Treatment options for leishmaniasis.

Leishmaniasis is broadly classified into three types: cutaneous, mucocutaneous and visceral. The visceral form is most dangerous and can result in death. Although leishmaniasis is an ancient disease, its treatment is still challenging. Several drugs, differing in their cost, toxicity, treatment duration and emergence of drug resistance, are used for different types of leishmaniasis. To overcome these limitations, the search for newer drugs and other treatments continues. In this article, we discuss conventional drugs, other treatments, including newer options such as immunotherapy and immunochemotherapy, and future prospects for leishmaniasis treatment.

Prolonged overall survival following metastasectomy in stage IV melanoma.

BACKGROUND/OBJECTIVES: Current literature supports mixed conclusions regarding the outcomes of metastasectomy in Stage IV melanoma. The objective of this national study was to determine the associations of non-primary site surgery with overall survival (OS) in Stage IV melanoma. METHODS: The National Cancer Database (NCDB) was queried for all Stage IV melanoma cases diagnosed from 2004 to 2015. Cases missing treatment/staging data or undergoing palliative treatment were excluded (remaining n = 14 034). Patients were separated into 'metastasectomy' (n = 4214, 30.0%) and 'non-metastasectomy' (n = 9820, 70.0%) cohorts. Survival outcomes were analysed using Kaplan-Meier and Cox proportional hazards regressions. RESULTS: On univariate analysis, patients with Stage IV melanoma undergoing metastasectomy (median survival: 15.67 month) had greater overall survival compared with those not receiving non-primary surgery (median survival: 7.13 month; 5-year OS 13.2% vs. 5.6%, P < 0.001). M1a patients that underwent non-primary metastasectomy (median survival: 46.36 month) showed greater survival than those that did not (median survival: 15.31 month; P < 0.001). Metastasectomy was undertaken more frequently for cutaneous (M1a) metastasis compared with non-M1a metastasis (34.6% vs. 28.4%, P < 0.001). Of those receiving metastasectomy, 20.3% also received primary site resection, 33.6% radiation, 26.5% chemotherapy and 31.5% immunotherapy. Controlling for covariates on Cox proportional hazard analysis, all metastasectomy patients demonstrated longer survival [Hazard Ratio = 0.519, P < 0.001; CI 95% (0.495-0.545)] as well as when analysing solely M1a metastasectomy patients [Hazard Ratio = 0.546, P < 0.001; CI 95% (0.456-0.653)], lung (M1b) metastasectomy patients [Hazard Ratio = 0.389, P < 0.001; CI 95% (0.328-0.462)] and visceral (M1c) metastasectomy patients [Hazard Ratio = 0.474, P < 0.001; CI 95% (0.434-0.517)]. CONCLUSION: Metastasectomy for Stage IV melanoma is independently associated with improved OS in metastatic cases involving the skin, lung and visceral organs.

Generalized pustular psoriasis: a review and update on treatment.

Generalized pustular psoriasis (GPP) is a subtype of pustular psoriasis characterized by painful and occasionally disfiguring cutaneous manifestations with sepsis-like systemic symptoms. Affecting any age and race, GPP can occur with other forms of psoriasis or by itself. Stimuli for flares include medications, infections and environmental triggers. The interleukin family and caspase recruitment domain family have been implicated in its pathogenesis. Other forms of pustular psoriasis include impetigo herpetiformis, palmoplantar pustular psoriasis, annular pustular psoriasis and acrodermatitis continua of Hallopeau. Treatment is not well established, but includes the use of retinoids, methotrexate, cyclosporine, corticosteroids, TNF-alpha inhibitors, topical therapy and phototherapy. The use of TNF-alpha inhibitors may result in the formation of antidrug antibodies and should be administered with methotrexate.

Milker's nodule: an occupational infection and threat to the immunocompromised.

Milker's nodule virus, also called paravaccinia virus, is a DNA virus of the parapoxvirus genus transmitted from infected cows to humans. It results from contact with cattle, cattle by-products or fomites. Classified as an occupational disorder, those at risk of exposure include farmers, butchers and agricultural tourists. The viral infection begins 5-15 days after inoculation as an erythematous-purple, round nodule with a clear depressed centre and a surrounding erythematous ring. While familiar to those in farming communities, the presence of the nodule may be concerning to others, particularly the immunosuppressed. Milker's nodules are self-limited in immunocompetent individuals and heal without scarring within 8 weeks. Another member of the Parapoxvirus genus, the orf virus, is also transmitted from animals to humans by direct contact. While complications are rare, haematopoietic stem cell transplant recipients are at risk of graft-versus-host disease, as the parapoxvirus may trigger these complications in immunocompromised individuals. In addition, paravaccinia may serve as the antigen source for the development of erythema multiforme. The unique structure and replication process of viruses in the Poxvirus family, while includes the Parapoxvirus genus, have been a focus for treatment of infections and cancer. Manipulation of these viruses has demonstrated promising therapeutic possibilities as vectors for vaccines and oncologic therapy.

