Academic Medical Journal

EPICUTANEOUS PATCH TEST RESULTS IN CHILDREN WITH ATOPIC DERMATITIS

Anita Najdova — 2025-06-12

Atopic dermatitis (AD) is one of the most common inflammatory diseases, occurring in 20% of children and 10% of adults in highly developed countries. It is a multifactorial disease with a complex pathogenesis, where a significant role is played by the disruption of the epidermal barrier and immune dysregulation. The wide spectrum of possible clinical manifestations complicates the categorization of these patients. Allergic contact dermatitis (ACD) is not rare in patients with AD. The aim of this study was to evaluate the results of epicutaneous patch testing with a standard series of contact allergens in children with AD and suspected for ACD and to compare the results with disease activity. The study was conducted at the University Clinic for Dermatology, Skopje, in patients with AD, aged ≤18 years. The study included 12 children, 5 girls and 7 boys, aged between 2-13 years. The patch test was negative only in one patient, two patients had only 2 positive results, and 9 patients had 4 or more than 4 positive results. In our series, ACD in children with AD was very common (11 out of 12 patients). The most common allergens were cobalt chloride, potassium dichromate, and propolis 10%.

A CASE OF RECURRENT CHLAMYDIA PNEUMONIAE INDUCED HENOCH-SCHÖNLEIN PURPURA IN 8-YEAR-OLD BOY

Nevenka Adjievska — 2025-06-12

Henoch-Schönlein purpura (HSP), synonymous with the recent term immunoglobulin A vasculitis (IgAV), is an acute autoimmune IgA-mediated disorder classified under the group of small-vessel vasculitis (SVV). It clinically manifests with the pathognomonic tetrad of palpable purpura, abdominal pain, hematuria or proteinuria, and arthritis. Although the full spectrum of clinical features is not invariably present and additional clinical manifestations may be seen, cutaneous manifestations are observed in 100% of cases, thereby serving as the one most definitive diagnostic criterion.

Young children, predominantly between ages of 2 and 10, are generally affected by the disease (90% of the cases), thereby establishing it as the most common vasculitis of childhood.

We describe a case of two episodes of Chlamydia pneumoniae induced HSP in an 8-year-old boy with an acute onset of a rash and an upper respiratory tract infection preceding the onset, and with possible simultaneous multi-factorial infective etiology contributing to the severity of the disease.

Given the rarity of reported cases, only two to our knowledge, it is challenging to establish a definitive causal relationship between Chlamydia pneumoniae and HSP.

However, this uncommon association highlights the importance of considering this atypical pathogen in the etiological differential diagnosis of HSP, especially in patients presenting with preceding respiratory symptoms. Early diagnosis is crucial for preventing complications and ensuring optimal management, with prompt recognition of diverse triggers, such as infections, being essential for tailored therapy and improved patient outcomes.

GENERALIZED MORPHEA: CASE REPORT AND TREATMENT APPROACH

Nevenka Adjievska — 2025-06-12

Morphea, also known as localized scleroderma, is a rare autoimmune disorder characterized by excessive collagen deposition, leading to fibrosis of the skin. Unlike systemic scleroderma, morphea does not affect internal organs but can cause significant morbidity due to skin hardening and potential involvement of underlying tissues such as muscles and joints.

An 11-year-old female patient was hospitalized for the first time at the Dermatology Clinic due to hyperpigmented skin lesions. According to the heteroanamnesis provided by her father, the lesions initially appeared on her thighs approximately one year ago, with an estimated size of around 20 cm. She was treated on an outpatient basis by a dermatologist, though no details on the therapy were provided. One month prior to hospitalization, the lesions worsened, expanding to the lower legs, chest, and upper extremities, accompanied by itching. Dermatological assessment revealed erythematous-livid, slightly indurated patches with a shiny, smooth surface. The lesion demonstrated areas of coalescing hyperpigmentation and hypopigmentation, distributed across the chest, abdomen and extremities. A skin biopsy was performed and confirmed early inflammatory-stage morphea.

Phototherapy, particularly UVA is an effective treatment for early-stage and inflammatory morphea, helping to reduce fibrosis, restore skin flexibility, and improve pigmentation. When combined with immunosuppressive agents, it enhances clinical outcomes and slows disease progression. Early intervention, guided by a multidisciplinary team, leads to a favorable prognosis, though long-term follow-up is essential to monitor recurrence and optimize management.

