tial effect, 3.0 (2.8) days (range, 1-7 days) for BT-B vs cal, and material support: Brigo, Acler, and Vicentini. Study 14.3 (6.7) days (range, 7-20 days) for BT-A. Anhidrotic supervision: Frasson and Bertolasi. areas developed earlier in the BT-B side. Patients re- Financial Disclosure: None reported. ported longer-lasting subjective benefit from BT-B than 1. Guttmann L. The management of the quinizarin sweat test (Q.S.T.). Postgrad BT-A: 17.3 (7.4) weeks vs 12.9 (8.4) weeks. Med J. 1927;23(262):353-366. All patients tolerated intradermally injected BT-A and 2. Naumann M, Lowe NJ. Botulinum toxin type A in treatment of bilateral pri- BT-B well, although some experienced mild pain, espe- mary axillary hyperhidrosis: randomised, parallel group, double blind, pla- cebo controlled trial. BMJ. 2001;323(7313):596-599. cially during BT-B injections. No hematomas developed 3. Dressler D, Adib Saberi F, Benecke R. Botulinum toxin type B for treatment at the injection site, nor did any participant report sys- of axillar hyperhidrosis. J Neurol. 2002;249(12):1729-1732. temic adverse effects. 4. Birklein F, Eisenbarth G, Erbguth F, Winterholler M. Botulinum toxin type B blocks sudomotor function effectively: a 6 month follow up. J Invest Dermatol. 2003;121(6):1312-1316. Comment. In all patients, although both toxins im- 5. Schlereth T, Mouka I, Eisenbarth G, Winterholler M, Birklein F. Botulinum proved axillary hyperhidrosis, BT-B proved more effec- toxin A (Botox) and sweating-dose efficacy and comparison to other BoNT tive than BT-A in reducing sweat production and area. preparations. Auton Neurosci. 2005;117(2):120-126. We therefore provide objective evidence that BT-B is safe and effective for treating bilateral axillary hyperhidro- sis.3,4 When administered at the same dose ratio of 1:50 used for the motor system, BT-B blocks sweating better Neurogenic Rosacea: A Distinct than BT-A. The subjective outcome measures, includ- Clinical Subtype Requiring ing the beginning and duration of benefit and treatment a Modified Approach to Treatment satisfaction scores, were also higher for BT-B than for BT-A treatment. osacea is generally categorized into 4 distinct Our finding that BT-B effectively reduces axillary hy- clinical subtypes: erythematotelangiectatic, perhidrosis differs from other studies probably because R papulopustular, phymatous, and ocular.1 the other studies used lower toxin ratios (1:40 or 1:20) Granulomatous rosacea, rosacea fulminans, and perioral and higher dilutions.3,4 Botulinum toxin type B might dermatitis have been described as additional variants.2 strongly reduce hyperhidrosis because it specifically tar- Herein we describe 14 patients with rosacea and promi- gets the autonomic nervous system, as happens in botu- nent neurologic symptoms, who represent another dis- lism type B.5 tinct subset of rosacea meriting a unique approach to Botulinum toxin type B merits increasing use in pal- management. mar hyperhidrosis to guarantee long-lasting benefit with- out hand muscle weakening. Future research should com- Methods. Patients with prominent neurologic symp- pare how BT-A and BT-B affect the autonomic and motor toms in addition to classic features of rosacea were iden- nervous systems and how long their action on both sys- tified during routine appointments at a major teaching tems lasts. hospital. Details regarding medical history, disease symp- toms and triggers, and response to treatments were ob- Emma Frasson, MD tained via clinic visits and telephone interviews. The study Francesco Brigo, MD was approved by the institutional review board of the Uni- Michele Acler, MD versity of California, San Francisco. Giuseppe Didonè, MD Silvana Vicentini, MS Results. Twelve of the 14 patients were women, and 12 Laura Bertolasi, MD were white. Mean age at disease onset was 38 years. Promi- nent symptoms included burning or stinging pain (100% Accepted for Publication: July 21, 2010. [14 of 14]), erythema (100% [14 of 14]), and flushing Author Affiliations: Department of Neurology, Cit- (93% [13 of 14]), sometimes accompanied by facial edema tadella Hospital, Padua, Italy (Drs Frasson and Didonè); (50% [7 of 14]), telangiectasias (50% [7 of 14]), pruri- and Department of Neurological Sciences and Vision, Sec- tus (43% [6 of 14]), and papules (36% [5 of 14]). Im- tion of Clinical Neurology, University of Verona, Ve- portant symptom triggers included heat (93% [13 of 14]), rona, Italy (Drs Brigo, Acler, Vicentini, and Bertolasi). sunlight (93%[13 of 14]), hot showers (79% [11 of 14]), Correspondence: Dr Frasson, Department of Neurol- stress (71% [10 of 14]), exercise (64% [9 of 14]), and ogy, Cittadella Hospital, Via Casa di Ricovero 40, Padua alcohol consumption (57% [8 of 14]). Use