Yik Weng Yew

Bullous pemphigoid and its association with neurological diseases: a systematic review and meta-analysis.

Bullous pemphigoid (BP) is a chronic, autoimmune vesiculobullous disease that frequently occurs in the elderly population. Previous epidemiological studies have suggested an association between BP and neurological diseases; some studies, however, showed conflicting results. This study aimed to investigate if patients with BP have significantly higher risks for neurological disorders, compared to controls. A comprehensive search was performed using MEDLINE, EMBASE and Cochrane library databases. Case–control and cohort studies that assessed the relationship between BP and neurological diseases were included. DerSimonian and Laird random‐effects models were utilized to calculate the pooled relative risks (RRs). Publication bias was evaluated qualitatively by constructing a funnel plot and quantitatively by conducting Eggers test. Fourteen studies, with 23 369 BP cases and 128 697 controls were included in this meta‐analysis. Patients with BP were significantly more likely to have stroke (RR 2.68, 95% CI: 2.07–3.46), Parkinsons disease (PD; RR 3.42, 95% CI: 3.01–3.87), dementia (RR 4.46, 95% CI: 3.23–6.16), epilepsy (RR 2.98, 95% CI: 1.42–6.28), multiple sclerosis (RR 12.40, 95% CI: 6.64–23.17) and any aforementioned neurological disease (RR 4.93, 95% CI: 3.62–6.70), compared to controls. Moderate to high heterogeneity were observed for analyses of most neurological diseases, except for PD and multiple sclerosis. This study provided support for a significant association between BP and neurological diseases. Clinicians should be aware of this association and manage modifiable risk factors for neurological diseases accordingly.

An update of fixed drug eruptions in Singapore

Fixed drug eruptions (FDE) are most commonly caused by antibiotics and non‐steroidal anti‐inflammatory drugs (NSAIDs). The list of causative drugs changes with time and prescribing patterns but there has been no recent data on FDE seen in an outpatient setting in Singapore.

Itch in familial lichen amyloidosis: effective treatment with amitriptyline in two cases

Itch is a characteristic feature of lichen amyloidosis and the symptom can be debilitating. Treatments, however, are generally not effective. We report amitriptyline as a novel therapy in treating itch in two patients with familial lichen amyloidosis who did not respond to prior potent topical corticosteroids and antihistamines. Outcomes of treatment were assessed using the itch score on a visual analog scale, itch frequency, and the Dermatology Life Quality Index (DLQI). After taking amitriptyline 10 mg o.n. for 6 weeks, the itch score of one patient was reduced from 8.5 to 2 of 10, whereas the second patients itch score was reduced from 5 to 1. In the latter, his DLQI concurrently reduced from 14 to 6 of 30. Pathophysiology of itch in lichen amyloidosis may involve both cutaneous and neural components and amitriptyline is known to be useful for neuropathic itch. Low‐dose amitriptyline poses little risk of side effects and may offer an effective and safe alternative for the treatment of itch in familial cutaneous amyloidosis.

Understanding photodermatoses associated with defective DNA repair: Syndromes with cancer predisposition

Hereditary photodermatoses are a spectrum of rare photosensitive disorders that are often caused by genetic deficiency or malfunction of various components of the DNA repair pathway. This results clinically in extreme photosensitivity, with many syndromes exhibiting an increased risk of cutaneous malignancies. This review will focus specifically on the syndromes with malignant potential, including xeroderma pigmentosum, Bloom syndrome, and Rothmund-Thomson syndrome. The typical phenotypic findings of each disorder will be examined and contrasted, including noncutaneous identifiers to aid in diagnosis. The management of these patients will also be discussed. At this time, the mainstay of therapy remains strict photoprotection; however, genetic therapies are under investigation.

Complete remission of recalcitrant genital warts with a combination approach of surgical debulking and oral isotretinoin in a patient with systemic lupus erythematosus

Genital warts in immunocompromised patients can be extensive and recalcitrant to treatment. We report a case of recalcitrant genital warts in a female patient with systemic lupus erythematosus (SLE), who achieved complete remission with a combination approach of surgical debulking and oral isotretinoin at an initial dose of 20 mg/day with a gradual taper of dose over 8 months. She had previously been treated with a combination of topical imiquimod cream and regular fortnightly liquid nitrogen. Although there was partial response, there was no complete clearance. Her condition worsened after topical imiquimod cream was stopped because of her pregnancy. She underwent a combination approach of surgical debulking and oral isotretinoin after her delivery and achieved full clearance for more than 2 years duration. Oral isotretinoin, especially in the treatment of recalcitrant genital warts, is a valuable and feasible option when other more conventional treatment methods have failed or are not possible. It can be used alone or in combination with other local or physical treatment methods.

