Efficacy and Safety of Botulinum Toxin B in Focal Hyperhidrosis: A Narrative Review.

Botulinum toxin type B (BoNT-B), known as Myobloc® in the United States and as Neurobloc® in Europe, is a new therapeutically available serotype among the botulinum toxin family. During the last years several data have been reported in literature investigating its efficacy and safety, as well as defining the dosing and application regiments of BoNT-B in the treatment of hyperhidrosis. Moreover, recent studies have been examining its safety profile, which may be different from those known about BoNT-A. The aim of this review is to provide information about what is currently known about BoNT-B in regards to the treatment of focal hyperhidrosis.

Botulinum Toxin Type A for Treatment of Forehead Hyperhidrosis: Multicenter Clinical Experience and Review from Literature.

Among the forms of idiopathic hyperhidrosis, those involving the forehead have the greatest impact on patients' quality of life, as symptoms are not very controllable and are difficult to mask for patients. Although the local injection therapy with Incobotulinum toxin type A (IncoBTX-A therapy) can be considered a rational treatment, data from the literature describing both efficacy and safety of the treatment over the long term are poor. The aim of this report is to describe the single-center experience of five patients seeking treatment, for forehead hyperhidrosis with IncoBTX-A. To evaluate the benefits, safety profile and duration of anhidrosis, patients were treated following a standardized procedure and then followed until clinical relapse. The amount of sweating was measured by gravimetric testing, the extension of hyperhidrosis area was measured through Minor's iodine starch test, and response to the treatment was evaluated using the Hyperhidrosis Disease Severity Scale (HDSS) and the Dermatology Life Quality Index (DLQI). In all treated patients, a significant anhidrotic effect was observed 4 weeks after the treatment and lasted for approximately 36 weeks. The reduction in sweat production was associated with significant amelioration of symptoms and quality of life for all treated patients. No serious side effects occurred; one patient complained of a mild transient bilateral ptosis. Although further wider studies are required, our preliminary results seem to encourage the use of IncoBTX-A in forehead hyperhidrosis.

Effects of in vivo application of an overnight patch containing Allium cepa, allantoin, and pentaglycan on hypertrophic scars and keloids: Clinical, videocapillaroscopic, and ultrasonographic study.

Several therapeutic approaches have been described for their treatment of hypertrophic scars and keloids, but to date, the optimal treatment has not been established yet. Our in vivo study was conducted to evaluate the effect of a medical device consisting in an adhesive patch containing onion extract (Allium cepa) 10%, allantoin 1%, and pentaglycan 4% (Kaloidon patch) on hypertrophic scars and keloids. Thirty-nine patients with hypertrophic scars and seven patients with keloids were asked to apply an adhesive patch containing Allium cepa, allantoin, and pentaglycan once/day for at least 8 h consecutively, for 24 weeks. Patients were reevaluated 6 weeks (T6), 12 weeks (T12), and 24 weeks (T24) after starting the treatment through POSAS scale v 2.0, ultrasonographic, and videocapillaroscopic assessment. The investigated medical device was able to induce a significant improvement of POSAS starting from T12, with a positive amelioration trend until T24. However the patient-assessed POSAS sub-items showed improvement already after 6 weeks, whereas a significant improvement of the observer-assessed POSAS sub-items was observed only after 12 weeks (P < .001). Ultrasonography and intravital videocapillaroscopy confirmed a significant improvement of skin scars thickness (P < .001) and vascularization (P < .001) after 12 weeks of medical device application at least, with increasing improvement until T24. Applying an adhesive patch containing Allium cepa, allantoin, and pentaglycan once a day for at least 8 consecutive hours seems to be able to improve the clinical and morphological characteristics of the scars of the skin in 24 weeks.

Analysis of neoplastic skin complications in transplant patients: experience of an Italian multidisciplinary transplant unit.

BACKGROUND: Transplant patients need to be strictly followed, since the immunosuppressive therapies they usually receive can increase the risk of skin complications. This study aims to evaluate the prevalence of neoplastic skin complications in transplant patients. METHODS: We analyzed 256 liver or kidney transplant patients. The follow-up mean period was 7±3.5 years. It was also evaluated the prevalence of cutaneous neoplastic complications according to the immunosuppressive regimen received by patients as follows: cyclosporine, tacrolimus, steroids, mycophenolate mofetil or everolimus, in single, double or triple therapy. RESULTS: The 18.36% of patients developed neoplastic complications, among these 9.37% actinic keratoses, 8.20% non-melanoma skin cancer, and 0.78% cutaneous melanoma. Among patients who developed non melanoma skin cancer, 61.90% had basal cell carcinoma, 23.81% squamous cell carcinoma, 52% Kaposi's sarcoma and 4.76%, Malherbe's epithelioma. CONCLUSIONS: This study demonstrated the increased risk of skin cancer in transplant patients during the first 7 years of follow-up and made the dermatologists aware about the need of a regular cutaneous follow-up for this subset of patients.