of makeup 35013, Italy ([email protected]). (50% [7 of 14]), eating spicy foods (43% [6 of 14]), touch- Author Contributions: All authors had full access to all ing skin (36% [5 of 14]), drinking hot beverages (29% the data in the study and take responsibility for the in- [4 of 14]), cold weather (21% [3 of 13]), and humidity tegrity of the data and the accuracy of the data analysis. (14% [2 of 13]) were less reliable triggers. Notably, 71% Study concept and design: Frasson and Bertolasi. Acquisi- of patients experienced relief from cooling via fans or cold tion of data: Frasson, Brigo, Acler, and Vicentini. Analy- compresses or ice applied to the face or held in the mouth sis and interpretation of data: Frasson, Brigo, Acler, and (10 of 14). Figure 1 depicts typical examination find- Didonè. Drafting of the manuscript: Frasson, Brigo, Acler, ings in these patients. and Vicentini. Critical revision of the manuscript for im- A notably high percentage of patients had neurologic portant intellectual content: Frasson, Didonè, and Berto- (43% [6 of 14]) or neuropsychiatric (50% [7 of 14]) con- lasi. Statistical analysis: Didonè. Administrative, techni- ditions, including complex regional pain syndrome, es- (REPRINTED) ARCH DERMATOL/ VOL 147 (NO. 1), JAN 2011 WWW.ARCHDERMATOL.COM 123 ©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 innate immunity.3 We believe neuronal dysregulation is equally integral to rosacea pathogenesis. It may contrib- ute to disease via various mechanisms, such as vaso- motor instability, release of proinflammatory neuro- peptides, and neuronal injury leading to perceived dysesthesias.4,5 In an individual patient, the relative im- portance of each of the mechanisms may differ, influ- encing both the spectrum of clinical symptoms and the optimal treatment strategy. We propose the diagnostic and treatment algorithm illustrated in Figure 2 as a guide for clinicians in man- aging a patient with suspected neurogenic rosacea. Pa- tients with prominent vasomotor symptoms, defined clini- cally by flushing and telangiectasias, may respond to vasoactive medications, including ␤-blockers, alpha-1 ad- renergic blockers, and calcium channel blockers. In ad- dition, laser- and light-based therapies seem to be more effective in this subset of patients. Patients with inflammatory features such as papules, pustules, or edema may respond, if symptoms are mild, to traditional topical therapies such as metronidazole, azelaic acid, or sulfur. Systemic antibiotics and antima- larial agents used for their anti-inflammatory effect may be useful for nonresponders. Figure 1. Facial erythema is seen in most patients at baseline and uniformly Finally, patients with dysesthesia out of proportion during flares. Inflammatory papules and pustules and rhinophymatous to flushing or inflammation can be difficult to treat and change are unusual in this subset of patients. require a unique approach first used to treat disorders such as complex regional pain syndrome and neuro- sential tremor, depression, and obsessive-compulsive dis- pathic itch. In our experience, neuroleptic agents (eg, gab- order. Neurovascular disorders, including headaches (71% apentin, pregabalin), tricyclic antidepressants, and pain- [10 of 14]) and Raynaud phenomenon (29% [4 of 14]), modifying antidepressants (eg, duloxetine) are the most as well as rheumatologic disorders (36% [5 of 14]), in- effective. N-methyl-D-aspartic acid receptor antagonists cluding lupus, rheumatoid arthritis, fibromyalgia, mixed (eg, memantine), systemic antibiotics, and other topi- connective tissue disease, and psoriatic arthritis, were also cally formulated medications (eg, ketamine, glycopyr- common. rolate, capsaicin) may be helpful in certain cases. Be- Many patients had tried the following treatments with cause of the associated heightened sensitivity to heat and limited success: topical metronidazole (0 of 12 were sunlight, laser- and light-based interventions should be helped), topical steroids (1 of 8), and oral antibiotics, usu- used with caution. ally tetracyclines (4 of 8). Most patients benefitted from Because our understanding of this enigmatic sub- neurologically focused treatments (9 of 12), including class of rosacea is extremely limited, further research is gabapentin (5 of 11), duloxetine (4 of 6), pregabalin (1 clearly needed to better describe the underlying patho- of 4), tricyclic antidepressants (2 of 3), and memantine physiologic characteristics and to identify additional ef- (2 of 2). Topically formulated neuroleptic agents, in- fective treatment methods. cluding doxepin, glycopyrrolate, amitriptyline, capsa- icin, and ketamine, were occasionally effective (3 of 7). Tiffany C. Scharschmidt, MD Hydroxychloroquine (3