Search

Lyme borreliosis is a frequently encountered tick-borne infection worldwide, caused by a spirochete from the Borrelia burgdorferi genoscpecies. In most cases, the initial sign of Lyme disease is the pathognomonic symptom - erythema migrans rash appearing at the site of the thick bite. Оther described cutaneous manifestations besides erythema migrans ‒ such as erythema nodosum (an acute nodular septal panniculitis), papular urticaria, granuloma annulare, psoriatic changes, lichen striatus et atrophicans, Henoch-Schönlein purpura, and morphea ‒ could potentially present as an initial/first sign of acute Borrelia burgdorferi infection. Serological testing for Lyme disease is only reliable after the initial stages of the disease. Additional PCR or serological examinations such as ELISA, immunoblot, indirect immunofluorescence examination could be performed. The diverse cutaneous manifestations of Lyme disease can lead to delays or ineffectiveness in treatment, as these symptoms may not be promptly identified as signs of the infection. Therefore, a comprehensive evaluation of the three key aspects - clinical findings, serology, and histology - is essential and should be considered collectively. We present a 78-year-old female with an acute form of Borrelia infection following a thick bite, manifesting as erythema nodosum on the lower extremities. Serology confirmed the presence of Borrelia infection, and the histological findings were indicative of erythema nodosum. The patient initially received anti-inflammatory and antibiotic medications. Reverse development of the nodules was observed after therapy with ceftriaxone, methylprednisolone, esomeprazole, and local dressings with povidone-iodine. For outpatient care, her regimen consisted of systemic reduction of the corticosteroid therapy, esomeprazole, and doxycycline. Due to the potential triggering of erythema nodosum by valsartan, it was recommended switching to an alternative medication. The rarity of erythema nodosum as an initial or first sign of acute Borrelia infection is being discussed., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Modern skin cancer pathogenesis includes new concepts such as nitroso photocarcinogenesis and nitroso-mediated photosensitivity. The above 2 new concepts are in all likelihood also modeled/determined by photocarcinogens known as nitrosamines and/or NDSRIs available as contaminants in many drugs worldwide. The phototoxicity of nitrosamines is a known nonspecific property of them, for which evidence exists as far back as 1972. Current data from 2023/2024 are completely supportive of nitrosamines identified in drugs, with genotoxicity and phototoxicity proven once again. Regulators' data on polycontamination of a drug with up to several nitrosamines at the same time are of concern. The carcinogens/mutagens in question could also act as bi-/polycarcinogens depending on whether they are metabolized or not. Permanent combined intake of potentially/actually nitrosamine-contaminated drugs appears to be key in the subsequent development of multiple cutaneous tumours, according to new findings in the literature. The localization of these tumours in areas exposed to intense solar radiation could also be seen as indirectly pointing to the presence of certain photosensitisers in the human body. Some of these nitrosamines are photocarcinogens and human carcinogens at the same time. The identification and specification of each of these genotoxic photosensitizers in drugs has yet to be further investigated in detail. The FDA identifies them currently as substances with carcinogenic potency. The clinicopathologic correlations published to date within the intake of potentially contaminated drugs are indicative of 1) the need to redefine skin cancer pathogenesis and 2) the subsequent possible introduction of complete elimination regimens against nitrosamines. We inform about another polymedication intake in a patient with arterial hypertension and diabetes mellitus, which includes the following medications: gliclazide 60 mg once daily and metformin hydrochloride 850 mg once daily, both since 24 years ; sotalol hydrochloride 80 mg since 2 years; bisoprolol fumarate 5 mg since 17 years; candesartan cilexetil/hydrochlorothiazide 16 mg/ 12.5 mg since 2 years; and lercanidipine hydrochloride 20 mg also since 2 years. Within this intake, it is notable that 1) all 6 of these drugs appear in the databases for possible availability as nitroso compounds, and that 2) this is the seventh consecutive keratinocyte tumor treated surgically (in this period). In the presented patient, surgical treatment was performed using a shark pedicle island flap for BCC of the nose, which is an ideal option for tumors with location in the alar or periralar area. An optimal postoperative outcome was achieved. This article focuses on the possible role of drug-mediated photo nitrosogenesis/ carcinogenesis of skin cancer by briefly reviewing and analyzing the available literature to date.

