J AM ACAD DERMATOL VOLUME 53, NUMBER 5 Brief reports 881 Symptomatic treatment of idiopathic and rosacea- associated cutaneous flushing with propranolol Helen Craige, MD, and Jack B. Cohen, DO Dallas, Texas Flushing has been associated with medications, rosacea, menopause, carcinoid syndrome, pheochromo- cytoma, polycythemia, and mastocytosis, although it can occur without known cause. There are no known specific treatments available, but b-blockers have suppressed flushing reactions in some patients, particularly when associated with anxiety. The medical histories and clinical characteristics of 9 patients with either idiopathic flushing or flushing associated with rosacea were reviewed. Eight patients experienced subjective improvement with propranolol therapy. ( J Am Acad Dermatol 2005;53:881-4.) F ingestion, and with rare conditions, such as carcinoid syndrome, pheochromocytoma, polycythemia, and mastocytosis.1,2Flushing also occurs in the absence of any known cause. Despite its benign nature, some patients find their symptoms disabling. The b- blockersnadolol3andpropranolol1,4havesuppressed flushing reactions in some patients, particularly when associated with anxiety. We present our findings of 9 patients with flushing treated with propranolol. and had symptom duration between 1 and 10 years. Facial erythema or blushing on examination was noted in 8 patients. Heat was the most common aggravating factor, but sunlight induced flushing in 4 patients. One patient reported that fluorescent lights made her flushing worse. Eight patients had eryth- ematotelangiectatic or papular rosacea and one had idiopathic flushing. Four patients with rosacea had associated symptoms that occurred with each epi- sode: 3 with a burning sensation, and one with stinging. Medical histories revealed one patient with hypertension, 4 with allergic rhinitis or sinus aller- gies, 3 with headaches (2 migraine), and 3 patients had fibromyalgia. Eight of the 9 patients reported diminished symp- toms and fewer flushing episodes while taking propranolol. None had sufficient relief from the initial dosage of propranolol, 10 mg taken 3 times a day. This dosage was then increased and individu- alized. The dose of propranolol needed to achieve symptomatic control of flushing varied between 20 and 40 mg taken twice daily to 3 times a day (Table II). For patient 2, long-acting propranolol, 80 mg daily, was substituted for a calcium channel blocker that controlled her hypertension without affecting her flushing. This propranolol formulation controlled her blood pressure and decreased her flushing symptoms. Patient 3, the only male patient in the study, did not have his flushing improve with propranolol. However, he only received 10 mg of propranolol 3 times a day for 1 month without side effects and then elected to discontinue propranolol altogether. Twopatientsexperiencedadversesideeffectsthat necessitated discontinuation of propranolol. Patient 1 had significant improvement of her flushing, but her pulse rate decreased and she experienced some dizziness. Patient 8 had mild improvement, but dizziness and a sensation of balance loss developed lushing, aperiodic exaggeration of the normal blush response, has been associated with rosacea, menopause, alcohol or nicotinic acid METHOD Medical records of patients with flushing treated with propranolol were reviewed retrospectively to compareage, sex, duration,distribution, aggravating factors, symptomatology, and co-occurring illnesses. All but one patient was treated initially with pro- pranolol, 10 mg, by mouth 3 times daily, with doses increased as tolerated until symptoms improved. Success was measured by each patient’s perception of improvement, based on decreasing flushing episodes, decreasing symptoms, and quality of life (Tables I and II). RESULTS All but one patient were female and all were Caucasian. They ranged in age from 31 to 69 years From the Department of Dermatology, University of Texas Southwestern Medical School. Funding sources: None. Conflicts of interest: None identified. Reprint requests: Jack B. Cohen, DO, Department of Dermatology, UT Southwestern Medical School, 5323 Harry Hines Blvd, Dallas, TX 75390-9190. E-mail: firstname.lastname@example.org. 0190-9622/$30.00 ª 2005 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2005.07.021