Lifelong widespread warts associated with human papillomavirus type 70/85: a new diagnostic entity?

We present a patient with HPV 70/85-positive widespread cutaneous warts characterized by clinical and histological features atypical for classic generalized verrucosis or epidermodysplasia verruciformis. The cutaneous HPV infection is characterized by verrucous papules or plaques variable in size, number, and distribution depending on the genotype of HPV involved and the immune status of the patient. Human papillomaviruses comprise five genera (alpha, beta, gamma, mu, and nu papillomavirus) with different life-cycle characteristics, epithelial tropisms, and disease associations. Epidermodysplasia verruciformis (EV) is a rare, lifelong, autosomal recessive skin disease characterized by persistent cutaneous human papillomavirus infection not necessarily associated with immune system defects. The disease results from an unusual genetic susceptibility to infections with various types of HPVs (especially ß-HPV), some of which cause malignant transformation. Conversely, generalized verrucosis has been more typically associated with generalized warts, which are associated with immunocompromised conditions.

Pseudoxanthoma elasticum and skin: Clinical manifestations, histopathology, pathomechanism, perspectives of treatment.

Pseudoxantoma elasticum (PXE), also known as Groenblad-Strandberg syndrome, is a rare heritable disease with an estimated prevalence of 1:50,000 in the general population. PXE is considered a prototype of multisystem ectopic mineralization disorders and it is characterized by aberrant mineralization of soft connective tissue with degeneration of the elastic fibers, involving primarily the eyes, the cardiovascular system, and the skin. Cutaneous lesions consist of small, asymptomatic, yellowish papules or larger coalescent plaques, typically located on the neck and the flexural areas. PXE is caused by mutations in the ABCC6 (ATP-binding cassette subfamily C member 6) gene that encodes a transmembrane ATP binding efflux transporter, normally expressed in the liver and the kidney; however, the exact mechanism of ectopic mineralization remains largely unknown. The histological examination of cutaneous lesions, revealing accumulation of pleomorphic elastic structures in middermis, is essential for the definitive diagnosis of PXE, excluding PXE-like conditions. PXE is currently an intractable disease; although the cutaneous findings primarily present a cosmetic problem, they signify the risk for development of ocular and cardiovascular complications associated with considerable morbidity and mortality. The purpose of this review is to present a comprehensive overview of this rare form of hereditary connective tissue disorders, focus on the pathogenesis, the clinical manifestation, and the differential diagnosis of PXE. Emphasis is also placed on the management of cutaneous lesions and treatment perspectives of PXE.

Elastosis perforans serpiginosa: a case successfully treated with intralesional steroids and topical allium cepa-allantoin-pentaglycan gel.

Elastosis perforans serpiginosa is a rare skin disease in which abnormal elastic fibers, other connective tissue elements, and cellular debris are expelled from the papillary dermis through the epidermis. Three clinical variants of EPS can be detected: idiopathic, reactive, and drug-induced. Clinically it consists of small horny or umbilicated papules arranged in a linear, arciform, circular, or serpiginous pattern. It usually occurs in young adults and shows a predilection for the head and neck. The lesions are generally asymptomatic or slightly itching. Several treatments have been reported with poor long-term success; these include intralesional and topical corticosteroids, tazarotene, imiquimod, and cryotherapy. We report a case of 40-year-old black woman affected by elastosis perforans serpiginosa that was referred to our department and treated with intralesional injections of triamcinolone acetonide and topical application of allium cepa-allantoin-pentaglycan gel.

Factitious disorders in adults: two cases of unusual skin ulcers.

The factitious disorders (FDs) include a large group of dermatological conditions characterized by skin lesions that patients themselves self-inflict but deny their active participation. FDs usually represent a diagnostic challenge, and their therapeutic management is usually based on a multidisciplinary approach because most FRD patients also suffer from undiagnosed behavior and personality disorders. We report two cases of FD: one patient that was suffering from severe depression and induced third-degree chemical burns on his own lower limbs, and another patient affected by obsessive-compulsive disorder and anorexia nervosa that presented with deep self-inflicted ulcers on her face. Our multispecialist approach, based on close cooperation between dermatologists and psychiatrists, led to a significant improvement of clinical conditions in both cases. Dermatologists need to be aware that FDs are complex disorders and a multidisciplinary approach is usually recommended to control their clinical course.

Long-term effects on cortical excitability and motor recovery induced by repeated muscle vibration in chronic stroke patients.