Despite the fact that the pathogenesis of cutaneous melanoma is shrouded in mystery, factors that have been neglected or unnoticed until now have come to the attention in recent years, and in all likelihood, they could also be pivotal. These factors, known as nitrosamines or NDSRIs, are characterized by high carcinogenic and mutagenic potency, and some of them have demonstrated these properties to human DNA as well. Unfortunately, these ingredients also turn up as contaminants in about 300 of the most widely distributed drugs worldwide. According to the most recent literature, some of these ingredients are also identified as potent photocarcinogens, as well as human carcinogens. The intake of these carcinogens in the context of polycontamination of polymedication, has been associated for years with the occurrence of melanomas. The need for cataloguing of nitrosamines , as well as their accurate labelling on drug packaging, would help to classify them even more accurately as carcinogens affecting human DNA. We present once again a patient , who developed nodular melanoma within the context of the intake of 3 potentially nitrosamine/ NDSRIs contaminated antihypertensive drugs (valsartan/ Hydrochlorothiazide/ bisoprolol). Pathogenetic aspects concerning drug-induced nitrosogenesis, photocarcinogenesis and oncopharmacogenesis of skin cancer are discussed. Nitrosogenesis' of Cancer as concept in the medical literature has been known for decades, but in relation to other forms of human cancer. Exogenously mediated drug-mediated nitrosogenesis is a logically conditioned and newly defined concept whose significance with respect to the clinical manifestation of skin cancer is only beginning to grow.

The development of cutaneous melanoma of the skin based on dysplastic nevus is not uncommon. The causes of the progression of nevi to melanomas are numerous and not well understood at present. Certain genetic and epigenetic factors have a major influence on this evolution. We describe a 46-year-old female patient with multiple dermal melanocytic nevi who developed a polypoid melanoma in one of them. After a carefully performed anamnesis, the mole that developed into melanoma was found to be localized in the dorsal area adjacent to the brassiere and underwent permanent and daily mechanical irradiation during the last 6-7 years. Around this mole there were 5 other moles with similar clinical and dermatoscopic morphology, which did not transform into melanomas and were not subjected to mechanical irritation. The patient had a dermatological examination 6 years ago and it was suggested that this lesion has to be surgically removed, which she declined. The patient was treated surgically and the lesion suspicious for cutaneous melanoma was removed in two stages according to the generally accepted AJCC/EJC recommendations. In parallel, 5 additional melanocytic nevi were removed, which histologically had features of dysplastic dermal melanocytic nevi but no signs of progression to melanoma. This article discusses the causes of nevus -associated melanomas and emphasizes the thesis of potential malignant transformation through mechanical irritation - in this case that of the brassiere. The moles localized in this area, although clinically and dermatoscopically inapparent, should be treated surgically. This painless, short-term manipulation has a preventive effect on the future development of cutaneous melanomas.

Atrophoderma of Pasini and Pierini is a rare, considered benign, skin disease characterized by single or multiple asymptomatic atrophic plaques. Lesions can occur everywhere on the body with the trunk being the most often reported affected site. It appears in the second or third decade of life and affects mostly the female population, with male to female ratio of 1:6, commonly of white European descent. Different risk factors were described in the literature - genetic predisposition, infections with Epstein-Barr virus, varicella zoster and Borrelia burgdorferi, vaccinations, local trauma and more. Since the pandemic with COVID-19, skin manifestations after the viral infection with COVID-19 were reported. After a thorough search of the existing medical literature, we believe, we present the first case of a rapid progression of Atrophoderma of Pasini and Pierini after COVID-19 infection. Due to its similarity to morphea in some aspects, the condition is often misdiagnosed, and the proper treatment is often delayed. Sometimes the dilemma "Is it atrophoderma Pasini-Pierini or is it in fact morphea?" stays, but the exact histopathological verification and the "diagnostic clues" which can be used during the examination stage, are usually enough to diagnose the condition. We present a 63-year-old female with a rapid progression of atrophoderma of Pasini and Pierini after a COVID-19 infection. The lesion that she presented with was single, asymptomatic, with central hypopigmentation and slight atrophy, with a smooth, shiny surface and ivory color, and peripheral hyperpigmentation, measured 18x5cm, without the presence of perilesional erythema. The patient was initially diagnosed clinically with localized scleroderma (morphea) and treated with hydroxychloroquine 200 mg once daily for a 5-year period without improvement. Years later two biopsies from different lesional sites were taken, resulting in absence of sclerosis and dermal atrophy, but - reduction in the thickness of the dermis with fragmentation and hyalinization of collagen fibers forming a parallel orientation, dilated vascular vessels of small caliber and reduced number of skin appendages, confirming the diagnosis of atrophoderma Pasini-Pierini. The patient's therapy was switched to methotrexate with good therapeutic response. Often, the two conditions - morphea and atrophoderma of Pasini and Pierini can be mistaken due to its clinical similarity and sometimes coexistence. Therefore, we will shortly review the existing literature with key points on the similarities and differences.

