A historical review of pandemics with a dermatological perspective

We present a literature review of dermatology features in historical pandemics. A pandemic is an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and affecting a large number of people. Smallpox was the first documented pandemic, around 10 000 BC, spread by the inhalation of airborne droplets. A few days after an initial high fever, headache and fatigue, a mucocutaneous maculopapular eruption appeared, which then developed pustules and erosions. The last outbreak occurred in the USA in 1949. Smallpox was eradicated in 1980, following a vaccination programme. Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), an ongoing global pandemic. The earliest documentations were 3300 years ago. In 2020, the World Health Organization (WHO) provisionally estimated 1.5 million deaths globally. Most commonly affecting the lungs, cutaneous TB may present with inflammatory papules, plaques, suppurative nodules and chronic ulcers. Requiring long, complex antibiotic regimens, multidrug resistant TB is an increasing problem. Now extremely rare, yet still with recent outbreaks in 2021 in Madagascar, bubonic plague arrived in Europe in 1346 causing 75-200 million deaths. It is caused by the bacterium Yersinia pestis, transmitted through fleas that have fed on infected rodents. Clinical features include papules, pustules, ulcers and eschars, tender lymphadenopathy and systemic symptoms, and it responds to antibiotics. Syphilis, caused by the bacterium Treponema pallidum, is sexually transmitted. The first known outbreak was during warfare in 1494-5 in Naples, Italy. In 2020, the WHO estimated that, globally, seven million people had new infections. Primary syphilis typically produces a painless, genital ulcer (or chancre). Secondary syphilis presents with a nonitchy, maculopapular erythema over the trunk, palms and soles. Early recognition and antibiotic treatment usually lead to good outcomes. Estimated by the WHO to affect 37.7 million people in 2020, HIV is thought to have mutated from simian immunodeficiency virus by the 1960s in sub-Saharan Africa, spreading to the Caribbean and USA by the late 1960s. Initial symptoms include a fever, headache and lymphadenopathy. Dermatological features are common, including opportunistic cutaneous infections, nonspecific exanthemas, seborrhoeic dermatitis and Kaposi sarcoma. Advances in antiretroviral therapies mean people with HIV can have an excellent prognosis, although the WHO estimated in 2020 that more than 200 000 people with HIV died from concomitant TB. Since 2019, COVID-19 has had a considerable global impact on healthcare. With more than 300 million cases and 5.5 million deaths to date, some services have been overwhelmed owing to large case numbers, variable vaccine uptake, workplace changes to reduce transmission and staff shortages. Cutaneous features include perniosis, urticarial, purpuric, vesicular or maculopapular eruptions. Pandemics throughout history have been repeatedly shown to present with an element of skin involvement. We can utilize this to promote education and early recognition of these features, to facilitate diagnosis and raise awareness of the potential complications of serious diseases.

Management of acute genital ulcers, retrospective review of a tertiary Canadian centre and survey of North American Pediatric and Adolescent Gynecology care providers