ADULT-ONSET ATOPIC DERMATITIS: CLINICAL CASE ANALYSIS WITH DIAGNOSTIC AND THERAPEUTIC INSIGHTS

Ivana Dohcheva Karajovanov — 2025-06-12

Introduction: Adult-onset atopic dermatitis (AOAD) is a distinct and increasingly recognized condition. This case report presents a patient with severe AOAD, both highlighting diagnostic and therapeutic challenges. Case Report: A 43-year-old male with extensive eczema and elevated IgE levels was treated with systemic corticosteroids, antihistamines, emollients, and phototherapy. Significant clinical improvement was noted. Conclusion: This case illustrates the complex management of AOAD and emphasizes the need for a multidisciplinary and personalized treatment approach.

Objective: This paper discusses a case of AOAD, providing clinical and diagnostic insights while integrating evidence from current literature.

Methods: A 43-year-old male with severe AOAD was evaluated using the Hanifin-Rajka criteria and the SCORAD index for diagnosis and severity assessment. Laboratory, histopathological, and allergological investigations supported the diagnosis. Relevant literature was reviewed to contextualize findings.

Results: The patient presented with extensive xerosis, erythema, and pruritus. Elevated serum IgE and eosinophilia confirmed a heightened atopic state. Management included systemic corticosteroids, antihistamines, emollients, and UVA phototherapy, resulting in symptom improvement. The case highlights the systemic and relapsing nature of AOAD, requiring a multidisciplinary approach.

Conclusion: AOAD differs significantly from COAD in pathogenesis, clinical features, and management. This case contributes to the growing body of literature on AOAD by showcasing its unique clinical features and the complexities associated with managing this under-recognized condition. Personalized, targeted therapies addressing skin barrier dysfunction, immune dysregulation, and systemic inflammation are essential to optimize outcomes.

NEONATAL INCONTINENTIA PIGMENTI – A CASE REPORT

Milena Kacarska Mickoska — 2025-06-12

Incontinentia pigmenti or Bloch-Sulzberger syndrome, is a rare multisystem, X-linked dominant disorder that most commonly occurs in female newborns. It is usually lethal, and most pregnancies with male fetuses result in miscarriage or stillbirth, while in female newborns, it can appear with different severity and multiorgan symptoms, including dermatological, neurological, ophthalmological, and dental abnormalities. Skin changes usually appear immediately after birth or in the first few weeks of life, following four stages: vesicular, verrucous, hyperpigmented, and hypopigmented. In the neonatal period, IP is clinically diagnosed based on the appearance of vesicles arranged in a linear pattern following Blaschko’s lines, representing the first stage of skin involvement. The differential diagnosis of a vesicular eruption in a neonate is extensive and includes various infectious and non-infectious causes.

We report a case of a one-day-old female neonate who presented at birth with erythematous vesicles linearly distributed on the extremities, over the thorax and abdomen. Based on suspicious Blaschkoid skin lesions and eosinophilic skin infiltration in biopsy, incontinentia pigmenti was diagnosed.

Early recognition of IP is crucial for appropriate management and monitoring of potential complications, particularly those involving the central nervous system and eyes. Although there is no specific cure for IP, a multidisciplinary approach involving dermatologists, neurologists, ophthalmologists, and dentists can help optimize the quality of life of affected infants.

SPONTANEOUS IMPROVEMENT IN A PATIENT WITH JUVENILE PITYRIASIS RUBRA PILARIS

Ana Petkova — 2025-06-12

Pityriasis rubra pilaris (PRP) is a rare and complex dermatosis characterized by erythematous plaques, follicular papules, hyperkeratosis, and scaling. While its precise etiology remains largely unidentified, genetic predisposition, immune-mediated mechanisms, and environmental triggers are implicated in its pathogenesis.

We present a case of a 3-year-old child with a 1-month history of erythematous macules, initially affecting the hands, feet, perioral, and periocular regions. The lesions were initially recognized by a dermatologist and pediatrician as hand, foot, and mouth disease (HFMD). Two weeks later, the patient developed widespread involvement of 80% of the skin surface, including the face. Considering the evolutionary progression of the clinical changes, a diagnosis of pityriasis rubra pilaris (PRP) was established.

After 6 weeks of local treatment with corticosteroids and emollients, significant reduction in body surface area (BSA) was observed. The idea of initiating systemic therapy with acitretin was dismissed, given the favorable course of the disease. After 5 months of clinical observation, the patient achieved complete resolution of the skin changes, highlighting the self-limiting nature of the juvenile form. The patient underwent frequent check-ups for 1 year, and no changes or relapses were observed. This case highlights the value of conservative management and vigilant monitoring in achieving long-term resolution and minimizing the need for systemic interventions.