Nevus spilus is a term in the literature used for a benign pigmented cutaneous lesion, occurring shortly after birth or in the early stages of infancy. The lesion itself is very distinguishable in most cases with numerous small papules or macules on a "café au lait" background pigmentation. It can be seen on different parts of the body with predominance in the areas of the extremities. Although benign, in some cases malignant transformation can occur. Malignant melanoma arising within a nevus spilus lesion is not so unlikely anymore. We report a 36-year-old female patient with a thin cutaneous melanoma developing within a congenital nevus spilus lesion successfully treated with surgery. The complete surgical removal of melanoma and nevus spilus ensures the absence of recurrences as well as the need for follow-up of patients. This surgical approach should be discussed with patients, and clinicians' recommendations depend on 1) the morphology of the lesion, 2) the size of the lesion, 3) the localization of the lesion, and last but not least : the presence or absence of stigmatization in the patients themselves. Our main focus in this article will be on the importance of an early diagnosis and eradication of such lesions while reviewing the existing literature.

Subungual lesions present a serious challenge for clinicians. The following factors can cause certain problems in interpreting the data: 1) Changes in lesion morphology over time: It may indicate the presence of a malignant lesion (increased pigmentation over time and lack of distal growth) but may actually be a benign lesion (chronic persistent subungual hematoma). 2) Patient's medical history can be misleading or difficult to verify, especially in problematic patients, or those with mental health problems or communication disorders (e.g., Asperger's syndrome, autism, schizoid psychosis, etc.). 3) The morphology of the lesion itself can be difficult to determine in the presence of simultaneously overlapping lesions. These patient dilemmas primarily concern the differentiation between subungual hematomas from subungual melanomas. The clinicians's concerns are based on the potential for metastasis and the risk of significantly worse prognosis for patients affected by nail biopsy. We present a 19-year-old patient with a subungual pigmented lesion with a clinical/dermatoscopic suspicion for subungual melanoma. Primary complaints for about 3-4 months. Intensified pigmentation and increase in size within two months led to a partial surgical resection of the nail plate and nail bed, followed by adaptation of the wound edges with single interrupted sutures. The histopathological finding was indicative of a subungual hematoma located above a focal melanocytic hyperplasia of the nail bed, clear resection lines. After a literature review, we believe that this is the first case of a patient with simultaneously present subungual benign focal melanocytic hyperplasia overlapping with a chronic persistent subungual hematoma.

The problems with lymphangiomas in general stem from the fact that on the one hand they most often show an atypical clinical picture, and on the other hand their localization does not always allow the desired complete surgical removal. Lymphangiomas are rare and benign tumors of the lymphatic vessels. In the higher percentage of cases, they are defined as congenital malformations. The acquired type can manifest due to a variety of external factors, resulting in a benign distinct lesion, which can often be mistaken for another benign or malignant one. Although benign and even surgically treated , the recurrence rate is high. The pathogenesis of these tumours is unclear and is presumed to be due to an error in the fetal/embryonal development. Nosologically, these lesions belong to the group of so-called low flow lesions. Within the framework of their differentiation, it is important to distinguish them from hemangiomas and venous malformations, as although overlapping to some extent, at times- therapeutic options differ. This differentiation is most adequately accomplished by the application of MRI and Doppler, necessarily accompanied by histopathologic verification of the lesion. Spontaneous regression, although rare, occurs in up to 6% of cases. Surgical removal remains the safest method of treatment to date, and according to the literature this is possible in only 18 to 50% of cases. Often, however, the atypical clinical presentation of some of the lesions could be confusing for clinicians and could be the reason for prolonged and unsuccessful conservative or semi-invasive therapy. We present a 23-year-old patient with a history of complaints of more than 15 years in the form of itching, burning, and discomfort in the left foot area. The finding was treated under the diagnosis of viral warts with variable results and subsequent achievement of short-term remissions for no more than 5 -6 months. Due to an increase in pain symptomatology and an increase in the size of the lesion after the last cryotherapy, a skin biopsy was taken to confirm the diagnosis of lymphangioma. During hospitalization, the patient underwent MRI/Doppler of the vessels to determine the depth of infiltration and the presence/exclusion of communication to larger vascular formations for preoperative planning. Surgery was performed with secondary wound healing resulting in a favourable outcome.

