The role of scoliosis on the comorbidity and demographics of neurofibromatosis type 1 patients: A retrospective analysis of the National Inpatient Sample database.

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome in the United States, affecting every 1 in 3000 individuals. NF1 occurs due to non-functional mutations in the NF1 gene, which expresses neurofibromin, a protein involved in tumour suppression. As a result, NF1 typically presents with non-cancerous neoplasm masses called neurofibromas across the body. Out of all NF1 abnormalities, the most common skeletal abnormality seen in around 10%-30% of NF1 patients is scoliosis, an improver curvature of the spine. However, there is a lack of research on the effects of scoliosis on demographics and morbidities of NF1 patients. We performed a national analysis to investigate the complex relationship between NF1 and scoliosis on patients' demographics and comorbidities. We conducted a retrospective cross-sectional analysis of the 2017 US National Inpatient Sample database using univariable Chi-square analysis and multivariable binary logistic regression analysis to determine the interplay of NF1 and scoliosis on patients' demographics and comorbidities. Our query resulted in 4635 total NF1 patients, of which 475 (10.25%) had scoliosis and 4160 (89.75%) did not. Demographic analysis showed that NF1 patients with scoliosis were typically younger, female and white compared to NF1 patients without scoliosis. Comorbidity analysis showed that NF1 patients with scoliosis were more likely to develop malignant brain neoplasms, epilepsy, hydrocephalus, pigmentation disorders, hypothyroidism, diabetes with chronic complications and coagulopathy disorders. NF1 patients with scoliosis were less likely to develop congestive heart failure, pulmonary circulation disease, peripheral vascular disease, paralysis, chronic pulmonary disease, lymphoma and psychosis. NF1 patients with scoliosis were predominantly younger, female, white patients. The presence of scoliosis in NF1 patients increases the risks for certain brain neoplasms and disorders but serves a protective effect against some pulmonary and cardiac complications.

Extramammary Paget Disease. Part I. Epidemiology, Pathogenesis, Clinical Features, and Diagnosis.

Extramammary Paget disease (EMPD) is a rare skin cancer of apocrine-rich skin that mimics common inflammatory and infectious dermatoses, leading to delays in diagnosis and increased patient morbidity. Better clinical recognition of this entity, multidisciplinary patient assessment, and deeper understanding of the underlying pathophysiology are essential to improve patient care and disease outcomes. It is important to distinguish primary intraepithelial/micro-invasive EMPD from invasive EMPD or cases with adenocarcinoma arising within EMPD. This 2-part continuing medical education series provides a complete picture of EMPD. Part 1 of this continuing medical education series reviews the epidemiology, oncogenesis, clinical and histopathologic presentation, workup, and prognosis of this rare cancer.

Post-COVID-19 neuropsychiatric manifestations: a suggested therapeutic approach to 'long COVID' with azithromycin.

The devastating effects of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may not end when the acute illness has terminated. A subset of COVID-19 patients may have symptoms that persist for months. This condition has been described as 'long COVID'. From a historical perspective, it has been recognized that serious long-term neurological sequelae have been associated with RNA viruses such as influenza viruses and coronaviruses. A potential intervention for early post-COVID-19 neuropsychiatric impairment may be the commonly employed, readily available, reasonably priced macrolide antibiotic, azithromycin. We have observed a favourable clinical response with azithromycin in three patients with neurological symptoms associated with long COVID-19. We recommend considering formal clinical trials using azithromycin for patients with post-COVID-19 infection neurological changes including 'COVID fog' or the more severe neurological symptoms that may later develop.

Neurofibromatosis type 1: New developments in genetics and treatment.