TWO PEDIATRIC CASES OF URTICARIA MULTIFORME

Tomche Popovski — 2025-06-12

Urticaria multiforme is a morphological subtype of acute urticaria, often mistaken for erythema multiforme, serum sickness, or cutaneous vasculitis. Synonyms include acute annular urticaria, acute urticarial hypersensitivity syndrome, echymotic urticaria, and urticaria hemorrhagica. Diagnostic criteria are typical annular and polycyclic urticaria, echymotic changes, pruritus, acral edema, and absence of target lesions, necrosis, or bullous changes. Echymotic changes last 24-48 hours, with rapid response to antihistamines and corticosteroids. It typically affects children aged 4 months to 4 years. We describe two pediatric cases with typical clinical and laboratory features of urticaria multiforme.

A 3-year-old boy was admitted with migratory, erythematous, pruritic wheals that appeared on the fourth day of fever, following antipyretic treatment. No prior medical history or recent vaccinations. By day 2, peripheral edema and diffuse erythema developed. Between days 3-5, polycyclic, ecchymotic wheals appeared along with new itchy lesions. An otherwise healthy 11-month-old girl was hospitalized with erythematous, pruritic wheals and annular, urticaroid, erythema multiforme-like lesions. Symptoms began on day 2 after a 7-day course of antibiotics for an upper respiratory infection. No prior medical history, allergies, or recent vaccinations. After corticosteroid and antihistamine treatment, the lesions resolved completely by over the course of one week in both cases.

DEMODEX-INDUCED CUTANEOUS PSEUDOLYMPHOMA

Tomche Popovski — 2025-06-12

Cutaneous Pseudolymphoma, also referred to as Lymphoid Infiltrate of the Skin, is defined as a benign, inflammatory, reversible, reactive, and polyclonal proliferation of lymphocytes that spontaneously regresses or resolves following the elimination of the triggering factor. Cutaneous pseudolymphomas represent a heterogeneous group of T-cell or B-cell lymphoproliferative disorders, which may be localized or disseminated, and which clinically and histopathologically mimic cutaneous lymphomas. The literature describes various potential etiological factors, including endogenous (genetic, immunological) and exogenous factors (insect bites, medications, vaccinations, ultrasound exposure, trauma, tattoos, acupuncture, infections, etc.).

We present the case of a 64-year-old patient with pruritic nodular lesions on the face, neck, and back, as well as chronic blepharitis, persisting for over a year despite various therapeutic approaches (topical corticosteroids, antifungals, and antibiotics). Based on clinical examination and detailed anamnesis, our differential diagnoses included follicular mucinosis, cutaneous lymphoma, sarcoidosis, and facial eosinophilic granuloma. A skin biopsy was performed (from a nodular lesion on the frontal region), revealing an increased presence of Demodex mites and histopathologically numerous mites and scattered eosinophils. Immunohistochemical analysis demonstrated an immunophenotype of CD4>CD8, CD20(+), CD60(+), Ki67, and CD137, consistent with a benign reactive process. The diagnosis of pseudolymphoma was established based on clinical presentation and histopathological evaluation. Three months of local and systemic antiparasitic therapy led to complete regression of symptoms.

MELANODERMA AS AN EARLY CLINICAL MANIFESTATION OF SÉZARY SYNDROME

Ordanche Ribarski — 2025-06-12

Primary cutaneous lymphomas are a heterogeneous group of hematologic malignancies originating from the T-cells or B-cells residing within the human skin. More than two-thirds (70-85%) of cases are diagnosed as cutaneous T-cell lymphomas (CTCL) with Mycosis fungoides and Sézary syndrome being the most notable. CTCL have an annual incidence of 10 cases per 1 million, with a predominance to males over the age of 50 (male-to-female ratio of 2:1).

Here, we present a case of a 54-year-old female who presented with persistent and generalized hyperpigmentation, later evolving into Sézary syndrome. Initially, the patient was reffered to the University Clinic for Dermatology in Skopje, due to a five-month medical history of persistent pruritus and hyperpigmentation. Based on the clinical presentation and skin biopsy findings consistant with non-specific dermatitis, she was diagnosed as having atopic dermatitis and underwent treatment with topical steroids and emollients. However, the clinical presentation got worsen in the following six months, and evolved into generalized melanodermia with ulcerated tumor growths. In order to conclude the final diagnosis, a biopsy of the skin lesions was performed with histopathological findings consistent with Sézary syndrome. Following this diagnosis, the patient was referred to the University Clinic for Hematology in Skopje for further treatment.

