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Methotrexate is an immunosuppressive drug with remarkable therapeutic results in the treatment of autoimmune and proliferative skin diseases. Although it has been more than half a century since it was first introduced into the therapeutic arsenal of dermatologists, there are currently no standardized therapeutic protocols regarding the prescription of methotrexate in dermatology, with the exception of psoriasis treatment. This review aims to highlight the indications and benefits of methotrexate beyond psoriasis, with a focus on a wide range of inflammatory, vesiculobullous, and proliferative dermatological pathologies.
Assuntos
Imunossupressores , Metotrexato , Psoríase , Dermatopatias , Humanos , Metotrexato/uso terapêutico , Dermatopatias/tratamento farmacológico , Imunossupressores/uso terapêutico , Psoríase/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Fármacos Dermatológicos/farmacologiaRESUMO
Infectious and inflammatory dermatoses featuring skin lesions with loss of tissue expose skin layers to microbial invasions, disrupt the normal skin microbiome, and potentially lead to sepsis. However, literature data on the incidence of cutaneous-onset sepsis are scarce. This retrospective observational study assessed hospital admissions for primary skin lesions without bacterial infections and sepsis during 2020-2022 in the largest emergency hospital in NE Romania. Of 509 patients, 441 had infected lesions, 78 had sepsis caused by venous ulcers from microbial eczema cellulitis, superinfected bullous dermatoses, erysipelas, and erythroderma. Cultured samples revealed S. aureus, P. aeruginosa, and E. coli; and K. pneumoniae and S. ß-hemolytic associated with sepsis, even if this was rarer. Clinical manifestations included ulcerations, erosions, fissures, excoriations, bullae, vesicles, pruritus, tumefaction, edema, fever, chills, pain, adenopathy, and mildly altered mental status. Underlying chronic heart failure, atrial fibrillation, anemia, and type-1 diabetes mellitus were comorbidities associated with infection and sepsis. Significant associations and risk factors, including their combined effects, are discussed to draw attention to the need for further research and adequate management to prevent sepsis in adult patients of any age presenting with infected skin lesions (especially cellulitis) and comorbidities (especially type 1 diabetes mellitus and anemia).
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Psoriasis is a chronic inflammatory skin condition, with genetic, epigenetic, environmental, and lifestyle factors contributing to its onset and recurrence. Severe psoriasis has a great impact on quality of life, which is similar to that of insulin-dependent diabetes, depression, and ischemic heart disease, but with a lower mortality. There is an overlap between the rising incidences of autoimmune diseases and obesity. In recent years, research has shown that there is an association between psoriasis and obesity. Psoriasis is linked to obesity in a two-way manner, as each can precipitate the development of the other. Several adipose tissue-secreted adipokines were shown to be elevated in obese psoriasis patients, exhibiting similar mechanisms of action to those underlying the pathogenesis of psoriasis. Excess body weight can influence not only the treatment response in psoriasis, but also the adverse events, leading to decreased patient compliance. Specific human microbiome patterns have been identified for obesity and psoriasis and could represent a future therapeutic target in selected individuals.
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The European Society for Medical Oncology experts have identified the main components of the long-term management of oncological patients. These include early diagnosis through population screening and periodic control of already diagnosed patients to identify relapses, recurrences, and other associated neoplasms. There are no generally accepted international guidelines for the long-term monitoring of patients with skin neoplasms (nonmelanoma skin cancer, malignant melanoma, precancerous-high-risk skin lesions). Still, depending on the experience of the attending physician and based on the data from the literature, one can establish monitoring intervals to supervise these high-risk population groups, educate the patient and monitor the general population.
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BACKGROUND: Autoimmune bullous diseases (ABDs) are a rare but significant group of dermatoses that pose great challenges to the treating dermatologist. ABDs are characterized by the presence of tissue-bound and circulating autoantibodies directed against disease-specific target antigens of the skin. Most epidemiological studies have focused on a single ABD. More than that, there are few data about the incidence and prevalence of autoimmune blistering diseases in Romania. METHODS: In this study, between 2015 and 2019, we retrospectively investigated a total of 225 patients with autoimmune bullous diseases from the northeastern region of Romania. The diagnosis was based on the clinical and histo- and immunohistological findings. RESULTS: Pemphigus was the most frequently encountered ABD, with an incidence of 8.16/1,000,000 inhabitants, representing 58.7% (132 cases), followed by 24% cases of bullous pemphigoid (54 cases), 15.4% of patients were diagnosed with dermatitis herpetiformis (37 cases), and 0.9% other subepidermal autoimmune bullous dermatoses. The average age of onset of pemphigus vulgaris was 59.4 years, the majority of patients being male, while the average age of patients diagnosed with bullous pemphigoid was 73.8 years, the majority being female. CONCLUSIONS: Pemphigus vulgaris is the most frequently encountered ABDs in the northeast of Romania, with a higher incidence than in Western European countries, and this may be due to specific peculiarities of the geographical area, as well as to a genetic susceptibility of the population in this region.
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Basal cell carcinoma (BCC) is the most common form of cutaneous neoplasia in humans, and dermoscopy may provide valuable information for histopathological classification of BCC, which allows for the choice of non-invasive topical or surgical therapy. Similarly, dermoscopy may allow for the identification of incipient forms of BCC that cannot be detected in clinical examination. The importance of early diagnosis using the dermoscopy of superficial BCC forms is proven by the fact that despite their indolent clinical appearance, they can be included in high-risk BCC forms due to the rate of postoperative recurrence. Nodular pigmentary forms of BCCs present ovoid gray-blue nests or multiple gray-blue dots/globules associated with arborized vessels, sometimes undetectable on clinical examination. The management of BCC depends on this, as pigmentary forms have been shown to have a poor response to photodynamic therapy. High frequency ultrasound examination (HFUS) aids in the diagnosis of BCC with hypoechoic tumour masses, as well as in estimating tumour size (thickness and diameter), presurgical margin delineation, and surgical planning. The examination is also useful for determining the invasion of adjacent structures and for studying local recurrences. The use of dermoscopy in combination with HFUS allows for optimisation of the management of the oncological patient.