J AM ACAD DERMATOL NOVEMBER 2005 882 Brief reports Table I. Summary of case presentations Ethnic origin/ Sex Duration of symptoms (y) Distribution of flushing Presence of blush on exam Patient no. Age (y) Aggravating factors Other symptoms 1 42 Caucasian/F 3 Nose, cheeks, chin, ears, anterior neck Cold or hot weather, alcohol ingestion, stress Sun and heat exposure Yes None 2 53 Hispanic/F 10 Malar cheeks and nose Nose, cheeks, chin, lower forehead Diffuse background erythema on face Yes None 3 31 Caucasian/M 1 Heat, alcohol ingestion No None 4 35 Caucasian/F 2 Anger, heat, nervousness, sun, wind, or cold exposure Heat, stress, sun exposure Yes None 5 52 Caucasian/F 2 Forehead, medial cheeks, chin, nose Cheeks, chin, nose Face and anterior neck Face, neck, ears, chest, scalp; left side more than right Cheeks, chin Yes Burning sensation 6 7 31 69 Caucasian/F Caucasian/F 2 Mowing the lawn Heat, stress Yes Yes None Burning sensation Burning sensation 10 8 43 Caucasian/F 2 Heat, fluorescent lights, stress, and sun exposure Yes; preferred to sit in a dark room Yes 9 35 Caucasian/F 1 Exercise; sometimes flushing wakes her at night Stinging when her propranolol dose reached 40 mg 3 times a day. Patient 4 attributed her mild weight gain to propranolol, but she continued it because propran- olol was effective in treating her flushing and head- aches. The two patients with known histories of migraine headache also experienced the positive side effect of decreased severity of headaches while taking propranolol. for an underlying systemic cause. Once systemic diseases and medications are excluded, flushing is most commonly associated with rosacea and meno- pause, although it may also be idiopathic. Flushing that accompanies menopause is usually amenable to estrogen replacement therapy. On the other hand, flushing associated with rosacea commonly fails to respond to standard therapies for rosacea. Idiopathic flushing tends to occur in women and the symptoms persist for a long duration.2 Treatmentofflushingisdifficultprimarilybecause it has been associated with multiple etiologies. Improvement in transient flushing is also difficult to quantitate, although attempts to provoke flushing and to measure the responses to medications have been performed. Even so, only small series and case reports are found in the literature. Friedman et al2 described 10 patients with idiopathic flushing. These patients failed to respond to one or more therapies including H1 and H2 antihistamines, aspirin and nonsteroidal anti-inflammatory steroids, calcium channel blockers, danazol, and cromolyn sodium. In another report, clonidine re- duced malar temperature in patients with erythema- totelangiectatic rosacea, despite the failure to reduce redness after provocative maneuvers.5Although DISCUSSION Flushing of the face, chest, and neck occurs most commonly in individuals with fair complexion, par- ticularly those of Celtic or northern European ances- try. The redness is often transient, but it may become persistent, and telangiectasia can occur. Patients are not only distressed by the visual redness; many also complain of symptoms such as burning, stinging, and heat associated with each episode. These symp- toms even caused several patients to carry handheld or battery-operated fans and spray bottles with cold water for relief. Patient 5, whose symptoms were aggravated by light, preferred to remain in a dark- ened room. Flushing that is accompanied by other symptoms, including abdominal pain, dyspnea, palpitations, and frequent stools, should prompt further work-up drugs, systemic