PELLAGRA-LIKE DERMATITIS - A CASE REPORT

Kujtime Rushiti Mehmeti — 2025-06-12

Pellagra-like dermatitis refers to a skin condition resembling the dermatologic manifestations of pellagra, which is a systemic disease resulting from niacin (vitamin B3) deficiency. Vitamin B3 is needed for several metabolic processes, cell signaling and DNA repair. This condition is characterized by a photosensitive rash that typically affects sun-exposed areas. The classic skin changes include symptoms known as the 4Ds: dermatitis, diarrhea, dementia and death. The main causes of pellagra are: nutritional deficiency of niacin, restrictive diets, chronic alcoholism, gastrointestinal malabsorption, metabolic disorders and certain medications.

We present the case of a 55-year-old farmer, with megaloblastic anemia and a seven-month history of skin changes, including erythematous lesions on sun-exposed areas such as the face, neck, bilaterally on forearms, dorsum of the hands and feet, along with itching and desquamation. Gastrointestinal symptoms included intermittent diarrhea, weight loss, neurological symptoms, and anxiety. Laboratory tests revealed anemia, hypoproteinemia, low levels of folic acid and serum iron. Skin biopsy results were consistent with pellagra, but did not exclude contact dermatitis. Treatment with niacin, folic acid, vitamin B12 and iron led to significant clinical improvement. Regular follow-up visits with hematology, gastroenterology, neurology specialists, and nutritional therapy were recommended.

While pellagra is rare in modern clinical practice due to better nutrition, it still occurs sporadically. Diagnosis relies on the classic 4D features, laboratory findings and histopathological features. Despite its rarity, pellagra-like dermatitis should be considered in differential diagnoses for dermatological and gastrointestinal symptoms. Early diagnosis and treatment can result in significant improvement.

ACUTE TELOGEN EFFLUVIUM FOLLOWING SARS-COV-2 INFECTION: A RARE PEDIATRIC CASE

Petra Temelkova — 2025-06-12

Telogen effluvium is a temporary, non-scarring form of diffuse hair loss, characterized by a shortened anagen phase and increased telogen club hair shedding. It can appear three months after a stressful event and may last up to six months. Various factors, including the SARS-CoV-2 virus seen during the COVID-19 pandemic, can contribute to the onset of telogen effluvium. The exact pathophysiological mechanism of hair loss caused by the virus remains unclear and continues to be under investigation. Telogen effluvium following COVID-19 has been frequently described in adults; however, there are few published cases in children. We present a rare case of post-COVID-19 telogen effluvium in a 6-year-old girl, one month after infection. The COVID-19 infection presented with mild fever, fatigue, sore throat, and upper respiratory symptoms, treated only with symptomatic therapy. Other causes of hair loss were ruled out. The dermatological evaluation showed diffuse hair loss on the scalp, more noticeable in the frontoparietal region, with no scarring, accompanied by a positive hair pull test. The diagnosis was made by the dermatologist based on the detailed anamnesis, complete laboratory workup with differential blood count, dermatological assessment, and a positive hair pull test. No medication was prescribed, and after 8 months, the condition improved on its own. This case highlights that post-COVID-19 telogen effluvium is rare in the pediatric population, emphasizing its psychological impact and the importance of reassuring the patient that it is a reversible, self-limiting condition.

URTICARIA PIGMENTOSA: A CASE OF PEDIATRIC RARE CUTANEOUS MACULOPAPULAR MASTOCYTOSIS

Petra Temelkova — 2025-06-12

Mastocytosis in children is a rare disorder characterized by an abnormal accumulation of mast cells in the skin and/or different organs Based on the site of mast cell accumulation, pediatric mastocytosis can be classified into two categories: cutaneous mastocytosis and systemic mastocytosis. The World Health Organization classification system differentiates three clinical variants of cutaneous mastocytosis: mastocytoma, urticaria pigmentosa also known as maculopapular cutaneous mastocytosis, and diffuse cutaneous mastocytosis. We present a clinical case of urticaria pigmentosa in an infant.