Background: Acute genital ulcers (AGU) are painful ulcerations of the lower vagina and vulva. Lesions typically occur in adolescents and may be preceded by a viral illness such as Epstein-barr virus, cytomegalovirus and more recently, COVID-19. AGU is a diagnosis of exclusion, with limited data to guide investigations and treatment. We aim to retrospectively review the clinical course of patients presenting to our center with suspected AGU to characterize and evaluate local practice patterns. In addition, we survey pediatric and adolescent gynecology care providers to understand the work up and management of AGU across North America. Method(s): We performed a retrospective chart review between June 1, 2016 to June 30, 2021. Medical records were reviewed to capture demographic data, diagnostic work up and management. Data is presented descriptively, and time to resolution is compared for patients managed expectantly versus with corticosteroids using a Student's T-test. A cross-sectional survey created by study authors was distributed to members of the NASPAG. Data was summarized through descriptive statistics. Management practices between care providers were compared using Fisher's Exact test. Result(s): Overall, 25 patients were diagnosed and managed as AGU at our center during the study period. On average, patients were 13.2 years old (range 11 to 17 years). The majority (92%) reported prodromal symptoms. EBV and CMV were the most ordered serologies (64%);only 3 patients showed serologic evidence of acute viral infection. Conservative measures were recommended to 84% of patients. 40% of patients were prescribed corticosteroids. Average duration to resolution was 16.3 days, with no difference between patients managed supportively versus with corticosteroids (p=0.9). In total, 100 responses from NASPAG members were included. Most care providers reported seeing fewer than 10 patients with AGU per year (62%). Common diagnostic tests performed were herpes simplex virus polymerase chain reaction (82%), Epstein-barr virus serology (56%) and cytomegalovirus serology (47%). Most care providers recommended supportive management with topical analgesia (84%), NSAIDs (83%) and acetaminophen (64%). Topical steroids were considered by 67% based on the degree of accompanying inflammation. There was no difference in corticosteroid prescribing practices between types or location of providers (p > 0.05). Conclusion(s): Our retrospective review and survey capture practice patterns of AGU management amongst pediatric and adolescent gynecology care providers. Further collaboration is needed to prospectively evaluate the effectiveness of treatment modalities, and develop evidence-based guidelines to inform practice.Copyright © 2023

Pulmonary artery pseudoaneurysms (PAPs) in Hughes-Stovin syndrome (HSS) as an emerging concept for a potentially fatal course

Introduction: Hughes-Stovin syndrome (HSS) is a systemic vasculitis characterized by pulmonary artery aneurysms (PAA) and widespread venous and arterial thrombosis. Fatalities in HSS resulted from unforeseeable fatal suffocating hemoptysis. It is critical to early detect pulmonary involvement to take timely measures against inevitable serious life-threatening complications. Case presentation: A 27 year old Filipino male patient presented to the emergency department with an acute attack of massive hemoptysis. The markers of inflammation were elevated with anemia and a normal coagulation profile. The patient had bilateral lower limb edema with tender calf muscles. Color Doppler ultrasound revealed bilateral deep vein thrombosis. Importantly, an urgent computerized tomography pulmonary angiography (CTPA) revealed bilateral large PAAs which matched the pattern of pseudoaneurysms described by the HSS international study group (HSSISG). There was no history of iridocyclitis, recurrent oral or genital ulcers. Accordingly, the patient was diagnosed with HSS. The patient received intravenous pulse methylprednisolone (1 g/3 days), then oral prednisone (1 mg/kg/d/3 months), and monthly pulse cyclophosphamide (1 g) for three months. The patient remained symptom-free, yet on the third pulse of cyclophosphamide;he patient contracted corona virus disease-2019 (COVID-19) infection and died three weeks later from a fatal episode of massive hemoptysis. The case was discussed and the recent literature was reviewed relative to fatal hemoptysis associated with pulmonary artery pseudoaneurysms (PAPs) pattern in HSS Conclusion(s): HSS presenting with massive hemoptysis could be lifethreatening and the PAPs are considered a double edged sword. Detailed description of such rare cases is warranted for optimum future management.Copyright © 2023