Topical antiviral and antifungal medications in pregnancy: a review of safety profiles.

Medications should be employed with caution in women of childbearing age who are pregnant or considering pregnancy. Compared to oral or parenteral agents, topical medications have limited systemic absorption and are deemed safer. However, their safety profile must be assessed cautiously due to the limited available data. In this article, we aggregate human and animal studies to provide recommendations on utilizing topical antiviral and antifungal medications in pregnancy. For antiviral medications, acyclovir and trichloroacetic acid are safe to use in pregnancy. Docosanol, imiquimod and penciclovir are likely safe, but should be utilized as second-line agents. Podofilox and podophyllin resin should be avoided. For antifungal medications, clotrimazole, miconazole and nystatin are considered first-line agents. Butenafine, ciclopirox, naftifine, oxiconazole and terbinafine may be utilized after the above agents. Econazole should be avoided during the first trimester and used sparingly during 2nd and 3rd trimester. Ketoconazole and selenium sulphide are likely safe, but should be employed in limited areas for brief periods.

Vitiligo and depression: a systematic review and meta-analysis of observational studies.

Vitiligo is a common depigmenting disorder with profound psychosocial impacts. Previous observational studies have suggested a link between vitiligo and psychiatric morbidity, such as depression. However, variability in study design makes it difficult to quantify accurately the relationship between vitiligo and depression. We aimed to investigate the underlying prevalence and risk of depression among patients with vitiligo. A comprehensive search of MEDLINE, Embase and the Cochrane Library was conducted. Cross-sectional, case-control or cohort studies that assessed the prevalence of depression among patients with vitiligo or the relationship between vitiligo and depression were included. DerSimonian and Laird random-effects models were utilized to calculate the pooled prevalence and relative risks. Publication bias was evaluated by funnel plots and Egger's tests. Twenty-five studies with 2708 cases of vitiligo were included. Based on diagnostic codes, the pooled prevalence of depression among patients with vitiligo was 0·253 [95% confidence interval (CI) 0·16-0·34; P < 0·001)]. Using self-reported questionnaires, the pooled prevalence of depressive symptoms was 0·336 (95% CI 0·25-0·42; P < 0·001). The pooled odds ratio of depression among patients with vitiligo was 5·05 vs. controls (95% CI 2·21-11·51; P < 0·001). Moderate-to-high heterogeneity was observed between the studies. Patients with vitiligo were significantly more likely to suffer from depression. Clinical depression or depressive symptoms can be prevalent, with the actual prevalence differing depending on screening instruments or, possibly, geographical regions. Clinicians should actively evaluate patients with vitiligo for signs/symptoms of depression and provide appropriate referrals to manage their psychiatric symptoms accordingly.

Glucagonoma syndrome: a review and update on treatment.

Glucagonoma syndrome is defined by the presence of an alpha-cell secreting tumour of the pancreas, elevated levels of glucagon, and a characteristic rash called necrolytic migratory erythema (NME). NME is usually a specific and often initial finding of glucagonoma syndrome, but it may occur in other settings unassociated with an alpha-cell pancreatic tumour (pseudoglucagonoma syndrome). Glucagonoma syndrome must be distinguished from pseudoglucagonoma syndrome. Prompt recognition of NME and subsequent workup for a glucagonoma can allow for an earlier diagnosis and enhance the chances of a favourable outcome. In particular, metastases occur late, so early recognition of glucagonoma syndrome before liver metastases can be life-saving. Surgical resection is the definitive treatment for glucagonoma syndrome, although chemotherapeutic agents, somatostatin analogues and radionuclide therapy are also employed. Herein, we offer an approach to workup after identifying NME and an update on its current treatment modalities.

Basal cell naevus syndrome: an update on genetics and treatment.

Basal cell naevus syndrome is an autosomal dominant disorder that stems from mutations in multiple genes, most commonly patched 1 (PTCH1). The classic triad of symptoms consists of basal cell carcinomas, jaw keratocysts and cerebral calcifications, although there are many other systemic manifestations. Because of the broad range of symptoms and development of several types of tumours, early diagnosis and close monitoring are essential to preserve quality of life. Targeting treatment is often difficult because of tumour prevalence. Newer inhibitors of the hedgehog signalling pathway and proteins involved in proliferative growth have shown therapeutic promise. In addition, preventive medications are being devised. We propose a method for determining appropriate treatment for cutaneous tumours.