In January 2025, a five-month-old infant was referred to the University Clinic for Dermatology, due to the presence of multiple brownish macules disseminated across the trunk and upper extremities, accompanied by a mild degree of pruritus. The infant was generally healthy, born from an uncomplicated pregnancy, with no family history of dermatological diseases. The lesions were not present at birth. The first signs of pigmentation were noticed by the parents approximately three months prior, with a gradual increase in both the number and size. The dermatological status revealed the presence of more than 20 pigmented macules, each approximately 1 cm in diameter, localized on the trunk and upper extremities. A diagnosis of urticaria pigmentosa was established based on the clinical appearance and presence of positive Darier's sign, whereas a skin biopsy was unnecessary. The treatment regimen for the infant included only oral antihistamines. Long-term follow-up of this patient is needed, as the child has not yet reached puberty, in order to assess the severity and prognosis of the disease.

Letter from the Guest Editors

Katerina Damevska — 2025-06-12

GUIDELINES FOR SYSTEMIC TREATMENT OF PATIENTS WITH PSORIASIS AT THE UNIVERSITY CLINIC FOR DERMATOLOGY – SKOPJE

Tomica Sotirovski — 2025-06-12

Psoriasis is a chronic autoimmune disease that causes inflammation in your skin and encompasses several disease subtypes (plaque, inverse, guttate, pustular, erythrodermic, nail and sebopsoriasis), requiring a standardized approach to diagnosis and treatment. According to current recommendations, the treatment involves the use immunosuppressants and biologic therapy which has already been approved as a first-line treatment for moderate to severe psoriasis in Europe and USA. These guidelines are made for the needs of the University Clinic for Dermatology – Skopje and are based on the European guidelines on the systemic treatment of psoriasis (EuroGuiDerm Guidelines on the systemic treatment of Psoriasis vulgaris, 2020). They include a system for grading disease severity, and recommendations for treatment and monitoring. Systemic treatment modalities included in these guidelines are: acitretin, ciclosporin, methotrexate, adalimumab, apremilast, brodalumab, certolizumab, pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab.

GUIDELINES FOR THE SYSTEMIC TREATMENT OF PATIENTS WITH PEMPHIGUS AT THE UNIVERSITY CLINIC FOR DERMATOLOGY – SKOPJE

Julija Mitrova Telenta — 2025-06-12

Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions on the mucous membranes and skin, requiring a standardized approach to diagnosis and treatment. According to current recommendations, the treatment of diseases in this group involves the use of systemic corticosteroids in combination with immunosuppressants (azathioprine and mycophenolate mofetil), as well as biological therapy with rituximab, which has already been approved as a first-line treatment for moderate to severe pemphigus vulgaris in Europe and the USA.

These guidelines were developed for the needs of the University Clinic of Dermatology – Skopje, which serves as a referral center for the diagnosis and treatment of pemphigus in the Republic of North Macedonia. They are based on the Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the European Academy of Dermatology and Venereology (EADV). The guidelines include general information about the disease, a system for grading disease severity, and recommendations for treatment and monitoring.

GUIDELINES FOR SYSTEMIC TREATMENT OF PATIENTS WITH ATOPIC DERMATITIS AT THE UNIVERSITY CLINIC FOR DERMATOLOGY IN SKOPJE

Anita Najdova — 2025-06-12

This Guideline was developed for the needs of the University Clinic (UC) for Dermatology in Skopje and is based on the European Guidelines for the Systemic Therapy of Atopic Dermatitis (AD) from 2020 and 2021 (EuroGuiDerm Guideline). Dermatologists from the UC for Dermatology with extensive experience in pediatric dermatology and treating patients with AD participated in the process. The Guideline was adopted by the Expert Board of the UC for Dermatovenerology in Skopje in February 2025.

This part of the Guideline contains general information about the goals and scope, the health issues covered in the Guideline, the target groups, and a methodology section. The Guideline provides guidelines for identifying patients who should be treated with systemic therapy and recommendations and information for each systemic drug. In addition, the Guideline provides recommendations and information on each systemic drug. The first section describes systemic treatment options, such as conventional immunosuppressive drugs (azathioprine, cyclosporine, glucocorticosteroids, methotrexate, and mycophenolate mofetil), biologic agents (dupilumab, lebrikizumab, nemolizumab, omalizumab, and tralokinumab) and Janus kinase inhibitors (abrocitinib, baricitinib, and upadacitinib).