EVALUATION of PATIENTS with PEDIATRIC BEHÇET'S DISEASE: A TERTIARY CENTER EXPERIENCE

Background: Behçet's disease (BD) is an systemic infammatory vasculitis characterized by recurrent oral aphthae and genital ulcers. In the course of the disease, skin, eye, musculoskeletal, nervous system and gastrointestinal system involvements can be detected. Objectives: To evaluate the clinical, laboratory and radiological fndings of pedi-atric cases diagnosed with BD. Methods: Fifty patients (0-20 years old) who were followed up with the diagnosis of BD at the Pediatric Rheumatology outpatient clinic of Uludag University Faculty of Medicine between January 2011 and July 2021 were included in our study. The patients were diagnosed according to the diagnostic criteria of the International BD Study Group. Results: Twenty-four (48%) of the patients were male and 26 (52%) were female. The mean age at the diagnosis of patients was 9 ±4.55 years (10.75±4.55 years in boys, 12.35±3.65 years in girls). Twenty patients (36.3%) had a family history of Behçet's Disease. Oral aphthae were present in 96% (n=48) patients, while genital ulcers were in 32% (n=16) (Table 1). Of the nine patients with uveitis, 6 had panu-veitis, 2 had anterior uveitis and 1 had posterior uveitis. There was no difference in the distribution of symptoms according to the gender of the patients. HLA-B51 allel was found in 39 (78%) and ANA was positive in 14 patients (28%). Immunological tests showed that serum immunoglobulins were low in 11 (32.3%) of 34 patients. Low IgG levels were detected in 6 patients, low IgM levels were in 3, and low IgA levels were in 2. Thrombus was presented in three cases (thrombus in the right ventricle in one case, in the intracranial transverse sigmoid sinus and left jugular vein in two cases). The most commonly used drug for aphthae was colchicine (n=45, 82%). The use of biological agents according to patient manifestations is shown in Table 2. In the follow-up, clinical fndings improved in 35 patients (70%) Complete improvement was detected only with biological agents in 8 patients with uveitis. One patient was operated due to the development of complicated cataracts secondary to uveitis. Three patients were diagnosed with Covid-19, one of them was followed without treatment, while two of them were treated with favipiravir at home. Three patients with Covid-19 infection were using only colchicine treatment. Conclusion: Behçet's disease is rare in childhood. Although it is not common, life-threatening complications can be observed. To reduce morbidity and complications, physicians should be aware of manifestations and rare clinical pictures of the BD.

SEVERE ACUTE VULVAL ULCERATION ASSOCIATED WITH COVID-19 INFECTION IN A SEXUALLY ACTIVE DUAL COVID-VACCINATED YOUNG PERSON: A CASE REPORT

Case A 20-year old was seen at the height of the Omicron wave of the COVID-19 pandemic with a two day history of a first episode of painful genital ulceration. Her last sexual contact was one week previously. She had no other symptoms and no medical or drug history. There was bilateral inguinal lymphadenopathy and a unilateral 1cm slightly indurated shallow vulval ulcer with slough. She was treated empirically for secondarily infected primary herpes. Three days later she presented with increased pain and negative HSV PCR and STI/ BBV tests. She had large bilateral genital ulcers (figure 1) and was admitted. Repeat swabs for HSV, VZV and syphilis were negative. She had a neutrophilia, raised CRP and negative EBV and CMV IgM. A routine nasopharyngeal swab identified SARS-CoV-2 and a full respiratory virus PCR panel was otherwise negative. She disclosed a sore throat and fevers the week before the onset of her vulval symptoms but was reassured by negative home antigen tests. She had received the second dose of an mRNA COVID-19 vaccine four months previously but no booster. She was discharged after five days and treated with a reducing course of oral steroids. At four weeks her ulcers were healing well. Discussion There are few published cases of Lipschütz ulcers associated with COVID-19 and this case adds to the burgeoning evidence of the possible dermatological manifestations of the disease and crucially it illustrates the value of prompt access to sexual health services during the pandemic. (Figure Presented).

Severe acute vulval ulceration secondary to COVID-19

A 21-year-old woman was admitted with a 3-day history of severe vulval ulceration, oedema and pain. On examination she had large deep necrotic-appearing kissing ulcers on the right and left inner labia minora, with overlying grey eschar and significant surrounding inflammation. The pain was described as agonizing, requiring opioid analgesia and catheterization for micturition. Three weeks prior, she had tested positive for SARS-CoV-2, having had mild symptoms, but her PCR was negative on admission. She had not been sexually active for several months due to dyspareunia. She was initially started on co-amoxiclav and acyclovir due to a raised C-reactive protein of 94, and white cell count of 11. Investigations were negative for Epstein-Barr virus (EBV), HIV and mycoplasma. Bacterial and viral skin swabs were negative. Biopsies were taken under general anaesthesia. Histology revealed ulceration and granulation tissue only. Bacterial and atypical mycobacterial cultures were negative. She was discharged when the ulcers had stabilized and pain was controlled. Follow-up 2 weeks later revealed full healing of the ulceration. Therefore, this is a case of reactive nonsexually acquired acute genital ulceration (AGU), also known as Lipsh€utz ulceration (Sadoghi B, Stary G, Wolf P et al. Ulcus vulvae acutum Lipsch€utz: a systematic literature review and a diagnostic and therapeutic algorithm. J Eur Acad Dermatol Venereol 2020;34 1432-9), which is likely to have developed secondary to COVID -19 in this patient. This rare form of vulval ulceration has been previously linked to infections including EBV, cytomegalovirus and mycoplasma. There have been three case reports of AGU linked to COVID -19 (Krapf JM, Casey RK, Goldstein AT. Reactive non-sexually related acute genital ulcers associated with COVID-19. BMJ Case Rep 2021;14: e242653). This is a rare and dramatic presentation that needs to be recognized by the dermatologist to aid timely diagnosis and treatment.