The pathogenesis of skin cancer remains shrouded in mystery. Nevertheless, a substantial amount of new data is now available to provide a logical explanation regarding the possible link between 1) the occurrence of single or multiple acquired/somatic mutations and 2) the generation and progression of skin cancer, as well as 3) the potential association of the above two facts with the availability of nitrosamines in drugs for hypertension, diabetes, gastritis, acne, tuberculosis, various other antibiotics, etc. The nitrosogenesis of skin cancer is slowly but surely being established as a significant concept that could not be ignored for longer periods of time. It should only be analysed in detail with a view to future prevention for the benefit of public health. The nitrosogenesis of skin cancer is slowly but surely being established as a significant concept that cannot be ignored for longer periods of time. It should only be analysed in detail with a view to future prevention for the benefit of public health. Although this information has been known for decades (but in relation to the development of other cancers), there is still no comparative analysis of the mutations that occur after ingestion of a particular mutagen, also known as nitrosamine. This analysis could to some extent highlight/support or reject to some extent the thesis of the role of nitrosamines and genetic instability leading to the subsequent generation of a malignant cell clone. The notion of skin cancer nitrosogenesis should become a priority concept very soon, but it should also become an evidential memory, a byword, and an equivalent of the ignorance with which modern civilization has treated its own health for decades within the processes of globalization. It is these processes that include nitrosamines as a major component of the "medicinal and nutritional menu" of patients. It remains unclear at present why regulatory authorities are making endless attempts to legalise the availability of a number of mutagens/human carcinogens in the most commonly distributed medicines worldwide. And to persuade "others" that there is no risk from their permanent, controlled and long-term intake. The newly introduced regulatory norms in practice concern the potential/permissive availability of nitrosamines in a serious number of drugs: drugs with radically different mechanisms of action such as: ranitidine, metformin, ACE inhibitors, beta blockers, thiazide diuretics, sartans, rifampicin, but also probably a number of others. However, the occurrence of identical, similar patterns of cancers (skin cancers) following their administration (after ingestion of different classes of drugs) makes the ubiquitous permissive availability of nitrosamines (in each class of these drugs) the most potent and most likely pathogenetic inducer of cancer. These comparative patterns of skin tumor occurrence should have even stronger evidentiary value than even so-called prospective follow-ups. Nitrosamines are and remain one of the best studied mutagens/carcinogens that can alter/modify the human genome. A fact underlined repeatedly over the years (also based on in vivo data, repeatedly ignored) and a fact that, according to the literature, concerns mainly tire industry workers (British rubber workers). It is in this category of patients and after exposure to high doses of nitrosamines (potential inhalation intake) that high mortality has been found in bladder, lung, stomach, oesophageal cancer, multiple myeloma, leukaemia, prostate cancer, pancreatic cancer, and liver cancer. Similar international observations (in vivo/Sweden) concerning intensive human exposure (Swedish rubber workers) to high doses of nitrosamines in a working atmosphere (inhalation type of carcinogen uptake) emphasize the resulting direct subsequent risk of other alarming symptoms such as: nasal bleeds, eye and throat symptoms, hoarseness, cough, nausea, headache, and altered levels of eosinophils and total immunoglobulin G (IgG), compared with unexposed patients. The neglect of these important observations over the years has led to the ubiquitous and currently difficult to counteract and unpunished prevalence of nitrosamines in even the most commonly distributed drugs worldwide (except in the food industry). It is precisely because of this fact that it should come as no surprise to anyone that there is new evidence of an avalanche in the number of new cancers after ingestion of potentially nitrosamine-contaminated preparations. Skin cancer could be seen in the near future precisely as a model of a side reaction after application or long-term contact with mutagens called nitrosamines. Based on the above, and wishing to add to the worldwide data on the heterogeneous cancers that occur after contact with nitrosamines, we draw the attention of the scientific community to the risk of developing keratinocytic cancer after ingestion of nitrosamine-contaminated drugs: sartans and thiazide diuretics. We believe that the role of the generic substance in these drugs could also contribute to some extent to the progression of an already present tumour branch, but this influence is rather minor and without significant clinical relevance. We present a patient who had been taking 2 sartans (valsartan/ olmesartan) over the years as monotherapy and in combination with hydrochlorothiazide, who developed over time and within this intake two forms of keratinocytic cancer: verrucous carcinoma and basal cell carcinoma. The focus of discussion concerns a newly introduced medical concept: nitrosogenesis of skin cancer. The detailed study of nitrosogenesis should be a major, primary task for regulators, researchers, clinicians, and pharmaceutical companies.