GUIDELINES FOR TOPICAL TREATMENT OF PATIENTS WITH ATOPIC DERMATITIS AT THE UNIVERSITY CLINIC FOR DERMATOLOGY IN SKOPJE

Anita Najdova — 2025-06-12

This Guideline was developed for the needs of the PHI University Clinic for Dermatology, Skopje, and is based on the European Guidelines for Local Therapy of Atopic Dermatitis (AD) from December 2020 and July 2021 (EuroGuiDerm Guideline). The process involved specialist physicians from the University Hospital for Dermatology with extensive experience in pediatric dermatology and the treatment of patients with atopic dermatitis (AD), as well as resident physicians involved in the technical preparation of the text. The Professional Board of the University Clinic for Dermatology in Skopje adopted the Guideline in February 2025. The first part of the Guideline contains general information about the goals and scope, the health issues covered in the Guideline, the target groups, and a methodology section. The Guideline provides guidelines for identifying patients who should be treated with topical therapy, recommendations, and information for each drug and emollient. This Guideline includes recommendations and information on essential therapy with emollients and moisturizers, topical anti-inflammatory, antimicrobial, and antipruritic treatment, UV phototherapy, techniques for avoiding provocative factors, and recommendations for nutrition, complementary medicine, and education for patients with AD.

CHEMICAL VITILIGO: A LITERATURE REVIEW

Katerina Damevska — 2025-06-12

Chemical vitiligo is an underdiagnosed form of skin depigmentation caused by repeated chemical agent exposure, affecting both adults and children. Chemical vitiligo is also called chemical leucoderma, contact vitiligo, and/or occupational vitiligo. Most of the implicated chemical agents are derivates of phenol and catechol, which have melanotoxic effects in individuals with genetic susceptibility. The diagnosis of chemical vitiligo is based on the medical history and patch testing, as histopathology is usually inconclusive and cannot differentiate chemical from idiopathic vitiligo. Patients typically report multiple exposures to specific melanotoxic or depigmenting chemical substances, either in the household or at the workplace, followed by the appearance of diffuse confetti-like and/or pea-sized hypopigmented macules, usually on the face, hands, and feet. The widespread distribution of hypopigmented macules is often the result of sensitization, autotransfer, or heterotransfer of the chemical agent from the primary site of contact. Later, the clinical suspicion of chemical vitiligo can be confirmed with the patch test. Once the diagnosis is established, the patient should be advised to avoid the incriminated chemical agent. In some cases, when spontaneous repigmentation does not occur, additional treatments are recommended, such as ultraviolet B phototherapy, photochemotherapy, and topical immunosuppressants.

VITILIGO: WHAT’S OLD, WHAT’S NEW?

Maja Dimova — 2025-06-12

Vitiligo is a chronic, inflammatory, autoimmune disorder resulting from a selective destruction of melanocytes and the appearance of depigmented skin patches. It affects all ethnic groups and genders equally, with a slight female predominance. It is estimated that approximately 0.5-2% of the global population suffer from vitiligo, making this dermatosis the most common pigmentation disorder. Vitiligo is a complex disease with complex etiology and pathogenesis. It is currently accepted that genetic predisposition and environmental factors lead to melanocyte oxidative stress, and activation of abnormal immune response, but the overall contribution of each of these processes remains insufficiently clear.

Historically, vitiligo was recognized in ancient times, with evidence found in ancient Egyptian, Greek, and Indian texts. Early interpretations associated this skin disease with divine punishment or contagion, leading to quarantines and stigmatization. Today, vitiligo is classified as an autoimmune disease, with autoimmune attack on melanocytes considered the primary factor leading to the appearance of depigmented macules. The skin and gut microbiome and neural hypothesis have recently gained attention as emerging factors in the pathogenesis of vitiligo.

The treatment of vitiligo remains a significant challenge. It includes local and systemic immunosuppressives, phototherapy, surgical techniques, as well as other therapeutic approaches, including traditional medicine, camouflage, depigmentation, and psychological interventions. However, vitiligo has a long treatment cycle, and all current treatments provide only short-term benefits, with relapse of the disease being common once treatments are discontinued. In recent years targeted therapies such as JAK inhibitors are actively being developed.

