Topical calcineurin inhibitors in eczema and cancer association: A cohort study.

INTRODUCTION: Cancer risk associated with topical calcineurin inhibitors (TCIs) remains unclear. OBJECTIVE: To evaluate the association between TCIs and cancer among patients with atopic and endogenous eczema. METHODS: Incident cancers were identified from the National Cancer Registry. Data were analyzed using the Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals. RESULTS: 880 unique cases of cancer developed in 66 176 patients from 2004 to 2012. The adjusted HRs for overall malignancy were 0.82 (95%CI 0.44-1.39) for tacrolimus-exposed and 1.30 (95%CI 0.59-2.45) for pimecrolimus-exposed. The only significant cancer association observed was lymphoid leukemia among the tacrolimus-exposed: HR 7.58 (95%CI 1.64-25.8). All affected patients had young-onset B-cell leukemia. Subgroup analysis of pediatric patients (≤16 years) showed significant association between tacrolimus use and B-cell leukemia: HR 26.4 (95%CI 4.77-146). CONCLUSIONS: In this first Asian study on the risk of TCIs and malignancies, we do not find an association between use of tacrolimus and pimecrolimus in atopic and endogenous eczema and the overall development of malignancies. However, the use of topical tacrolimus was found to be associated with the development of B-cell acute lymphoid leukemia in pediatric eczema patients; further studies are required to investigate if a true association indeed occurs.

Pathophysiology of pruritus in primary localized cutaneous amyloidosis.

BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) is a chronic pruritic dermatosis prevalent among Southern Chinese and South American populations. Pruritus is frequently present and can be debilitating; its pathophysiology is largely unknown. OBJECTIVES: To investigate if small-fibre neuropathy (SFN), which results in a reduction of intraepidermal nerve fibres (IENF) and abnormalities in quantitative thermal sensory testing (QST), is present in PLCA. METHODS: Twenty Chinese patients (10 men) and 20 ethnicity-, sex- and age-matched controls underwent QST assessments. The patients' warm detection threshold (WDT) and heat pain threshold at the typical lesional sites were determined. Serum interleukin (IL)-31 levels were measured. Lesional biopsies were stained for IENF, IL-31 and its receptor's subunits [IL-31RA and oncostatin M receptor-ß (OSMRß)], and nerve growth factor (NGF) and its receptor [tropomyosin receptor kinase A (TrkA)], and were compared with normal skin obtained from archival paraffin-embedded specimens. RESULTS: WDT was significantly higher in patients at all sites and correlated with itch scores (r = 0·59; P < 0·01). Patient biopsies revealed lower IENF counts (P < 0·01 using protein gene product 9.5, ß3-tubulin and Neurofilament 200 stains) and increased epidermal expression of OSMRß (P < 0·01) and IL-31RA (P < 0·01). Cutaneous IL-31, NGF and TrkA stains were not significantly increased in patients. Serum IL-31 was not significantly higher in patients. CONCLUSIONS: SFN is present in PLCA. Pruritus in PLCA is likely associated with hypersensitivity of cutaneous nerve fibres, which may be related to an increased expression of epidermal IL-31 receptors. Targeting IL-31 receptors is therefore a potential therapeutic approach.

Application of iodinated starch powder using an atomizer spray gun - a new and effective tool to evaluate hypohidrosis.

BACKGROUND: Hypohidrosis is defined as diminished sweating in response to an appropriate thermal or sympathetic stimulus. When encountered in a clinical setting, it necessitates an accurate documentation of its pattern and extent to prognosticate the risk of associated heat-related illnesses. This can be achieved by thermoregulatory sweat testing which includes a starch-iodine sweat test that can be administered via various methods. OBJECTIVE: To describe and evaluate the effectiveness and safety of a novel method of using an atomizer spray gun in administering the starch-iodine test. METHODS: We describe the administration of the starch-iodine test via an atomizer spray gun (Series 700 Lab Model; Mitsuba Systems, Mumbai, India). The method was utilized for the evaluation of 30 individuals who presented with symptoms of hypohidrosis. RESULTS: Application of iodinated starch powder prepared in-house with the atomizer spray gun achieved a lightweight and homogeneous coat on our patients' skin which allowed for clear visualization of the sweating pattern in areas of anhidrosis. The sharp demarcation of the pathological regions enabled the precise calculation of the affected body surface area of impaired sweating. Unlike the starch-iodine tests using the Minor and Wada methods, neither staining of the skin nor irritation was detected in this method. CONCLUSION: We report a novel method of using an atomizer spray gun to perform the starch-iodine test in a rapid, reproducible, effective, and safe manner suitable for use in the clinical evaluation of hypohidrosis.