A review on ethnomedicinal and phytopharmacological potential of traditionally wild and endemic plant Berberis tinctoria Lesch

Introduction: Berberis tinctoria an evergreen shrub, endemic and predominantly found at a higher altitude of the Nilgiri Biosphere Reserve, India. This leaf and fruit are edible, which are also used in homeopathic remedies for countless illnesses. Objectives: B. tinctoria with diverse ethnomedicinal uses was focused in the prevailing study to detailed the phytochemical and pharmacological properties for further imminent research in this species. Materials and methods: Published data in this review were all gathered from the online bibliographical databases: PubMed, Elsevier, Scopus, Google Scholar, Web of Science, and local ethnic community peoples of Kurumba and Toda. Results: B. tinctoria was used as a Ayurvedic and homeopathy medicine by the tribal communities. The previous findings of B. tinctoria were used for skin diseases, wound healing, inflammatory, menorrhagia, diarrhea, jaundice, and a snakebites. The phytochemical studies revealed that secondary metabolites, antioxidants, and antimicrobial activity as a result of major alkaloid isoforms of berberine, berbamine, jatrorrhizine, etc. Conclusion: B. tinctoria is an important plant due to the presence of bioactive phytochemicals, especially berberine protoberberine group of benzylisoquinoline. As a result of its diverse ethnopharmacological importance, as well as numerous commercial products and novel bioactive compounds yet to be discovered for future drug discovery and development.

A case of COVID-19-related acute genital ulceration in a male.

COVID-19 is a viral infection which can present with various clinical manifestations. While it primarily affects the respiratory tract, several other manifestations including skin involvements have been reported. Dermatologic manifestations are uncommon, and its prevalence is not well-known. In COVID-19, there have been two reports of acute genital ulceration to date, and both are female. Here, we report a male patient with COVID-19 complicated by acute genital ulceration in the course of the illness.

Hydroxyurea-induced genital ulcers and erosions: Two case reports.

Hydroxyurea is a chemotherapeutic agent used for myeloproliferative disorders and sickle cell anemia that is well known to cause painful mucocutaneous ulcers, typically involving the legs or mouth. However, genital ulcerations due to hydroxyurea therapy are a rare, and likely underrecognized, adverse effect with only a few cases reported in the literature to date. Ulcers of the lower legs caused by hydroxyurea are associated with a diagnostic delay, and this is likely exacerbated in cases of genital ulceration due to a lack of awareness. Herein we present two cases of painful genital ulceration in patients on hydroxyurea therapy. In the first Case, an 87 year-old male with polycythemia vera developed an ulcer on the scrotum, which was assessed initially through virtual visits during the COVID-19 pandemic, and was refractory to topical and oral antibiotic treatments. The second case was a 79 year-old male with essential thrombocythemia and a history of persistent leg ulcers who developed erosions of the glans penis. Both patients experienced complete resolution within weeks of discontinuing hydroxyurea therapy. In conclusion, genital ulcers and erosions induced by hydroxyrea may be underrecognized in clinical practice, but if identified, withdrawal of hydroxyurea leads to quick resolution of these lesions and the associated pain.