THERAPEUTIC EFFECT OF CANNABIDIOL (CBD) IN PLAQUE PSORIASIS

Dejan Filipovik — 2025-06-12

The endocannabinoid system (ECS) of the skin is a complex molecular network of receptors, endocannabinoids, and enzymes that has sparked the interest of modern dermatology since its discovery in 1988. Studies have shown that dysregulation of ECS is closely associated with various skin diseases, including psoriasis as one of the most common autoimmune skin diseases. Psoriasis has a bimodal distribution of onset and a massive socioeconomic impact in modern societies, since it affects 3% of the global population. Although our knowledge regarding the association between ECS and psoriasis is limited, modulators of ECS have paved a novel therapeutic approach to be considered when treating psoriasis patients. Cannabidiol (CBD) is a non-psychotic, lipophilic, twenty-one carbon terpenophenolic phytocannabinoid derived from Cannabis plant that has promising therapeutic properties. Topical or transdermal formulations containing CBD have anti-inflammatory properties via inhibition of NF-kB signaling pathway and upregulation of keratin 6 and 16 in psoriasis patients. This review article discusses the up-to-date knowledge of the endocannabinoid system in the skin, its role in the pathophysiology of psoriasis, and therapeutic potential of cannabidiol in treatment of patients with plaque psoriasis.

THE IMPACT OF HOMOCYSTEINE IN LUPUS ERYTHEMATOSUS: A LINK OF INFLAMMATION, SKIN AND CARDIOVASCULAR RISK

Nora Pollozhani — 2025-06-12

Lupus erythematosus (LE) is a complex autoimmune disease with diverse clinical manifestations, ranging from systemic involvement to cutaneous lesions. Cutaneous lupus erythematosus (CLE) is the second most common manifestation of LE, resulting in disfiguring scaring, hair loss and significant burden for the patients’ quality of life.

Elevated homocysteine (Hcy) levels, or hyperhomocysteinemia (HHcy), are observed in both SLE and CLE. Hcy contributes to endothelial dysfunction, thrombosis risk, and immune activation through pro-inflammatory cytokine release, oxidative stress, and vascular damage. Additionally, it disrupts T-cell function and epigenetic regulation, further exacerbating autoimmune responses.

Several factors can cause HHcy, including genetics (such as MTHFR mutations), kidney problems, metabolic disorders, certain medications, and deficiencies in B vitamins (B6, B9, B12). Since B vitamins help regulate Hcy, a poor diet or an inability to properly absorb nutrients may contribute to higher Hcy levels in lupus patients. Additionally, HHcy is a recognized risk factor for cardiovascular disease (CVD), a major cause of morbidity in lupus patients. Increased Hcy levels contribute to arterial stiffness, endothelial injury, and thrombotic complications, elevating the risk of atherosclerosis, stroke, and myocardial infarction.

Hcy may act as a biomarker for disease severity and vascular risk in CLE. Interventions such as B-vitamin supplementation and lifestyle changes could offer therapeutic benefits. However, further research is needed to clarify its role in CLE pathogenesis and its potential for clinical management.

DISRUPTION OF HAIR FOLLICLE IMMUNE PRIVILEGE IN ALOPECIA AREATA: ENIGMATIC MECHANISMS AND EMERGING CONCEPTS

Viktor Simeonovski — 2025-06-12

Immune privilege (IP) is a specialized immunological state that protects certain tissues, including the hair follicle (HF), from immune-mediated destruction. The maintenance of hair follicle immune privilege (HFIP) is crucial for uninterrupted hair growth and is mediated by several mechanisms. These include the downregulation of major histocompatibility complex (MHC) class I molecules, the secretion of immunosuppressive cytokines such as transforming growth factor-beta (TGF-β) and alpha-melanocyte-stimulating hormone (α-MSH), and the recruitment of regulatory immune cells that suppress pro-inflammatory responses.

Additionally, the blood-hair follicle barrier limits immune cell infiltration, further preserving immune privilege. However, in alopecia areata (AA), HFIP collapses triggering an autoimmune attack against follicular structures. This breakdown is marked by increased antigen presentation, heightened expression of MHC class I and II molecules, and an influx of autoreactive cytotoxic CD8+ T cells. These T cells, particularly those expressing the NKG2D receptor, recognize stress-induced ligands on follicular keratinocytes and initiate a cytotoxic response. Interferon-gamma (IFN-γ) and interleukin-15 (IL-15) play central roles in amplifying inflammation by activating the JAK-STAT signaling pathway, further promoting immune cell infiltration and follicular destruction. Additional immune cells, including natural killer cells, dendritic cells, and macrophages, contribute to disease pathogenesis by enhancing antigen presentation and sustaining the inflammatory cascade.

Given the central role of HFIP collapse in AA, therapeutic strategies aimed at restoring immune privilege represent a promising avenue for long-term disease management. Future research should focus on identifying key molecular regulators of HFIP and developing targeted interventions to re-establish immune tolerance within the hair follicle.