J AM ACAD DERMATOL VOLUME 53, NUMBER 5 Brief reports 883 Table II. Diagnoses, treatment, and side effects Patient no. Other medical diagnoses b Blocker dose* Systemic medications Side effects 1 Rosacea, fibromyalgia None Propranolol, 10 mg, 20 mg q afternoon and 10 g qhs Propranolol LA 80 mg qd Decreased heart rate, fatigue, dizziness 2 Rosacea, contact dermatitis, migraines, depression, sinus allergies, hypertension Estrogen Sertraline Rabeprazole Fexofenadine Tetracycline Valsartan Controlled migraine headaches 3 Psoriasis, rosacea, hypertension, peptic ulcer disease Propranolol 10 mg tid for 1 mo gave no relief of symptoms; patient discontinued drug Propranolol 20 mg tid None 4 Allergic rhinitis, seborrheic dermatitis, headaches Fexofenidine Aspirin 81 mg Cetirizine Aspirin 81 mg Cetirizine Tetracycline Oral contraceptive pills Aspirin 81 mg Morphine Alprazolam Lorazepam Cyclobenzaprine Lansoprazole Gabapentin Amitriptyline Oral contraceptive pills Levothyroxine Weight gain, less headaches 5 6 Rosacea, atopic dermatitis Fibromyalgia, atopic dermatitis, rosacea, migraine headaches Propranolol 40 mg tid Propranolol 40 mg bid None Less migraine headaches 7 8 Rosacea Fibromyalgia, chronic pain syndrome, allergic rhinitis, rosacea Propranolol 20 mg bid Propranolol 40 mg tid None Transient dizziness and sense of balance loss 9 Hypothyroidism, rhinitis, rosacea Propranolol 20 mg tid None bid, Twice daily; q, every; qd, daily; qhs, at bed time; LA, long-acting; tid, 3 times a day. *The dose required for subjective relief of symptoms. b-blockershavealsonotdemonstratedobjectivelab- oratory evidence for direct effects on cutaneous blood vessels during flushing episodes, some pa- tients have reported fewer symptoms.1,3,4Single case reports exist for improvement of resistant flushing with thoracoscopic sympathectomy6and injection of botulinumtoxinA.7,8Biofeedbacktrainingalsofailed to show objectively measured decreases in flushing.9 Cutaneous flushing is frequently associated with anxiety reactions.10 Nonselective b-blockers are knowntodecreasesympatheticactivity andtoreduce the symptoms of anxiety in normal subjects.3,11,12 According to Abelson, Nesse, and Vinik,10there is a significant overlap between patients with panic disor- der and idiopathic flushing. In addition, b-blockers may reduce episodes of tachycardia that are known to intensify flushing symptoms.3 Beta-blocker therapy should be monitored for side effects. Fatigue, somnolence, and dizziness are reported by approximately 10% of patients. Dyspnea, vivid dreams, confusion, and bradycardia can occur in up to 3% of patients, although only 1% experience hypotension. Sexual dysfunction can occur in male patients, especially with the nonselec- tive b-blockers propranolol and pindolol.13Caution should be exercised in prescribing b-blockers to patients with asthma14and psoriasis,15whose dis- eases may worsen. Symptomatic idiopathic flushing and flushing as- sociated with rosacea deserve separate treatment, since the flushing does not respond to conventional rosacea treatment. Although the perceived improve- ment of flushing and its symptoms in 8 of our 9 patients treated with propranolol is encouraging, prospectiverandomizedstudieswithcontrolsubjects and standardized quality of life data are necessary to better determine the efficacy of propranolol therapy. REFERENCES 1. Tur E, Ryatt KS, Maibach HI. Idiopathic recalcitrant facial flushing syndrome. Dermatologica 1990;181:5-7.
