnosed cancer with an increased incidence of 1.93 million cases in 2020 according to World Health Organization. Approximately one quarter of the initial manifestations of colorectal cancer are metastatic, and 40–50% of individuals with early-stage disease eventually develop metastatic colorectal cancer (mCRC). Targeted drugs, which include epidermal growth factor receptor inhibitors (EGFRi), are a frequent choice in the therapy of metastatic colorectal cancer. Clinical observations and in vivo studies have established a significant association between the administration of EGFRi drugs and skin inflammation, particularly acute in the first 3 months. However, the role of proinflammatory cytokines in the formation of severe skin lesions has not been definitively studied. Here we present clinical evidence of the involvement of a few cytokines in the formation of the pathologic cascade of reactions during EGFR blockade on keratinocyte membranes.

AIM: Evaluation of changes in cytokine profile parameters based on the MILLIPLEX Analyte MAP panel to identify predictors of the severity of unwanted skin toxicity associated with epidermal growth factor receptor inhibition.

MATERIALS AND METHODS: Blood serum samples from 81 patients aged 18–80 years who were taking EGFRi for oncologic disease and had adverse dermatologic reactions of severity 2 or more were analyzed. The data were analyzed using SPSS software and R 4.3.1 programming language and tidyverse, rstatix packages. Detected changes with p <0.05 were analyzed considering subgroup analysis on the basis of selected cutaneous toxicity severity degrees based on the criteria developed by the US National Cancer Institute NCI-CTC v. 4.

RESULTS: Blocking of EGF receptor inhibits the expression and release of vascular endothelial growth factor (VEGF), which is the main inducer of vascular proliferation, the consequence of which is inflammation of vascular endothelium of skin capillaries. Significant increase of IFN-γ and decrease of IFN-α2 level was found in patients with manifestations of skin toxicity of 2 and more severity degree. Also, a significant criterion of severity of the skin process was an increase in the level of TNF-α. At such dissociation there is induction of STING protein (interferon gene stimulator) and increase of TNF-β production that, in its turn, leads to increase of concentration of proinflammatory cytokines G-CSF, GM-CSF, IFN-α2, IFN-γ, IL-15, IL-17A, IL-1β, IL-3, IL-6, IL-8, IP-10, TNF-α, TGF-α, IL-9. This contributes not only to the maintenance of tissue inflammation, but also to the formation of a vicious circle leading to an increase in the severity of class-mediated inflammatory response against the background of further EGFRi administration.

CONCLUSION: Determination of predictors of severity of adverse dermatologic reactions is extremely important for predicting the development of severity and further personalized tactics for correction of adverse events.

To date, the most studied clinical and morphological changes characteristic of SARS-CoV-2 virus are its pulmonary manifestations and cardiovascular involvement. However, the evaluation of COVID-associated skin changes and the analysis of their mechanisms are also important for us, because the skin manifestations of the infection can change the patient's appearance for the worse, i.e. affect the aesthetic sphere and significantly reduce the quality of life. The study of not only skin manifestations of COVID-19, but also their morphological substrate and pathogenetic basis allows us to apply the most effective methods of treatment and provide adequate management of patients even in the post-coital status.

According to the information collected to date, the most frequently reported skin manifestations of SARS-CoV-2 are pseudo-frostbite, maculopapular and vesicular lesions, urticaria, lividoid and necrotic lesions, hemorrhagic purpura (vasculitis), and conditions from the group of other unclassified skin lesions. Despite the variety of clinical variants of SARS-CoV-2-associated skin changes, morphological stigmas are often stencil-like: these are areas of lymphohistiocytic infiltration of perivascular localization, the presence of fibrinoid necrosis foci in the vessel walls, the formation of occlusive thrombi, erythrocyte extravasation. Mechanisms of damage to epidermis and dermis within COVID-19 infection may be due to the influence of complement components, activation of cytotoxic lymphocytes and NK-cells, excessive synthesis of proinflammatory cytokines, in particular, interleukin 6, as well as interferons, hyperergic reactions. In addition to routine morphological, immunohistochemical examination of skin biopsy specimens from patients with different forms of skin manifestations of SARS-CoV-2 infection is an important tool in the diagnostic confirmation of COVID-associated dermatologic pathology, especially in patients with a suspected history of this disease or with problematic laboratory results.

BACKGROUND: Seborrhea is a common problem affecting about 25% of the population. Seborrheic alopecia and seborrheic dermatitis have a negative impact on the quality of life of patients, reducing their self-esteem and social activity. However, the mechanisms underlying these diseases remain poorly understood to this day, which makes it difficult to develop effective treatments for these conditions.

AIM: To study the effect of high concentrations of blood bilirubin on the epidermis and dermis in seborrheic dermatitis and seborrheic alopecia.

MATERIALS AND METHODS: Seborrheic dermatitis of the scalp was registered in 61 patients, seborrheic alopecia ― in 23. After determining the concentration of bilirubin in the blood (total and direct), formed a group of 16 patients with seborrheic dermatitis (10 people with reference values of total and direct bilirubin and 6 people with hyperbilirubinemia), as well 23 patients as with seborrheic alopecia (9 people with reference values of total and direct bilirubin and 14 people with hyperbilirubinemia) were formed, who A histological examination of the biopsy of the skin of the affected area of the scalp was performed.

RESULTS: The formation of a thinner epidermis in seborrheic dermatitis and seborrheic alopecia at high concentrations of bilirubin is associated with the presence of a thinner spiny layer. In conditions of hyperbilirubinemia, pathological changes in the dermis are more associated with the presence of lymphohistiocytic infiltrates and the development of sclerotic changes, especially in seborrheic alopecia.