Understanding photodermatoses associated with defective DNA repair: Photosensitive syndromes without associated cancer predisposition

Photodermatoses associated with defective DNA repair are a group of photosensitive hereditary skin disorders. In this review, we focus on diseases and syndromes with defective nucleotide excision repair that are not accompanied by an increased risk of cutaneous malignancies despite having photosensitivity. Specifically, the gene mutations and transcription defects, epidemiology, and clinical features of Cockayne syndrome, cerebro-oculo-facial-skeletal syndrome, ultraviolet-sensitive syndrome, and trichothiodystrophy will be discussed. These conditions may also have other extracutaneous involvement affecting the neurologic system and growth and development. Rigorous photoprotection remains an important component of the management of these inherited DNA repair-deficiency photodermatoses.

Bullous pemphigoid and antecedent neurological diseases: An association with dementia

Background: Bullous pemphigoid is the most common subepidermal immunobullous disorder. Studies have reported the association between bullous pemphigoid and various neurological diseases. Aims: The aim of this study was to evaluate whether bullous pemphigoid is associated with pre-existent neurological diseases and whether specific diseases exhibit this association. Methods: All dermatology inpatients from January 2010 to May 2015 were analyzed. Bullous pemphigoid cases were identified based on clinical features and consistent histopathologic and direct immunofluorescence findings. Patients with other autoimmune bullous skin disorders were excluded. An equal number of inpatients with other skin conditions were selected randomly as age- and sex- matched controls. Results: Out of 3015 inpatients, 103 cases of bullous pemphigoid and 103 age- and sex-matched controls were included. Seventy six patients with bullous pemphigoid had a history of at least one neurological disease. After adjusting for age, gender, race, functional status and neuro-psychiatric medications, patients with bullous pemphigoid were found to be approximately thrice as likely to have a history of at least one neurological disease than were controls (odds ratio: 2.88; 95% confidence interval: 1.32–6.26; P = 0.008). Amongst the pre-existing neurological diseases, only dementia was statistically more prevalent in bullous pemphigoid cases compared to controls (adjusted odds ratio: 2.61; 95% confidence interval: 1.19–5.75; P = 0.017). Parkinson disease and psychiatric disorders demonstrated a higher adjusted risk among bullous pemphigoid patients but the difference was not statistically significant. Limitations: The limitations were potential referral and selection bias, as the patients were inpatients. There is a possible misclassification as the diagnosis of neurological diseases was performed using medical records. The duration from the diagnosis of neurological diseases to bullous pemphigoid could not be accurately determined as it was a retrospective review of records and most neurological diseases have a prolonged course. Conclusions: Pre-existent neurological disease, specifically dementia, was found to be associated with bullous pemphigoid.

A population-based cohort study of atopic eczema among young adult males in Singapore

Notalgia paresthetica: cryolipolysis as a novel potential treatment Notalgia paresthetica is a neurosensory condition, usually occurring on the upper back, which often presents with localized hyperpigmentation of the affected area with associated symptoms that may include one or more of the following: burning, coldness, hypoesthesia, increased pain, pruritus, and tingling. Although the clinical manifestations of this condition are well characterized, an effective pathogenesis-targeted treatment remains to be established. Pagliarello et al. provided a superlative and comprehensive study of the factors associated with the perceived severity, duration, side, and localization of notalgia paresthetica. Pagliarello et al. observed notalgia paresthetica to more frequently involve women, to be more severe in women, and to have longer disease duration in patients with higher body mass index. In addition, the researchers noted that the location of notalgia paresthetica was inversely related to the side that the patient slept on: specifically, it more commonly occurred on the right side of patients who slept on their left side and vis-a-verse. This latter observation prompted the investigators to suggest that the patient’s sleeping position could be a potential target for the management of notalgia paresthetica. Pagliarello et al. also emphasized that notalgia paresthetica is a sensory neuropathy; it occurs as a result of alteration of the cutaneous sensory nerves of the upper back. In addition, they were surprised to find that only four clinical studies had investigated this hypothesis of notalgia paresthetica pathogenesis in patients with the condition. Indeed, a treatment modality that addressed this aspect of the etiology of notalgia paresthetica might be therapeutically efficacious. I recently published an article hypothesizing the potential treatment of notalgia paresthetica that focuses on modification of the cutaneous nerves at the site of the symptoms: cryolipolysis. Cryolipolysis, a noninvasive procedure for subcutaneous fat layer reduction, has also been shown to not only cause a marked decrease in pain sensitivity but also a prolonged reduction in the density of both myelinated (to a greater extent because of their lipid-rich myelin sheath) and unmyelinated cutaneous nerves in the treated area. Hence, in addition to modification of patient’s sleep position, single or sequential cryolipolysis treatments – which target the suspected primary pathogenesis of notalgia paresthetica (the cutaneous sensory nerves) – may prove to be an effective treatment modality for this condition. Therefore, additional investigation into utilizing cryolipolysis for the management of notalgia paresthetica is warranted.