Neurofibromatosis type 1 is the most common neurocutaneous syndrome, with a frequency of 1 in 2500 persons. Diagnosis is paramount in the pretumor stage to provide proper anticipatory guidance for a number of neoplasms, both benign and malignant. Loss-of-function mutations in the NF1 gene result in truncated and nonfunctional production of neurofibromin, a tumor suppressor protein involved in downregulating the RAS signaling pathway. New therapeutic and preventive options include tyrosine kinase inhibitors, mTOR inhibitors, interferons, and radiofrequency therapy. This review summarizes recent updates in genetics, mutation analysis assays, and treatment options targeting aberrant genetic pathways. We also propose modified diagnostic criteria and provide an algorithm for surveillance of patients with neurofibromatosis type 1.

Neurosyphilis and the Jarisch-Herxheimer reaction: A therapy concern with HIV disease.

Jarisch-Herxheimer reaction (JHR) should be anticipated in treating neurosyphilis with coexistent human immunodeficiency virus (HIV) encephalitis. In that context we have devised a staging classification for JHR. In addition, an illustrative case is provided to emphasize the need to consider the diagnosis of neurosyphilis in HIV patients, and if delineated, to be prepared for a severe JHR.

COVID-19: Topical agents and therapeutic prevention of nasal viral acquisition.

Since the spread of SARS-CoV-2 became a pandemic, the number of cases has been continuously growing worldwide. Numerous recommendations and suggestions have been published to prevent the acquisition and spread of the SARS-CoV-2, especially to protect health workers and front-line caregivers. SARS-CoV-2 is transmitted by aerosol, rendering air defense with suitable ventilation and adequate mask use pivotal. Recently, locally applied antiseptic, antiviral, or structure competitive receptor blockers were suggested to attack the virus at its main point of invasion, the nasal mucosa and nasopharynx. We discuss the most plausible and safe ideas to reduce viral load at the point of entry, and subsequently the spread of SARS-CoV-2 to the lower respiratory tract, lungs, and other organs. In addition, we analyze the value and recommend clinical trials employing topical trichloroacetic acid (TCA), a substance well known from dermatologic and cosmetic procedures. It has been proven to successfully block the nasal entry for airborne allergens, preventing the development of allergic rhinitis and asthma, and to be curative for early stages of viral infections entering through the oral mucosa. For SARS-CoV-2, TCA in a single, short-time application is expected to remodel the nasal and nasopharyngeal epithelia, eliminating both the receptors and cells responsible for viral entry and subsequent viral spread to the lower respiratory tract. Moreover, this may have therapeutic benefits for those recently infected by reducing local viral replication. Such procedures are cheap, safe, and can be conducted in almost every setting, especially in regions with inadequate financial and logistic resources.

Leiner's disease (erythroderma desquamativum): A review and approach to therapy.

Leiner's disease (LD) is a rare and serious syndrome of infantile erythroderma of severe and progressive generalized seborrheic-like dermatitis, recalcitrant diarrhea, malabsorption and wasting, and recurrent local and systemic infections. The purpose of this study is to provide an updated review on management with a summarized review of available peer-reviewed articles on LD. The mechanisms underlying this disease process remain unclear. The diagnosis includes demonstration of deficient opsonic activity along with the clinical tetrad of erythroderma, persistent gastrointestinal disturbance, superimposed bacterial or candidal infection, and marked wasting. An important correlation between LD and defective yeast and Staphylococcus aureus opsonization has been established. For the familial form of LD, an association of either complement three deficiency or complement five dysfunction has been made. LD should be distinguished from other types of infantile erythroderma, including Omenn syndrome. Treatment includes fluid and nutrition replacement, antibiotics to control infection, and fresh-frozen plasma therapy. The prognosis is unclear; it depends on treatment. LD is a life-threatening condition that requires prompt identification and hospitalization. Affected infants who receive vigorous treatment not only have the prospect of surviving, but also generally lead a normal life after infancy.

Recognition and treatment of devastating vasculopathic systemic disorders: Coronavirus disease 2019 and rickettsioses.