Primary localized cutaneous amyloidosis: association with atopic dermatitis.

BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) is a chronic pruritic dermatological disorder of unknown aetiology. Genetic mutations in cases of familial PLCA have been mapped to the oncostatin-M receptor (OSMR) ß, a subunit of interleukin (IL)-31 receptor. IL-31 has been implicated in the pathogenesis of atopic dermatitis (AD). OBJECTIVES: To assess if AD is more prevalent in patients with PLCA compared to patients with other conditions attending the same dermatology clinic. Secondarily, to investigate if the prevalence of AD, severity of itch, morphology and locations of PLCA differ between familial and sporadic forms. METHODS: Consecutive patients with the clinical diagnosis of PLCA visiting a dermatology clinic were evaluated by a single investigator. Data on demographics, family history, morphological types and locations of PLCA, and itch score were collected and they were screened for concomitant AD based on history and physical examination. The control population consisted of consecutive patients with diagnoses other than PLCA seen in the same clinic. RESULTS: A total of 44 patients with and 97 controls were evaluated. The prevalence of AD in patients with PLCA was significantly higher than in controls, at 75% and 39.2% respectively (OR = 4.66, 95% CI = 2.10 to 10.3, p < 0.0005). The prevalence of AD in sporadic cases was significantly higher than familial cases, at 84.4% and 50% respectively (OR = 5.4, 95% CI = 1.23 to 23.7). Mean itch levels, morphological types and locations of PLCA did not differ between familial and sporadic cases. CONCLUSIONS: AD was associated with PLCA and the association was stronger with the sporadic compared to the familial cases.

Treatment of acne vulgaris during pregnancy and lactation.

Acne vulgaris is a common problem encountered by pregnant and lactating women. Unfortunately, in clinical practice, treatment is often not optimized as a result of the lack of safety data and unified recommendations on the use of the various anti-acne therapies. In this narrative review, current data on their safety is summarized. We recommend the use of topical medications as first-line treatment for acne vulgaris in pregnant and lactating women. These include antibiotics (erythromycin, clindamycin, metronidazole and dapsone), benzoyl peroxide, azelaic acid and salicylic acid. Oral agents and/or light-based therapy may be considered as second-line treatment. The former consists of oral macrolides (erythromycin and azithromycin), cephalexin or zinc compounds. Blue-violet or red light phototherapy may be used as monotherapy or in addition to topical and/or oral therapies. Hormonal therapy, antibiotics consisting of tetracyclines, co-trimoxazole and fluoroquinolones, and both oral and topical retinoids should be avoided.

Approach to hypohidrosis.

Hypohidrosis refers to diminished sweating in response to appropriate stimuli. This can cause hyperthermia, heat exhaustion and death. The aetiology of hypohidrosis can be divided into exogenous, dermatological and neurological causes. Exogenous causes act either by systemic neurohormonal inhibition of sweating or localised damage to the skin and sweat glands. Dermatological disorders can result from congenital disorders, wherein other ectodermal tissues may also be affected, or acquired disorders in which manifestations of the primary disease predominate. Neurological disorders should be classified based on an upper motor neuron or lower motor neuron pattern of disease. In the former, there is spasticity and hyperactive reflexes whereas in the latter, flaccidity and hypoactive reflexes predominate. Acquired idiopathic generalised anhidrois refers to isolated anhidrosis with no other detectable abnormalities. When approaching a patient with hypohidrois, exogenous causes should first be excluded. Physical examination, paying attention to mucocutaneous manifestations and neurological signs, will dichotomise if the lesion is dermatological or neurological. In the former, a skin biopsy is the investigation of choice. In the latter, one should consider magnetic resonance imaging of the brain and spinal cord for upper motor neuron lesions, nerve conduction tests for lower motor neuron lesions and autonomic nerve function tests for autonomic dysfunction. Finally, if a diagnosis of acquired idiopathic generalised anhidrosis is suspected, a quantitative sudomotor axon reflex test and serum immunoglobulin-E levels may be performed. Treatment involves addressing the underlying condition and avoidance of aggravating factors. Acquired idiopathic generalised anhidrosis responds well to high dose systemic corticosteroids.