CONCLUSION: Seborrheic dermatitis and seborrheic alopecia against the background of hyperbilirubinemia is a tendency to decrease the thickness of the spiny layer, which affects the thickness of the entire epidermis. The decrease in the thickness of the stratum corneum with an increase in the granular layer, observed in seborrheic dermatitis, is a feature that is not observed in seborrheic alopecia. Manifestations of seborrheic alopecia are manifested by the presence of lymphohistiocytic infiltrates and sclerosis.

Gangrenous pyoderma is an autoinflammatory polygenic neutrophilic dermatosis characterized by the formation of painful ulcerative skin defects with boldly raised undercut edges of purplish-cyanotic coloration and an erythema zone around the focus.

Gangrenous pyoderma can manifest as an isolated dermatosis, and be associated with various autoinflammatory syndromes: PASH (gangrenous pyoderma, conglobate acne and purulent hydradenitis), PAPA (gangrenous pyoderma, pyogenic arthritis and conglobate acne), PAPASH (gangrenous pyoderma, pyogenic arthritis, conglobate acne and purulent hydradenitis), PAPASC (gangrenous pyoderma, pyogenic arthritis, conglobate acne, purulent hydradenitis and ulcerative colitis), etc.

A number of genetic mutations have been found in the syndromic forms of gangrenous pyoderma (MEFV, NOD2, LPIN2, NLRP3, NLRP12, PSMB8, MVK, IL1RN, PSTPIP1) affecting inflammatory regulatory proteins, which contributes to the development of an autoaggressive process. Neutrophilic autoinflammatory syndromes have a common pathogenesis mechanism, which is an excessive activation of the innate link of the immune system, with hyperproduction of proinflammatory IL-1, IL-17 and chemokines, leading to aseptic neutrophilic inflammation of the skin.

At the moment, the treatment of syndromic conditions remains a difficult task. Systemic glucocorticosteroids, immunosuppressants, antimetabolites, and sulfone preparations are used in complex therapy, however, more and more studies indicate the possibility of therapy with genetically engineered biological drugs with TNF inhibitors, IL-1 and IL-17.

We present two clinical observations of rare forms of autoinflammatory neutrophilic syndromic conditions PASH and PAPASC in patients aged 20 and 21 years.

According to statistics, tinea capitis remains the main mycological problem in childhood. The spectrum of causative agents of tinea capitis varies depending on the continent. In epidemiological terms, the pathogenic fungus Microsporum canis (felineum)absolutely predominates on the Eurasian continent.

A significant problem in the diagnosis and, in particular, in the treatment of microsporia are cases of the disease in very young children: we estimate this most problematic age from 1 to 18 months. Microsporia in children under the age of 1 year is the most relevant in pediatric clinical mycology due to the limited arsenal of topical and systemic medications approved at this age.

The clinical case presented in this article demonstrates an example of successful treatment of scalp microsporia in a 7-month-old child who had contraindications to systemic therapy. It should be noted that the duration of treatment in this case was almost 4 months, while the most effective therapy regimens, including systemic drugs, lead to the elimination of pathogenic fungus from the foci on the scalp within 30–45 days.

On April 16^th we held our last meeting of A.I. Pospelov Moscow Society of Dermatologists and Cosmetologists in person.

There were 102 participants and 5 applicants.

Our agenda included two clinical cases: the first one was a clinical case of fulminant acne (Miderm Clinic); the second one was about gangrenous pyoderma as a possible marker or paraneoplasia in intestinal oncological diseases (Sechenov University). We present clinical cases of patients with fulminant acne and periorbital oedema in the first report, and ascending colon tumour and T3N0M0 rectal cancer in the second report.

Three reports were presented in the scientific part of the meeting: the effectiveness of therapy for severe psoriasis (Sechenov University), the effectiveness of Janus kinase inhibitors in atopic dermatitis (Sechenov University), the molecular genetic aspects of the fungal mycosis pathogenesis (State Scientific Center of Dermatovenerology and Cosmetology). The authors presented the results of their own clinical studies of the effectiveness of therapy of diseases, including in the report on molecular-genetic aspects of the pathogenesis of mycosis fungoides the author assessed the changes in the expression levels of genes of the JAK-STAT signalling pathway and transcription factors both in visually unaffected skin and in the focus of clinically detectable lesions.

Malignant neoplasms constitute a group of the most important secondary diseases that develop in people infected with the human immunodeficiency virus (HIV). The first neoplastic disease described in HIV-infected patients is Kaposi's sarcoma. In contrast to other types of Kaposi's sarcoma, its epidemic (AIDS-associated) type is more common in young and middle-aged HIV-positive individuals, especially among men who have same-sex sex. Epidemic Kaposi's sarcoma does not have a favourite localisation. However, there is a tendency to lesions of the scalp (face, ear flaps), upper extremities, anogenital area, oral mucosa. On the trunk, the pathological process spreads along the Langer lines. Skin rashes are represented by spotty, papular, nodular elements of red-brown or purple colour. The aggressive course is characteristic: rapid dissemination and generalisation of rashes.

Plasmoblastic lymphoma is associated with immunodeficiency states and is rare. The tumour lesion is usually located in the oral cavity. Few cases of plasmoblastic lymphoma with skin and soft tissue involvement have been described in the literature.

Squamous cell skin cancer in the context of HIV infection is a dangerous disease. In people living with HIV, it manifests at a significantly earlier age and is associated with a high risk of local recurrence. The extent of invasion and the likelihood of metastasis are influenced by HIV-associated immunodeficiency.

In the vast majority of cases, risk factors and clinical manifestations of basal cell skin cancer do not differ from those in immunocompetent individuals. Basal cell carcinomas rarely metastasise. Nevertheless, metastatic forms lead to unfavourable outcome.

Here is a photo gallery of cases of neoplastic skin lesions developed in HIV-positive patients.