Cutaneous involvement can be an important sign of both COVID-19 and rickettsioses. Rickettsial infections may be first evident as an exanthem with eschars as a key finding. In contrast, eschars and necrotic lesions can be seen in critically ill COVID-19 patients. Both illnesses share a similar mechanism of infecting endothelial cells resulting in vasculopathy. Rickettsia parkeri and Rickettsia 364D are both characterized by eschars unlike Rickettsia rickettsii. Other eschar causing rickettsioses such as Rickettsia conorii, Rickettsia africae, and Orientia tsutsugamushi are commonly diagnosed in people from or having traveled through endemic areas. While there is no consensus on treatment for COVID-19, rickettsioses are treatable. Due to possibly serious consequences of delayed treatment, doxycycline should be administered given an eschar-presenting patient's travel history and sufficient suspicion of vector exposure. The proliferation of COVID-19 cases has rendered it critical to differentiate between the two, both of which may have overlapping vasculopathic cutaneous findings. We review these diseases, emphasizing the importance of cutaneous involvement, while also discussing possible therapeutic interventions.

Microcystic adnexal carcinoma of the head and neck: Characteristics, treatment, and survival statistics.

Studies on microcystic adnexal carcinoma (MAC) survival rates have been limited. This effort examines the association of patient demographics, treatment modalities, and tumor stage with overall survival (OS) in patients with MAC of the head and neck. All cases of MAC with primary sites of the skin of the head and neck, confirmed histologically, and diagnosed from 2004 to 2016 in the National Cancer Database, were analyzed. We utilized Kaplan-Meier and Cox proportional-hazard models to analyze the characteristics and survival outcomes of the 415 cases that met the criteria. The mean age of diagnosis was 63.8 years (SD ±15.8). Mean OS was 10.8 years with 5- and 10-year OS being 81.0% and 68.0%, respectively. Women were more frequently affected (59.0%; P < .001). Stand-alone primary site surgery was the most common treatment (81.4%): 15.9% of patients were treated with postexcision radiation therapy (RT). 18.3% were treated with RT with or without surgery and/or chemotherapy. RT was independently associated with a decreased hazard of death (HR = 0.23; P = .044). MAC of the head and neck disproportionately affects whites, is more common in women, and has the potential to metastasize. Surgical excision is the commonest treatment; our study shows benefit from judicious RT.

Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice.

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.

Emerging drugs for the treatment of vitiligo.

Introduction: Vitiligo is a relatively common autoimmune depigmenting disorder of the skin. There has been a great advance in understanding the pathological basis, which has led to the development and utilization of various new molecules in treating vitiligo. This review aims at a comprehensively describing the treatments available and the emerging treatment aspects and the scope for future developments.Areas covered: This study comprehensively summarizes the current concepts in the pathogenesis of vitiligo with special focus on the cytokine and signaling pathways, which are the targets for newer drugs. JAK kinase signaling pathways and the cytokines involved are the focus of vitiligo treatment in current research, followed by antioxidant mechanisms and repigmenting mechanisms. Topical immunosuppressants may be an alternative to steroids in localized vitiligo. Newer repigmenting agents like basic fibroblast growth factors, afamelanotide have been included and a special emphasis is laid on the upcoming targeted immunotherapy.Expert opinion: The treatment of vitiligo needs to be multimodal with emphasis on targeting different limbs of the pathogenesis. Topical and oral JAK inhibitors are the most promising new class of drugs currently available for treating vitiligo and acts best in conjunction with NB-UVB.

Disseminated intravascular coagulation: A devastating systemic disorder of special concern with COVID-19.

Disseminated intravascular coagulation (DIC) is linked with severe COVID-19, prompting considerable concern. DIC can be a devastating systemic disorder. It is often markedly manifest on the skin as acrocyanosis or as petechiae and purpura with progression to hemorrhagic bullae. Subcutaneous hematomas may occur, as may thrombotic findings including necrosis and gangrene. The most common cause is infection, with special emphasis now on COVID-19. We have reviewed the medical literature under the search terms "Disseminated intravascular coagulation" and "consumption coagulopathy" for the past two decades in the English language using Medline and Google Scholar to update special concerns and considerations, focusing on those with COVID-19. Skin findings with DIC may be prominent. The severity of cutaneous lesions often correlates with the gravity of systemic disease. DIC is most effectively treated by addressing the underlying cause and resuscitating the patient using supportive measures. It is pivotal to recognize and treat DIC early, before deadly complications, such as multiple organ failure, arise.