Deciphering the mutational pattern of skin tumours, remains a major challenge for clinicians and researchers. Over 80% of mutations in tumours are acquired, which in practice also means preventable. The surgical treatment of skin cancer and cancer in general is a worldwide, unsolved but at the same time not unsolvable problem. The problem concerning the dilemma of acquired mutations lies in the circumstance of their being allowed and subsequently treated. A more logical solution would be to eliminate the problem by making contact with mutagens in drugs public, clarifying it, studying it in detail and definitively stopping it. At present, there is an alarming and unexplained tendency worldwide : 1) Potential acquired mutations, caused in all probability by contact with known exogenous mutagens- the nitrosamines in most commonly prescribed drugs, are allowed to occur. 2) And subsequently, the diseases generated by them- treated (at a later stage) by multiple surgical interventions and unjustifiably expensive targeted therapy; 3) Mutagens - such as nitrosamines for example, to be in a permissive or possibly permissive availability regime. Moreover, this permissible availability turns out to be ubiquitous and affects the most common medicines worldwide: metformin, ranitidine, propranolol, rifampicin, irbesartan, olmesartan, valsartan, telmisartan, eprosartan, losartan, ACE inhibitors, thiazide diuretics, etc. In certain geographical regions, there is almost no patient taking this type of medication who has not had at least one tumour detected. These significant correlations (nitrosamines/cancer) are labeled by the regulatory institutions as possible, probable, or not currently relevant. But in spite of ˝this inconclusiveness˝, the drugs, containing nitrosamines, are withdrawn from the pharmaceutical market: quickly and quietly, despite the fact that ˝they did not pose a threat˝. The FDA was the only organization and the most important regulatory body worldwide, which lifted the veil from this ominous picture back in 2018: nitrosamines in blood medicines and cancer risk. Unfortunately, at the moment, the problems with this issue are proving to be more than the solutions, and at the same time it remains completely unclear who is to blame for this 'sporadic contamination': the packaging of the drug, the humidity in the rooms where the preparations are stored or the synthesis process itself - the explanations are divergent, the responsibility is blurred. This fuzzy liability does not affect the manufacturers and distributors of the preparations/nitrosamines themselves in the manner required by law for this (mis)act. The Bulgarian Society of Dermatological Surgery remains to be the only organization worldwide that for the 5th consecutive year continues to seek solutions to the above-mentioned problems by: 1) Officialising all cases of skin tumors (but not only) occurring after intake of nitrosamine-contaminated drugs, 2) also officialising a significant number of cases of patients with cutaneous melanomas treated by the one-stage surgical removal method within one surgical session (OSMS). The main priorities of the organization remain: 1) the complete elimination of nitrosamines from drugs worldwide, 2) the optimization of melanoma surgical treatment guidelines with the goal of treatment within 1 surgical session: for thin melanomas, dysplastic nevi and melanoma in situ, a surgical margin of safety of 1 cm in all directions and without detection and removal of the draining sentinel lymph node. Whereas for medium and thick melanomas, the focus should be directed to the following recommendation: 2 cm surgical margin of safety plus detection and removal of the draining lymph node within one surgical session. The indication for the surgical removal of these lesions should be made on the basis of radically different criteria from those used to date by the AJCC/EJC, namely: based on 1) clinical presentation/ clinical morphology, 2) dermatoscopic finding, and if there is a melanoma suspected lesion with possible tumour thickness greater than 1 mm , 3) ultrasonographic measurement for preoperative determination of tumor thickness should be additionally performed. The methodology is applicable in up to 80% of cases, excluding only some rare findings such as: amelanotic cutaneous melanomas, cutaneous melanomas with regression zones or those with localization in the neck and head. However, after careful individual assessment and a subsequent selected approach, even these exceptions could be included in the innovative algorithm for one step surgical removal of cutaneous melanomas. The resulting problems of not resolving these two dilemmas could lead to: 1) Generation of skin cancer (but not only), through the availability of nitrosamines in drugs. 2) Unnecessary and stressful /surgeries for the patients- 2 in number, which not infrequently lead to complication of their status (due to delay of histopathological analysis/ desire for second opinion/ delay regarding the timeframe for the second surgical intervention/ uncertainty regarding the resection lines within the first intervention/ failure to respect the recommended surgical security resection margins already within the first surgical session, etc.). 3) Huge additional costs to health care systems on the order of probably/roughly calculated about $50 billion per year. Resolution of these two dilemmas would likely result in a dramatic drop in cancer incidence worldwide and a significant improvement in the effectiveness/efficiency of surgical treatment for cutaneous melanoma.