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Systemic sclerosis (SSc) is a collagenosis characterized by excessive deposition of collagen in the skin and viscera, in a background of immune disorder. The immunological profile of SSc often shows elevated levels of antinuclear antibodies (ANAs). However, many authors have identified cases of SSc having normal ANA levels, framed as paraneoplastic SSc. Among patients with negative ANAs in our group, we did not identify any neoplastic process that could support this hypothesis. The extended detection of autoantibodies is extremely useful in establishing the subset of SSc. Thus, anti-Scl70 antibodies are specific for the diffuse subset of SSc, while anticentromere antibodies (ACAs) have specificity for a limited subset. However, studies have shown the existence of cases of diffuse SSc having high titers of ACAs and cases of limited SSc with high titers of anti-Scl70 antibodies. This indicates an inconsistent association between the disease subset and the autoantibodies specific to each subset. Our study found a more balanced consistency between disease subsets and autoantibodies specific for each subset. Therefore, the percentages of patients having an immunological profile inconsistent with the subset of SSc, are lower than those found by other authors. This observation opens the perspective of larger studies on the immunological profile in SSc.
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Systemic sclerosis (SSc) is a relatively rare autoimmune disease with skin and visceral involvement, having a yet unknown etiopathogenesis. Research has shown that professional exposure to various polluting chemicals such as dyes, aliphatic and aromatic organic solvents, inhalable silica dust or certain heavy metals, can be triggering factors for this disease when they overlap a predisposing genetic profile. Smoking is still a debated factor involved in the etiology of SSc, as authors have divergent opinions on this matter. The present study was designed to analyze the etiological factors identified in the group of 37 patients with diffuse and limited SSc from the southeast region of Romania and the results were compared to the literature data. In the group of patients included in this study, occupational exposure and smoking history were not present in all patients, and a hereditary factor was identified only in an isolated case. The majority of patients suffered from a major negative psychological event or from long-term stressful situations and these factors were associated with smoking history or occupational exposure; this suggests that SSc is initiated in a set of cumulative triggering factors.
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Common chronic conditions, such as cardiovascular diseases and psoriasis, are associated with increased psychological distress. Health-related quality of life and personality type in patients with these two diseases were evaluated, including the patient's ability to respond truthfully or his/her tendency to be introverted or extroverted. The subjects (n=63) responded to questionnaires including: SF-36 questionnaire, Eysenck test and the questionnaire of the affective distress profile designed to assess the subjective dimension of functional negative emotions, dysfunctional negative emotions and positive emotions. Psoriasis patients had significantly higher average scores of physical functions and limitations brought on by emotional problems. Emotional instability was common for both types of patients and anxiety was associated with a low level of education. Overall, we believe that it is necessary to include items evaluating the patients' affective profile and personality in the assessment protocols of these diseases. These items could help the clinician in identifying possible factors that signal worsening of the disease or of non-response to treatment.
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Plaque psoriasis is a chronic, immune-mediated disease, which has a multifactorial etiopathogenesis. Practical non-invasive techniques to monitor plaque psoriasis progression and treatment are necessary. Imaging techniques available for psoriasis assessment may vary in terms of resolution, depth of penetration and visual representation. This review summarizes the current developments in the field of psoriasis non-invasive imaging techniques, such as dermoscopy, conventional ultrasound and high frequency ultrasonography (HFUS), videocapillaroscopy (VC), reflectance confocal microscopy (RCM), optical microangiography (OMAG), laser Doppler imaging (LDI), multiphoton tomography (MPT) and optical coherence tomography (OCT). The aim was to collect and analyze data concerning types, indications, advantages and disadvantages of modern imaging techniques for in vivo psoriasis assessment. We focused on two main methods, videodermoscopy and HFUS, which can be included in daily dermatologists' practice and which may assist in establishing diagnosis, as well as monitoring response to topical and/or systemic therapy of psoriasis. Dermoscopy may be useful for a first evaluation and may offer an understanding of the type and distribution of blood vessels, as well as the color of the scale and the background of the lesion. Videodermoscopy allows magnification and offers a detailed evaluation of the vessel type. The utility of HFUS consists mainly in monitoring therapy response. These methods may be comparable with virtual histopathology.
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The place of pemphigus vulgaris (PV) among autoimmune bullous dermatoses is well known. In pemphigus, IgG autoantibodies are directed against desmogleins 1 and 3, which are part of the cadherin family of cell-cell adhesion molecules. These structures are responsible for maintaining the intercellular adherence in stratified squamous epithelia, such as the skin and oral mucosa. The incidence of autoimmune bullous dermatoses is steadily increasing, being associated with a high degree of morbidity. The pathophysiology of these dermatoses is very well understood, complemented by recent genetic studies. The gold standard for the diagnosis of pemphigus vulgaris is the detection of autoantibodies or complement component 3 by direct immunofluorescence microscopy of a perilesional biopsy. Early diagnosis and initiation of treatment are necessary in order to achieve a favorable prognosis. Although the first line of treatment is corticotherapy, there are no clear guidelines on dosing regimens, and long-term adverse effects are important. Corticosteroid-sparing adjuvant therapies have been employed in the treatment of PV, aiming to reduce the necessary cumulative dose of corticosteroids. In addition, therapies with anti-CD20 antibodies are used, but antigen-specific immune suppression-based treatments represent the future.