COVID-19 with dermatologic manifestations and implications: An unfolding conundrum.

The novel coronavirus SARS-CoV-2 has caused Coronavirus Disease 2019, widely known as COVID-19, now a pandemic with extraordinary infectivity, mortality, and fomite adhesiveness. We delineate cutaneous manifestations of COVID-19, some of which may represent adverse cutaneous drug reactions, and skin changes associated with COVID-19 lifestyle alterations in patients and health care workers. We review COVID-19 from both a dermatologic and public health perspective.

Cutaneous manifestations of a 21st century worldwide fungal epidemic possibly complicating the COVID-19 pandemic to jointly menace mankind.

In view of the new viral COVID-19 pandemic, the fungal Candida auris epidemic still in progress worldwide highlights non-Candida albicans candidal infections. We describe an immunocompetent woman with a cutaneous manifestation of Candida parasilopsis fungemia, a prominent eschar, which proved to be the nidus for the candidemia. We stress the value of selectively removing eschars. C. parasilopsis and C. auris are increasingly important causes of sepsis and wound infections. We emphasize that commercially available biochemical-based tests may misidentify C. auris as C. parapsilosis, and stress the added danger of C. auris to critically ill-hospitalized COVID-19 patients. Any health care facility with evidence of infection or colonization with C. auris requires very close monitoring, since this fungus is a nosocomial threat comparable to SARS-CoV-2 in its mortality and fomite adhesiveness! Both organisms have the potential to be transmitted as nosocomial pathogens; health care workers need to follow strict CDC guidelines. During this COVID-19 pandemic, every health care facility should closely monitor for the possible deadly combination of the SARS-CoV-2 and C. auris. The identification of C. auris necessitates use of sophisticated technology not readily available to make this essential diagnosis since C. auris is multi-drug resistant and isolation precautions would become paramount.

Generalized pustular figurate erythema: A newly delineated severe cutaneous drug reaction linked with hydroxychloroquine.

A severe cutaneous drug reaction resembling acute generalized exanthematous pustulosis resulting from ingestion of hydroxychloroquine has been documented. It is distinguishable by its longer incubation period, more varied morphology with initially urticarial and later targetoid and arcuate plaques, recalcitrance to therapy and longer duration. Given the anticipated surge in the use of hydroxychloroquine due to its reported benefits in those with coronavirus disease 2019, specific recognition of this entity is pivotal. We delineate it as generalized pustular figurate erythema.

Azithromycin and COVID-19: Prompt early use at first signs of this infection in adults and children, an approach worthy of consideration.

The devastating effects of the coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to urgent attempts to find effective therapeutic agents for inpatient and outpatient treatment of COVID-19. Initial enthusiasm for the combination of hydroxychloroquine and azithromycin has abated. However, as a result of positive clinical experience with azithromycin used alone during the first few days of the flu-like illness caused by this coronavirus, we recommend formal clinical trials using azithromycin early in the course of a COVID-19 infection. There is one clinical trial initiated, the individually randomized, telemedicine-based, "Azithromycin for COVID-19 Treatment in Outpatients Nationwide" based at the University of California San Francisco. This placebo-controlled trial is designed to determine the efficacy of a single 1.2-g dose of oral azithromycin to prevent COVID-19 patient progression to hospitalization. We recommend formal clinical trials of azithromycin in its prepackaged form at the first sign of COVID-19 infection in adults and children, using an initial adult dose of 500 mg followed by 250 mg per day for 4 days, a total cumulative dose of 1.5 g, and for children 5 to 18 years of age, 10 mg/kg on the first day followed by 5 mg/kg for 4 days.

Female pattern hair loss: A comprehensive review.