Melanocytic lesions, especially in delicate anatomical locations such as the vulva, penis, mons pubis etc , are challenging to diagnose. The patients may delay physical examinations due to anxiety or discomfort from the location of the lesion. In terms of therapy options, the surgical approach is not always the preferred one, but it is the one that could lead to a definitive solution to the problem. A limited number of studies do not exclude that atypical nevi of genital type could be considered as melanoma precursors. Single case reports have identified atypical genital nevi of the labia majora as a risk factor for genital melanoma development. Lesions that occupy a larger area than the labia majora and extend into the areas around them are particularly problematic, because the result of a single biopsy could be misleading. Therefore, careful physical examinations are mandatory. Mechanical irritation in the genital area, and in particular in the labia majora region, is an additional reason for choosing the surgical-reconstructive therapeutic option. We present a 13-year-old female with a progressive kissing divided nevus, located in the area of the vulva and labia majora, extending to the mucosa. A biopsy was taken in order to rule out malignancy. Immunohistochemistry was performed with specific melanocyte markers S-100, HMB-45 and SOX confirming the benign origin of the lesion. A diagnosis of atypical melanocytic nevus of genital type was made. For prevention a surgical excision was advised but later on declined by the patient's parents. Further close observation of the lesion was recommended., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest., (©Copyright: the Author(s).)

Giant keratinocyte tumors, in particular basal cell carcinomas of the scalp area, are a serious challenge for dermatosurgeons, oncologists, and maxillofacial and reconstructive surgeons. The scalp area is limited in terms of skin mobility, and its elasticity decreases with age. The size of the tumors in this area and the degree of infiltration of the underlying tissues are important for the therapeutic choice, from surgical removal, waiting for granulations to form, and placing a split skin mesh graft (at a later stage) to performing complex rotational/transpositional or advancement flaps. Achieving an optimal aesthetic result is often the consequence of interventions carried out or based on the decisions of multidisciplinary teams. Alternatives, such as radiotherapy and targeted therapy with vismodegib, could be administered both preoperatively and postoperatively or as first-line therapy, depending on the tumor board decisions. We present the case of a 69-year-old female patient with a histopathologically proven preoperative giant basal cell carcinoma of the scalp that did not infiltrate the tabula externa. A preoperative ultrasound was performed to preserve the feeding flap arteries. Surgical treatment under general anesthesia was planned and subsequently carried out. During surgery, the surgical resection lines were in close proximity to the arterial vessels, but they remained preserved and ensured a subsequently unproblematic healing process. After the application of the rotational advancement flap technique under general anesthesia, an optimal cosmetic effect was achieved., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest. Patient consent for publication: the patient in this manuscript has given written informed consent for further publication of her case details., (Copyright © 2023, the Author(s).)