Pemphigus and nonassociation with antecedent neurological diseases: a case–control inpatient cohort

Pemphigus is an uncommon autoimmune blistering disorder characterized by the presence of IgG autoantibodies against desmosome adhesion molecules. Mortality rates are higher among Asians and those with more chronic conditions. There have been case reports and an uncontrolled study suggesting pemphigus to be associated with multiple sclerosis and Parkinson disease, respectively. The aim of this retrospective case–control study was, therefore, to investigate if pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are associated with preexisting neurological diseases, since the association between bullous pemphigoid, another autoimmune blistering disorder, and neurological diseases has been previously established. Our study population consisted of all inpatients referred to the dermatology service at Tan Tock Seng Hospital, Singapore, between January 1, 2010, and February 28, 2016. Cases had a confirmed diagnosis of pemphigus, with two out of three of these criteria: (i) typical clinical features of flaccid skin and/or mucosal blisters and/or erosions, (ii) consistent findings on histology or direct immunofluorescence, (iii) presence of antidesmoglein 1 and/or anti-desmoglein 3 autoantibodies. Agematched controls in a 21 ratio were randomly selected from inpatients with other dermatological conditions within the same period. Patients who had other autoimmune bullous subtypes (e.g., bullous pemphigoid, paraneoplastic pemphigus) and autoimmune connective tissue diseases (e.g., cutaneous lupus, dermatomyositis) were excluded. Diagnoses of neurological diseases were based on the International Classification of Diseases (ICD) diagnostic codes and were made by neurologists and/or geriatricians (for cases of dementia). Variables such as gender, race, activities of daily living, and extent of disease were included as confounding factors. A multivariate conditional logistic regression model was used to evaluate the association between pemphigus and a history of neurological diseases, such as dementia, stroke, Parkinson disease, and epilepsy. Sensitivity analysis with different logistic regression analysis models yielded similar results. Among 3468 inpatients, 36 cases of PV/PF and 72 matchedcontrols were included (Table 1). Their mean age was 54.9 years, and there was a slight male predominance (64.8%). Chinese (61.1%) formed the largest majority. Our cohort comprises a higher percentage of Malays (31.8%) compared to Singapore’s general population (13.3%). The majority of the patients were functionally independent (96.2%). These characteristics were not significantly different between cases and controls. Among the cases, four had a history of at least one neurological disease. After adjusting for the various Table 2 Univariate and multivariate conditional logistic regression model of neurological diseases with agematched pemphigus cases and controls

Scrotal cutaneous chylous reflux: a scrotum with a white coat

Cutaneous chylous reflux (CCR) is a rare condition with few cases reported worldwide. It can be attributed to primary congenital lymphangiectasia or secondary lymphatic disruption by malignancy, trauma, inflammation, or previous surgery. Cutaneous presentation is variable and depends on the site involved, acuity of presentation, and rapidity of reflux. Cases involving chylous ascites, chylothorax, chyluria, and chylopericardium have been reported. Slow forming chylous papules or vesicles resemble xanthomas. The term weeping scrotum has been coined for scrotal CCR since the 1970s. We report a case of scrotal CCR presenting in an elderly Asian man with non-small cell lung carcinoma. An 82-year-old Chinese man presented with a 6-month history of a macerated plaque over the right scrotum. White exudates were noted over the scrotal surface (Fig. 1). No topical medications were used previously. Past medical history was significant for right upper lung non-small cell lung carcinoma with distant metastases to the liver, brain, and bone diagnosed one year ago. He has since received chemoradiotherapy. Skin biopsy showed features of dilated thin-walled vessels lined by endothelial cells with focal hobnailing and containing eosinophilic fluid with few red blood cells, consistent with lymphangioma (Fig. 2). Fluid analysis of the milky scrotal exudate showed an elevated triglyceride level of 3.08 mmol/L. Although the patient declined further lymphatic imaging to determine the anatomy and function of the lymphatic system, the collation of results was likely in keeping with scrotal CCR. It is postulated that lymphatic channels may have been obstructed by tumor or radiation effects, resulting in chylous reflux. Poor prognosis from the metastatic lung carcinoma and premorbid state precluded him for surgical lymphatic correction. He was subsequently managed in a hospice. There are few cases of CCR reported worldwide. No age or comorbidity predilection has been identified. Huang et al 6 reported a case in a 17-year-old healthy male. Laboratory findings were similar to our current case presentation. Vesicles on the patient’s scrotum were noted to have active discharge, worse on prolonged standing. Saccular dilatations of lymphatic vessels were noted on histology. The patient was managed conservatively. Suehiro et al. reported another case of a 25-year-old man with swelling of the right lower limb and lymphangiectasia demonstrated on lymphangioscintigraphy. The patient, however, did not respond well to conservative treatment and eventually underwent lymphaticovenous anastomoses in the ankle and groin. Diagnosis of chylous effusion is confirmed by two or more of the following evaluations: the appearance of milky fluid, a triglyceride level of more than 1.24 mmol/L, and lipoprotein analysis for the presence of chylomicrons. In a patient with CCR, secondary causes of lymphatic obstruction and reflux should be sought. Complications of chronic chylous leak such as anemia, malnutrition,