Female pattern hair loss is a common form of hair loss in women that increases in incidence with age. The etiology is unknown with numerous factors identified that influence its onset. Female pattern hair loss may be viewed as a marker for an increased risk of cardiovascular and metabolic disease. New treatments include microneedling, low-level laser therapy, and autologous fat transfer. This article focuses on the pathophysiology, diagnosis, systemic associations, and current treatments for female pattern hair loss, which is the most common cause of alopecia in women.

Localized sebaceous carcinoma treatment: Wide local excision verses Mohs micrographic surgery.

The optimal surgical management of sebaceous carcinoma (SC) has yet to be determined between Mohs micrographic surgery (MMS) and wide local excision (WLE). To investigate overall survival (OS) differences for SC undergoing WLE or MMS, The National Cancer Database (NCDB) was queried for all SC from 2004 to 2015 (n = 2863). Cases missing staging data, undergoing palliative care, showing lymph node extension, or of AJCC Stage III/IV were omitted. Chi-squared tests were used to analyze patient demographics, cancer characteristics, and treatment modalities. Kaplan-Meier and Cox proportional hazards regression modeling analyzed OS outcomes. A total of 554 cases met inclusion criteria (WLE [n = 243], MMS [n = 311]). Multivariate analysis revealed that cases treated in academic facilities (ref: non-acad; OR = 2.273; CI95% [1.448-3.568]; P < .001] were independently associated with greater MMS rates, whereas those with primaries on the trunk (ref: head/neck OR = 0.359; CI95%[0.203-0.634]; P < .001) and extremities (ref: head/neck OR = 0.399; CI95% [0.182-0.877]; P = .022) held lower MMS rates. Between surgical modalities, Kaplan-Meier survival showed no significant difference in outcomes (P = .611), with WLE and MMS demonstrating 5-year OS rates of 65.8% and 61.4%, respectively. On Cox proportional hazard regression, the survival outcomes of MMS and WLE did not show any significant differences in OS (HR = 0.832; CI95% [0.996-3.662]; P = .334). MMS and WLE of localized SC demonstrate similar overall survival outcomes. MMS may be preferred for margin control, tissue conservation, and cosmesis.

Gender differences in cutaneous melanoma: Demographics, prognostic factors, and survival outcomes.

Several recent studies have reported a considerably higher overall survival (OS) rate in females in various geographic regions This study further investigates the characteristics of melanoma that contribute to OS of women residing in the United States. Chi-square, Kaplan-Meier, and Cox regression models were used to analyze differences in demographics, treatment, and survival of invasive cutaneous melanoma in men and women diagnosed from 2004 to 2016 in the National cancer database. In 316 966 patients met inclusion criteria. Men had a significantly higher median age of diagnosis at 61 years (interquartile range or IQR: 51-72) in comparison to women where the median age of diagnosis was 55 years (IQR: 43-68) (P < .0001). The most common primary site for men was the trunk (35.5%), whereas the lower extremities were the most common primary site for women (30.3%). Women had a higher 5 year (82.6%) and 10 year (73.1%) OS compared to 5 year and 10 year OS of 72.2% and 58.7%, respectively, in men (P < .0001). When adjusting for confounders, female gender was independently associated with improved OS (ref: male HR = 0.791; 95% confidence interval 0.773-0.809; P < .0001). Overall, we conclude that female gender is an independent favorable prognostic factor for melanoma survival.

COVID-19 and immunosuppressive therapy in dermatology.

Coronavirus 2019 (COVID 19) was first detected in December 2019 in China. It has become a pandemic. With concern about therapies that may decrease immunity and enhance the severity of an individual's COVID-19 infection, leading to a possibly fatal outcome, use of immunosuppressants has become an important concern. This work focuses on management of various skin diseases individuals lacking immunity to COVID-19 but requiring a systemic immunosuppressant, keeping in view the challenge of the COVID 19 pandemic and that our knowledge of this virus and its effects on the immune system are incomplete including knowledge as to an individual's immunity after COVID-19 infection.