Chronic recurrent urticaria, occurring in the context of infections, represents a major challenge for clinicians. Chronic genital herpes infection has been perceived in the literature as a possible trigger of chronic recurrent urticaria. The administration of a systemic corticosteroid regimen in these cases has no long-lasting effect and the subsequent relapses are difficult to control. In these cases, treatment of the urticaria with antihistamine (as monomedication) is often not sufficient and does not suppress the symptomatology. The administration of acyclovir or valacyclovir according to a specific therapeutic regimen as monotherapy or in combination with antihistamine has been shown to be quite effective. The doses of this administration vary and can be tailored to clinical symptomatology. We present a 41-year-old female patient with chronic recurrent urticaria associated with angioedema and bronchospasm, in whom her herpes genitalis was found to be concurrent within the history and clinical examination. According to the history, the herpes was also recurrent and dated back about a year. Chlamydia trachomatis infection was also found, with serological findings corresponding to vaginal discomfort. Treatment with acyclovir 400mg thrice daily for an initial period of 7 days in combination with desloratadine 5mg daily was started as we observed complete remission of the urticarial rash. Due to worsening vaginal discharge, it was decided to temporarily discontinue systemic acyclovir therapy and treatment for the chlamydial infection was initiated with doxycycline 100 mg twice daily for 21 days. Already on day 1 after stopping acyclovir, a severe relapse with generalization of the urticarial rash was observed. Control of symptomatology was achieved by reintroduction of acyclovir according to the regimen in combination with antihistamine. Chronic infections are one of the common causes of chronic recurrent urticaria with a tendency to generalization and possible complications such as angioedema and bronchospasm. An academic, analytical approach to patients and the consistent exclusion of each possible trigger for chronic recurrent urticaria often guarantee the success of subsequent treatment., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest. Patient consent for publication: received., (Copyright © 2023, the Author(s).)

Post-vaccinal and parainfectious activation of the immunity with subsequent development of a certain immunological/skinimmunological disease is not rare in clinical practice. This concept is mentioned in relation to molecular/antigenic mimicry. To this day, the pathogenesis of sarcoidosis and sarcoid-type reactions remains a mystery. Moreover, they can be a warning sign of changes in tissue homeostasis, whether they are infectious, noninfectious- immunological, tumor-related, etc . We present a rare form of erythrodermic sarcoidosis with massive systemic involvement (pericarditis, supraventricular tachycardia, hepatitis, iritis/iridocyclitis, pulmonary fibrosis/bihilar lymphadenopathy, and arthritis) developed after receiving the ChadOx1-S vaccine for COVID- 19. Systemic immunosuppressive therapy with Methylprednisolone was introduced according to a scheme (in a reduction mode with an initial dose of 40 mg/day intravenously) in combination with topical Pimecrolimus 1% cream twice a day. Rapid improvement of the symptoms was observed within the first two days of treatment. According to the scientific literature, the presented patient turns out to be the first case of erythrodermic sarcoidosis (with systemic involvement), described as a side effect after vaccination and/or administration of a certain medicinal form., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest. Patient consent for publication: informed consent was obtained from all individuals included in this study. The patients in this manuscript have given written informed consent to the publication of their case details., (©Copyright: the Author(s).)

Nitrosamines as contaminants in a wide variety of drugs are also found to be one of the most likely causes of skin cancer. A detailed analysis of this contamination could in the near future solve to a large extent the puzzle of carcinogenesis concerning the keratinocytic forms of cancer and melanoma. But also, probably cancer in general. Over 80% of skin cancer is due to acquired mutations, and nitrosamines, which are contained as contamination in certain batches of the most commonly distributed drugs worldwide (such as sartans, ACE inhibitors, ranitidine, metformin, hydrochlorothiazide, rifampicin, and a number of others.) are considered among the most powerful external mutagens, carcinogens. Carcinogens that until 2021 were not supposed to be present in medicines and carcinogens for which it was subsequently decided to create a regulatory regime for permissible availability. Regardless of whether these contaminants are applied within the so-called daily acceptable intake dose or many times above it, the problem with the availability of nitrosamines continues to be present. It is also caused by the lack of reflection of the concentration of the corresponding nitrosamine in a certain drug. Thus, it is impossible to calculate the ˝permissible daily intake of the total number of mutagens and their concentration based on polymedication˝. In practice, drug manufacturers distribute nitrosamines in parallel with drugs, although they are not listed as a component of the product but are identified and allowed as contamination or substances with permissible availability by the EMA/FDA. From another point of view, the fact that is not commented on is also of interest, namely that not all batches are affected by this contamination. This suggests that the contamination may have been controlled, since in a manufacturing error the contamination should be widespread. The registration of the potential contamination of a heterogeneous type of medicinal products on the European market to the executive agencies for drug control in certain geographical areas has remained for years without any answer and opens a number of questions. The problem with ACE inhibitors is similar to that with sartans, hydrochlorothiazide, metformin, and ranitidine. The ˝special impression˝ of the clinicians is determined by the fact that the patterns of manifestation of the skin tumors during the administration of a heterogeneous class of medications are similar to completely identical. From this it could be concluded that the unifying factor between the pattern of occurrence could not be based on the action of the main substance of each drug class, since it remains to be radically different. The unifying link remains the sole and only contamination or the permissible already availability of a new ingredient known as nitrosamines. We present cases of multiple basal cell carcinomas and dysplastic nevi following enalapril and perindopril administration. The role of potential contamination of ACE inhibitors with nitrosamines for the development of skin cancer is discussed.