BACKGROUND: Muscle vibration modifies corticomotor excitability in healthy subjects and reduces muscle tonus in stroke patients. OBJECTIVE: This study examined whether repeated muscle vibration (rMV) applied over the flexor carpi radialis (FCR) and biceps brachii (BB) can induce long-lasting changes, using transcranial magnetic stimulation (TMS), in patients with chronic stroke. METHODS: Thirty hemiparetic patients who offered at least minimal wrist and elbow isometric voluntary contractions were randomly assigned to either an experimental group, which received rMV in addition to physiotherapy (rMV + PT), or a control group that underwent PT alone. The following parameters of the FCR, BB, and extensor digitorum communis (EDC) were measured through TMS before, and 1 hour, 1 week, and 2 weeks after the end of intervention: resting motor threshold (RMT), map area, map volume, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Muscle tonus and motor function were assessed on the same day as TMS. RESULTS: Pre-post analysis revealed a reduction in RMT and an increase in motor map areas occurred in the vibrated muscles only in the rMV + PT group, with an increase in map volumes of all muscles. Moreover, SICI increased in the flexors and decreased in the extensor. These neurophysiological changes lasted for at least 2 weeks after the end of rMV + PT and paralleled the reduction in spasticity and increase in motor function. A significant correlation was found between the degree of spasticity and the amount of intracortical inhibition. CONCLUSION: rMV with PT may be used as a nonpharmacological intervention in the neurorehabilitation of mild to moderate hemiparesis.

Effect of allium cepa-allantoin-pentaglycan gel on skin hypertrophic scars: clinical and video-capillaroscopic results of an open-label, controlled, nonrandomized clinical trial.

BACKGROUND: Hypertrophic scar formation is a process in which prolonged angiogenesis sustained by vascular endothelial growth factor cutaneous expression plays an important role. OBJECTIVE: This in vivo study was conducted to evaluate the clinical effect of a topical gel containing onion extract, allantoin, and pentaglycan on hypertrophic scars and keloids. MATERIALS AND METHODS: Thirty people with hypertrophic scars or keloids were examined. Fifteen patients received a topical application of a gel containing allium cepa, allantoin, and pentaglycan twice a day for 24 weeks, the remaining 15 patients received no topical treatments. A clinical evaluation and an intravital videocapillaroscopy were performed on every patient at baseline (T0) and 24 weeks (T24) after the treatment. RESULTS: Only the patients who received the topical treatment showed a significant reduction in neoangiogenetic features, demonstrated through an improvement of erythema and all videocapillaroscopic markers of neoangiogenesis. These changes induced by therapy led to a general improvement of the lesions. CONCLUSION: Topical applications of a gel containing allium cepa, pentaglycan, and allantoin twice a day for 24 weeks seems to be useful in reducing neoangiogenesis in hypertrophic scars and keloids, resulting in clinical improvement of skin lesions. The authors have indicated no significant interest with commercial supporters.

TMS activation of interhemispheric pathways between the posterior parietal cortex and the contralateral motor cortex.

Using a twin coil transcranial magnetic stimulation (tc-TMS) approach we have previously demonstrated that facilitation may be detected in the primary motor cortex (M1) following stimulation over the ipsilateral caudal intraparietal sulcus (cIPS). Here we tested the interhemispheric interactions between the IPS and the contralateral motor cortex (M1). We found that conditioning the right cIPS facilitated contralateral M1 when the conditioning stimulus had an intensity of 90% resting motor threshold (RMT) but not at 70% or 110% RMT. Facilitation was maximal when the interstimulus interval (ISI) between cIPS and M1 was 6 or 12 ms. These facilitatory effects were mediated by interactions with specific groups of interneurons in the contralateral M1. In fact, short intracortical inhibition (SICI) was reduced following cIPS stimulation. Moreover, additional comparison of facilitation of responses evoked by anterior-posterior versus posterior-anterior stimulation of M1 suggested that facilitation was more effective on early I1/I2 circuits than on I3 circuits. In contrast to these effects, stimulation of anterior IPS (aIPS) at 90% RMT induced inhibition, instead of facilitation, of contralateral M1 at ISIs of 10-12 ms. Finally, we found similar facilitation between left cIPS and right M1 although the conditioning stimuli had to have a higher intensity compared with stimulation of right cIPS (110% instead of 90% RMT). These findings demonstrate that different subregions of the posterior parietal cortex (PPC) in humans exert both facilitatory and inhibitory effects towards the contralateral primary motor cortex. These corticocortical projections could contribute to a variety of motor tasks such as bilateral manual coordination, movement planning in space and grasping.

Changes in intracortical circuits of the human motor cortex following theta burst stimulation of the lateral cerebellum.