J AM ACAD DERMATOL NOVEMBER 2005 884 Brief reports 2. Friedman BS, Germano P, Miletti J, Metcalfe DD. A clinico- pathologic study of ten patients with recurrent unexplained flushing. J Allergy Clin Immnunol 1994;93:53-60. 3. Wilkin JK. Effect of nadolol on flushing reactions in rosacea. J Am Acad Dermatol 1989;20:202-5. 4. Drummond PD. The effect of adrenergic blockade on blushing and facial flushing. Psychophysiology 1997;34:163-8. 5. Wilkin JK. Effect of subdepressor clonidine on flushing of reactions in rosacea. Arch Dermatol 1983;119:211-4. 6. Krasna MJ, Jiao X, Sonett J, Gamliel Z, King K. Thoracoscopic sympathectomy. Surg Laprosc Endosc Percutan Tech 2000;10: 314-8. 7. Yuraitis M, Jacob CI. Botulinum toxin for the treatment of facial flushing. Dermatol Surg 2004;30:102-4. 8. Sterodimas A, Nicolaou M, Paes TRF. Successful use of botu- linum toxin-A for the treatment of neck and anterior chest wall flushing. Clin Exp Dermatol 2003;28:592-4. 9. Wilkin JK, Tarbox A. Biofeedback training in the therapy of flushing. Cutis 1983;31:74-5. 10. Abelson JL, Nesse RM, Vinik A. Treatment of panic-like attacks with long-acting analogue of somatostatin. J Clin Psychophar- macol 1990;10:128-32. 11. Rosenbaum JF. The drug treatment of anxiety. N Engl J Med 1982;306:401-4. 12. Peat M. Beta blockade in anxiety. Postgrad Med J 1984; 60(Suppl 2):16-8. 13. Rosen RC, Kostis JB, Jekelis AW. Beta-blocker effects on sexual function in normal males. Arch Sex Behav 1988;17:241-55. 14. Patakas D, Agriropoulou V, Louridas G, Tsara V. Beta-blockade in bronchial asthma; effect of propranolol and pindolol on large and small airways. Thorax 1983;38:108-12. 15. Abel EA, DiCicco LM, Orenberg EK, Fraki JE, Farber EM. Drugs in exacerbation of psoriasis. J Am Acad Dermatol 1986;15: 1007-22. Dermoscopy of the nail bed and matrix to assess melanonychia striata Sergio H. Hirata, MSc,aSergio Yamada, MSc,aFernando A. Almeida, PhD,a Jane Tomomori-Yamashita, PhD,aMauro Y. Enokihara, PhD,aFrancisco M. Paschoal, PhD,c Milvia M. Enokihara, PhD,bCinthia M. Outi, MD,aand Nilceo S. Michalany, MScb Sa ˜o Paulo, Brazil Melanonychia striata represents a diagnostic dilemma for dermatologists. The use of dermoscopy to assess the nail has advantages over clinical examination. However, when compared to skin lesions, it gives fewer details. We describe two cases of melanonychia striata submitted to dermoscopic examination of the nail bed and matrix. This is a new procedure that enables observing dermoscopic characteristics that are not visualized in the nail plate, thus, providing additional information. ( J Am Acad Dermatol 2005;53:884-6.) M oftenimpossibletoidentifythecauseoftheselesions using clinical examination alone. There are advantages to the adjuvant use of dermoscopy in assessing nail abnormalities.2-4How- ever, as opposed to the dermoscopic assessment of skin lesions in which melanin distribution and struc- ture are examined directly at the site of origin, fewer details can be seen dermoscopically in the nail.5Ex- aminationofnaillesionsislimitedtothepigmentthat isdepositedinthenailplateasaresultofmelanocytic activity that occurred in the nail matrix, bed, or both. Therefore, dermoscopic characteristics observed in thenail plate can misrepresent theunderlying lesion. Two cases of melanonychia striata (melanoma and hypermelanosis/racial melanonychia) are de- scribed to exemplify the difficulty faced when mak- ing a diagnosis. Both patients were submitted to dermoscopic examination of the nail plate, bed, and matrix. Dermoscopic examination of the nail bed and matrix enables visualizing pigmentation directly in its original site, revealing aspects not observed when the nail plate is interposed between the pig- mented lesion and the Dermatoscope (Dermlite, 3 Gen, LCC, Dana Point, Calif). elanonychia striata can be neoplastic or benign in nature.1This represents a diag- nostic dilemma for dermatologists, as it is From the Departments of Dermatologyaand Pathology,bFederal University of Sa ˜o Paulo, and Department of Dermatology, Faculdade de Medicina do ABC.c Funding sources: None. Conflicts of interest: None identified. Reprint requests: Sergio H. Hirata, Rua Taquarussu 245, Sa ˜o PauloeSP Cep: 04346-040, Brazil. E-mail: email@example.com. 0190-9622/$30.00 ª 2005 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2005.07.032