The pathogenesis of keratinocytic skin cancer has been well-studied over the years, with a main focus on the influence of UV radiation and the subsequent changes in the genome regulator p53, which affects the cell cycle and the programmed cell death, apoptosis. Alarming and relatively new trend is the link between nitrosamines in blood pressure medications (but not only) and the development of both melanocytic and keratinocytic skin tumors. In the recent past, high concentrations (above the so-called daily acceptable intake dose) of nitrosamines in ACE inhibitors and sartans became the reason for some of these medications to be officially withdrawn from the drug market. As of now, and according to the lawsuits filed, contamination with even or just one nitrosamine could be the cause of lawsuits for between 5 to 10 forms of cancer overall. Single case reports, but also large-scale retrospective international studies, find a connection between the intake of possibly nitrosamine contaminated ACE inhibitors/sartans with the subsequent development of basal cell carcinomas. The same studies also found a serious risk of developing melanomas and squamous cell carcinomas after taking ACE inhibitors, thiazide diuretics and sartans. This, in turn, leads clinicians to ponder the following dilemma: Is it possible that the key pathogenetic link concerning the development of skin cancer is due to their radically different mechanism of action (ACEs/ARBs/Thiazides)? Or, more likely, in all three antihypertensive drug classes, such as sartans, ACE inhibitors, and thiazide diuretics, there is another cancer-causing contaminant, the so-called nitrosamines? Systemic intake of potentially nitrosamine-contaminated sartans and ACE inhibitors would logically lead to the generation of relatively uniform skin tumors. Proceeding precisely from this thesis, we present two non-related cases of metatypical basal cell carcinomas in the nasal area, which occurred during the administration of ACE inhibitors/angiotensin receptor blockers and were successfully treated by transpositional reconstructive flap - bilobed flap. Possible contamination with nitrosamines as a pathogenetically significant factor is discussed.

Fixed drug eruptions (FDEs) are adverse drug reactions manifesting in the skin after exposure to a certain drug. The lesions can manifest as single or multiple eruptions followed by a post-inflammatory hyperpigmentation. The condition is very common among the young adult population and can be located on different parts of the body: the trunk, extremities, face, lips, etc. We report a case of a multifocal FDE following oral intake of Loratadine, Cetirizine dihydrochloride, Ibuprofen and/or Acetylsalicylic acid. Patch testing was recommended but later on declined by the patient. However, a small punch biopsy confirmed the diagnosis of multifocal fixed drug eruption. The lesions are often misdiagnosed or mistaken for other skin conditions. Differential diagnosis with an acquired dermal melanocytosis or other cutaneous eruptions could be done. Therefore, a brief review of the above-mentioned medications in the pathogenesis of the condition will be discussed.

Competing Interests: Conflict of interest: The authors declare no potential conflict of interest.

Erosive pustular dermatosis of the scalp (EPD) is a rare condition that affects predominantly the adult population and occurs on a previously photo-damaged bald scalp. The physical examination is presented with large erythematous, erosive and crusted patches with granulation on an atrophic skin. The problem in patients with erosive pustular dermatosis of the scalp arises from the non-specific clinical and histopathological findings, which can be misleading. Biopsy followed by careful histopathological verification is mandatory, although the finding is nonspecific. The histopathology findings are characterized by superficial erosions with mild neutrophil infiltrate, mainly intravascular and focally with neutrophil exocytosis; focal parakeratosis, smoothed rete ridges without pronounced interface changes; pronounced lymphoplasmacytic infiltrate with focal distribution in the dermis and giant cell reaction with the formation of a "foreign body" granuloma.. We report a 58-year-old male patient with a 1-year-old lesion, suspected for skin cancer, later diagnosed with EPDS, which was successfully treated with topical clobetasol proprionate after 3-5weeks., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)