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.

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.

Efficacy of iontophoresis with glycopyrronium bromide for treatment of primary palmar hyperhidrosis.

BACKGROUND: There is limited data on the efficacy of iontophoretic treatment of primary palmar hyperhidrosis using glycopyrronium bromide. The first line treatment for primary palmar hyperhidrosis is usually topical aluminium chloride, but clinical experience indicates that it is not effective for more severe disease. OBJECTIVE: To evaluate the efficacy of using glycopyrronium bromide iontophoresis in the treatment of primary palmar hyperhidrosis, and to evaluate if the benefit of treatment varies with the severity of disease. METHODS: This is an open-label study involving patients undergoing weekly treatment of iontophoresis with glycopyrronium bromide for 4 weeks. Gravimetric measurements of sweat production and subjective scores of palmar sweatiness were recorded prior to starting treatment and 1 week after the last treatment. Side-effects were monitored weekly. RESULTS: Twenty two of the 25 patients recruited completed the 4-week treatment. There was a significant mean improvement of 23.4 mg/min (P = 0.001) between baseline and post-treatment gravimetric measurements. Patients with a higher baseline sweat output demonstrated a trend towards a greater reduction in sweat production (Pearson's correlation correlation coefficient, r = 0.41). The patients experienced dryness of the palms for a mean duration of 5 days after iontophoresis. All patients reported an improvement in satisfaction scores and 81.8% reported an improvement in subjective severity scores. No serious side-effects were encountered during the study. CONCLUSIONS: Iontophoresis using glycopyrronium bromide is an effective and well-tolerated treatment for primary palmar hyperhidrosis. The possibility of its greater benefit in patients with more severe baseline disease requires verification.

Targeted treatment of pruritus: a look into the future.

Recent advances in pruritus research have elucidated mediators and neuronal pathways involved in itch transmission, and this fast emerging knowledge may possibly be translated into new therapies in the near future. In the skin and peripheral nerves, potential mediator and receptor therapeutic targets include the H4 histamine receptor, protease-activated receptor 2, serine proteases, cathepsin S, peripheral mu- and kappa-opioid receptors, interleukin-31, transient receptor potential vanilloid 1 and 3, fatty acid amide hydrolase, nerve growth factor and its receptor, acetylcholine, and the Mas-related G protein-coupled receptors. In the spinal cord, gastrin-related peptide and its receptor, as well as substance P and its receptor neurokinin receptor-1 serve as potential therapeutic targets. In the brain, reduction of itch perception and modulation of emotions may possibly be achieved through drugs acting on the anterior cingulate cortex. Clinically, management of pruritus should be instituted early and should address the skin pathology, peripheral neuropathy, central sensitization, and the cognito-affective aspects of the disease.

Systemic lupus erythematosus presenting as Stevens-Johnson syndrome and toxic epidermal necrolysis: a report of three cases.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening dermatological conditions that are characterized by mucositis, epidermal detachment and erosions. The underlying etiology in SJS and TEN is almost invariably secondary to drugs. Rarely, other causes such as systemic lupus erythematosus (SLE), infections and vaccinations have been implicated. This report describes three patients with SLE who presented with manifestations of SJS/TEN without a clear drug causality. All three patients presented with photodistributed macular exanthema, which evolved to target lesions, bullae, erosions or sheet-like detachment. This was associated with oral mucositis and conjunctivitis. The onset of the rash was insidious with a protracted clinical course. Ultraviolet exposure and steroid tapering appear to be precipitating factors. In two of the patients, SJS and TEN were the initial presentation of lupus. Although SJS and TEN are almost invariably due to medications, they may, rarely, be an initial presentation of lupus, particularly when associated with an initial photodistribution, absence of genital involvement and a prolonged clinical course.

Approach to hypopigmentation disorders in adults.

Acquired hypopigmentation disorders in adults can be classified on the basis of lesion extent, and can generally be divided into disorders with localized, widespread or generalized lesions. Clinical findings, comprising the degree of pigment loss (hypopigmentation and depigmentation) and associated morphological findings (e.g. epidermal changes, infiltration and induration), are used to further distinguish the disorders. Diagnosing the disorders is important because the underlying causes may be treatable and some of the disorders are associated with malignancies. A systemic approach is useful for this clinical condition, as the causes are heterogeneous and investigations are usually nondiagnostic.

A randomized double-blind controlled trial to compare a triclosan-containing emollient with vehicle for the treatment of atopic dermatitis.

The use of topical antiseptics in the treatment of atopic dermatitis (AD) has previously been explored. However, no triclosan-containing leave-on emollient has been evaluated previously, to our knowledge. The aims of this study were to assess the safety and efficacy of an emollient containing triclosan compared with the emollient alone (vehicle) for the treatment of AD. Eligible patients with mild to moderate AD were randomized to receive either the study cream or vehicle. All patients also received a low-potency corticosteroid cream to use during the treatment phase of the study if necessary. Patients were assessed for severity according to the SCORing Atopic Dermatitis (SCORAD) Index, amount of corticosteroid used, patient assessment of cream, and adverse events (AEs). In total, 60 patients received either the study cream or vehicle, and an intention-to-treat analysis was performed. At day 14, there was a significant decrease in SCORAD from baseline for the study cream compared with vehicle (P < 0.05). At day 27, although there was an improved mean reduction from baseline, this was no longer significant (P > 0.05). Only four patients had mild treatment-related AEs. The mean total amount of topical steroid applied by the patients using the study was significantly lower than that used by controls (P = 0.40). Triclosan-containing leave-on emollient was safe and highly acceptable to patients. However, the overall benefit on day 27 was not significant. Nevertheless, the amount of topical steroid used by patients was significantly less with the study cream than with the vehicle, thus further studies are needed to confirm its steroid-sparing effect.