THE WAR UNDER THE SKIN - BIOFILM AND INFLAMMATION IN CHRONIC WOUNDS

Julija Mitrova Telenta — 2025-06-12

The skin, the largest organ in the body, protects against external stimuli and microorganisms. A balanced skin microbiota, including both commensal and pathogenic microorganisms, is essential for skin health. Disruptions in this balance can lead to infections and inflammation, which are key factors in delayed wound healing. Biofilm formation further complicates the process. In chronic wounds, healing is often impaired during the inflammatory phase due to persistent activation of the immune response. This leads to increased immune cell activation, along with heightened activity of matrix metalloproteinases (MMPs), collagenase, and elastase, while tissue inhibitors of matrix metalloproteinases (TIMPs) decrease. Host factors such as wound depth, duration, local hypoxia, and immune responses contribute to healing delays. Microbial factors, including bacterial diversity, microbial load, and pathogenicity, also play a significant role. Biofilms are more resistant to antimicrobial therapy than free-floating bacteria. Its formation in chronic wounds triggers sustained inflammation, marked by elevated inflammatory mediators like IL-6, IL-10, IL-17A, and TNF-α. Biofilms not only prolong inflammation but also cause oxidative stress and protease-mediated degradation of essential receptors and cytokines, accelerating wound bed senescence. The presence and persistence of biofilm in chronic wounds affect the host’s immune response. Understanding this relationship offers more opportunities for successful treatment.

NEONATAL LUPUS SYNDROME – AN OVERVIEW OF THE PATHOGENESIS, CLINICAL FEATURES, AND MANAGEMENT APPROACH

Nikolina Zdraveska — 2025-06-12

Neonatal lupus erythematosus (NLE) is a rare immune-mediated condition that affects newborns due to the transplacental transfer of maternal antibodies, specifically anti-Ro/SSA and/or anti-La/SSB. Seropositive mothers may have known or undiagnosed autoimmune diseases, and many of them remain asymptomatic.

NLE is associated with various phenotypic characteristics and can affect multiple organ systems, including the skin, heart, blood, and liver. The most severe manifestation of NLE is a complete atrioventricular block, which may occur in utero and is irreversible. Cutaneous manifestations resemble the rash seen in subacute lupus erythematosus and are generally benign and self-limiting, typically resolving completely within four to six months.

During the neonatal period, these rashes are frequently misdiagnosed and confused with other common erythematous conditions, particularly when the mother is asymptomatic.

Although NLE typically has a benign course, its clinical significance is highlighted by a tenfold increased risk of recurrence in subsequent pregnancies, as well as its association with more severe clinical outcomes. This article provides a comprehensive review of pathogenesis, clinical manifestations and management of NLE aiming to serve as a valuable reference for clinical practitioners in the field.

CHRONIC INFLAMMATION IN DIALYSIS PATIENTS AND ITS CORRELATION WITH DERMATOLOGICAL MANIFESTATIONS: A MULTICENTER STUDY FROM SKOPJE

Ivana Dohcheva Karajovanov — 2025-06-12

Introduction: Chronic systemic inflammation is a defining feature in dialysis patients, contributing significantly to dermatological manifestations such as pruritus, xerosis, pigmentation changes, and nail abnormalities. These conditions impair quality of life and are linked to markers of systemic inflammation and dialysis-related factors.

Objectives: This study aimed to analyze the prevalence and severity of dermatological manifestations in dialysis patients, and their correlations with systemic inflammation.

Methods: An observational, cross-sectional study was conducted in two dialysis centers in Skopje, North Macedonia, involving 167 chronic dialysis patients. Data collection included dermatological assessments, laboratory markers (e.g., CRP, PTH, MPV), and pharmacological histories. Statistical analyses were used to explore correlations.

Results: Pruritus was observed in 74% of patients and correlated significantly with CRP (R=0.223, p=0.005) and PTH (R=0.219, p=0.008). Xerosis affected 88.62% of patients, with moderate severity in 38.92%, and correlated with CRP (R=0.215, p=0.003). Pigmentation changes (63.47%) were linked to MPV (R=0.219, p=0.004), while nail abnormalities (81.44%) correlated with ferritin (R=0.170, p=0.028).

Conclusion: Dermatological manifestations are prevalent in dialysis patients and closely associated with systemic inflammation markers. A multidisciplinary approach is essential to improve management and patient outcomes.