OBJECTIVE: The cerebellum takes part in several motor functions through its influence on the motor cortex (M1). Here, we applied the theta burst stimulation (TBS) protocol, a novel form of repetitive Transcranial Magnetic Stimulation (rTMS) over the lateral cerebellum. The aim of this study was to test whether TBS of the lateral cerebellum could be able to modulate the excitability of the contralateral M1 in healthy subjects. METHODS: Motor-evoked potentials (MEPs) amplitude, short intracortical inhibition (SICI), long intracortical inhibition (LICI) and short intracortical facilitation (SICF) were tested in the M1 before and after cerebellar continuous TBS (cTBS) or intermittent TBS (iTBS). RESULTS: We found that cTBS induced a reduction of SICI and an increase of LICI. On the other hand, cerebellar iTBS reduced LICI. MEPs amplitude also differently vary following cerebellar stimulation with cTBS or iTBS, resulting in a decrease by the former and an increase by the latter. CONCLUSIONS: Although the interpretation of these data remains highly speculative, these findings reveal that the cerebellar cortex undergoes bidirectional plastic changes that modulate different intracortical circuits within the contralateral primary motor cortex. SIGNIFICANCE: Long-lasting modifications of these pathways could be useful to treat various pathological conditions characterized by an altered cortical excitability.

Hyperexcitability of parietal-motor functional connections in the intact left-hemisphere of patients with neglect.

Hemispatial neglect is common after unilateral brain damage, particularly to perisylvian structures in the right-hemisphere (RH). In this disabling syndrome, behaviour and awareness are biased away from the contralesional side of space towards the ipsilesional side. Theoretical accounts of this in terms of hemispheric rivalry have speculated that the intact left-hemisphere (LH) may become hyper-excitable after a RH lesion, due to release of inhibition from the damaged hemisphere. We tested this directly using a novel twin-coil transcranial magnetic stimulation (TMS) approach to measure excitability within the intact LH of neglect patients. This involved applying a conditioning TMS pulse over left posterior parietal cortex (PPC), in order to test its effect on the amplitude of motor evoked potentials (MEPs) produced by a subsequent test pulse over left motor cortex (M1). Twelve RH stroke patients with neglect, an age-matched group of eight RH stroke patients without neglect, and 10 healthy controls were examined. We found that excitability of left PPC-M1 circuits was higher in neglect patients than the other groups, and related to the degree of neglect on clinical cancellation tests. A follow-up found that 1 Hz repetitive TMS over left PPC normalized this over-excitability, and also ameliorated visual neglect on an experimental measure with chimeric objects. Our results provide 'direct' evidence for pathological over-excitability of the LH in the neglect syndrome, as quantified by left PPC influences on left M1, with implications for possible treatment.

Long-term effects on motor cortical excitability induced by repeated muscle vibration during contraction in healthy subjects.

OBJECTIVE: The effects of a novel repeated muscle vibration intervention (rMV; 100 Hz, 90 min over 3 consecutive days) on corticomotor excitability were studied in healthy subjects. METHODS: rMV was applied over the flexor carpi radialis (FCR) during voluntary contraction (experiment 1), during relaxation and during contraction without vibration (experiment 2). Focal transcranial magnetic stimulation (TMS) was applied before rMV and one hour, and one, two and three weeks after the last muscle vibration intervention. At each of these time points, we assessed the motor map area and volume in the FCR, extensor digitorum communis (EDC) and abductor digiti minimi (ADM). Short-interval intracortical inhibition (SICI) and facilitation (ICF) were tested for the flexor/extensor muscles alone. RESULTS: Following rMV under voluntary contraction, we observed a significant reduction in the FCR map volumes and an enhancement in the EDC. SICI was increased in the FCR and reduced in the EDC. These changes persisted for up to two weeks and occurred at the cortical level in the hemisphere contralateral to the side of the intervention. CONCLUSION: We conclude that rMV, applied during a voluntary contraction, may induce prolonged changes in the excitatory/inhibitory state of the primary motor cortex. These findings may represent an important advance in motor disorder rehabilitation.

Lichen striatus in adults and pimecrolimus: open, off-label clinical study.

BACKGROUND: Lichen striatus is a well-known, acquired, self-healing, linear inflammatory dermatosis. Lichen striatus occurring in adults tends to be more extensive and itchy than in children, sometimes requiring symptomatic treatment. The therapeutic approach usually adopted is topical steroids, even though prolonged use may lead to several side-effects, particularly cutaneous atrophy. OBJECTIVE: To report the results of an open, off-label study on the use of pimecrolimus 1% in the treatment of diffuse, nonresponsive forms of lichen striatus. METHODS: Three adult patients suffering from relapsing or disseminated and itchy lichen striatus received topical application of pimecrolimus 1% cream (Elidel, Novartis Pharma, Basle, Switzerland) twice daily for 6 weeks, or until complete disappearance of the cutaneous lesions. RESULTS: All patients experienced rapid healing of the dermatosis, without any recurrence for at least 14 months. CONCLUSION: Our preliminary results show that pimecrolimus may represent a useful therapeutic alternative for lichen striatus, although further studies on a larger number of cases are needed to confirm its safety and efficacy in the treatment of this condition.