Systemic effects of treatment with mTOR inhibitors in tuberous sclerosis complex: a comprehensive review.

Tuberous sclerosis complex (TSC) is a genetic multisystem disorder associated with constitutive overactivation of the mammalian target of rapamycin (mTOR) pathway and characterized by development of benign tumours in various organs. mTOR inhibitors have proven to be effective in the targeted therapy of certain TSC-associated pathologies such as subependymal giant cell astrocytomas (SEGAs) and renal angiomyolipomas (AMLs). Accumulating experimental and clinical data suggest that mTOR inhibitors might have a systemic, disease-modifying influence on affected individuals. This systematic review provides an analysis of available clinical data concerning systemic effect of mTOR inhibitors and the influence of mTOR inhibition on different manifestations of TSC in individual patients.

Neonatal leukaemia cutis.

Neonatal leukaemia cutis is a significant neoplasm that may represent a cutaneous manifestation of systemic leukaemia, usually of myeloblastic type. Rarely, it may be or appear to be limited to skin, in which case it is called neonatal aleukaemic leukaemia cutis. By definition, it presents within the first 4 weeks of life and often has a 'blueberry muffin baby' appearance of magenta coloured nodules affecting almost any area of the skin, usually sparing mucous membranes, palms and soles. This clinical pattern is more commonly associated with neonatal infections such rubella and toxoplasmosis, and may be evident with other neonatal neoplasms such as neuroblastoma. Due to the morbidity associated with chemotherapy and reported cases of spontaneous remission without systemic progression in those with neonatal aleukaemic leukaemia cutis without 11q23 translocation, the authors not treating the child with chemotherapy, but to simply monitor for fading of the violaceous nodules, and watch for possible signs of systemic leukaemia.

Infectious eczematoid dermatitis: a comprehensive review.

Infectious eczematoid dermatitis (IED) is characterized by an acute eczematous eruption triggered by purulent discharge from a primary infected site. Alcohol consumption, cigarette smoking and occupations with higher incidences of contact dermatitis portend increased risk for IED. Staphylococcus aureus is the most commonly cultured microbe from affected skin, with Streptococcus species the second most. Patients are first evident with peripherally spreading vesicles and pustules radiating from an infected site. Older areas of involvement become crusty, scaly and erythematous. Diagnosis is clinical. Other eczematous rashes, including autoeczemitization and contact dermatitis, should be on the differential diagnosis list. The treatment centres on topical antibiotics and soaks. Prognosis has improved since the advent of antibiotics. However, cases with multiple relapses and poor response to therapy are still observed.

Pseudofolliculitis cutis: a vexing disorder of hair growth.

Pseudofolliculitis cutis (PFC) is a troublesome and potentially disfiguring cutaneous disorder characterized by a chronic inflammatory response to ingrown hair. Despite a simple precipitating stimulus, ingrown hair, PFC has a relatively complex aetiology that can involve grooming practices, hair type, genetic predisposition and medication history. Curly hair and a single-nucleotide substitution in the gene encoding keratin 75 may act synergistically to increase the risk for developing this condition. PFC is most common in men of sub-Saharan African lineage, but can occur in men and women of many different ethnicities, particularly in body areas where hair is coarse, abundant and subject to traumatic removal. Treatment options for PFC can be divided into three main categories: modifying hair removal practices, managing symptoms with medication, and long-term hair removal with laser therapy. Laser hair removal is safe and effective in most skin types and has become increasingly popular among dermatologists in the treatment of PFC. However, it is imperative that the laser system and parameters are specifically matched to the patient's skin type.

Body dysmorphic disorder: beyond skin deep.

Body dysmorphic disorder (BDD) is a psychiatric illness that primarily affects adolescents and young adults of both sexes. Patients have a distorted self-image, which manifests as a preoccupation with slight or imagined defects in the face, nose, skin, hair or any part of the body that ultimately interferes with daily functioning. It is a relatively common yet long unrecognized problem. Patients often seek multiple physician assessments for their perceived defects and request cosmetic procedures. Early intervention can prevent a cycle of multiple surgeries, as the outcome is usually poor and may lead to exacerbation of symptoms, anger and litigation. BDD is a disabling, and even life-threatening, condition; it can lead to major depression and suicidal ideation. Selective serotonin reuptake inhibitors and cognitive behavioral therapy are the mainstay of treatment and are beneficial in most patients. A multidisciplinary approach is strongly recommended.