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Angular Cheilitis, Part 2: Nutritional, Systemic, and Drug-Related Causes and Treatment

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Angular Cheilitis, Part 2: Nutritional, Systemic, and Drug-Related Causes and Treatment Angular Cheilitis, Part 2: Nutritional, Systemic, and Drug-Related Causes and Treatment Kelly K. Park, MD; Robert T. Brodell, MD; Stephen E. Helms, MD Angular cheilitis (AC) is associated with a variety Anemia has been associated with AC in as much of nutritional, systemic, and drug-related factors as 11.3% to 31.8% of patients in several studies.5-8 that may act exclusively or in combination with Although this incidence rate may not be applicable local factors. Establishing the underlying etiology in the United States today, there is still a consider- of AC is required to appropriately focus treat- able number of patients with nutritional deficiencies ment efforts. resulting in AC in third world countries.5,6,9 Cutis. 2011;88:27-32. Chronic iron deficiency can cause koilonychia, glossitis, and cheilosis with fissuring. The mechanism for AC in these patients has not been fully eluci- ngular cheilitis (AC) was described in depth dated, but it has been suggested that iron deficiency in part 1 of this articleCUTIS with a focus on local decreases cell-mediated immunity, thereby promoting A etiologic factors.1 Part 2 reviews the causes of mucocutaneous candidiasis.10 AC that may not be so readily apparent including Riboflavin (vitamin B2) deficiency often is accom- nutritional, systemic, and drug-related factors. When panied by a mixed vitamin B complex deficiency due treatment focused on local etiologies (irritant, aller- to its role in the metabolism of vitamin B6 and trypto- gic, and infectious) has been exhausted, less common phan, the latter of which is then converted to niacin causes should be identified to effectively treat what (vitamin B3). Generally, riboflavin deficiency will can Dobecome a chronic condition. Notpresent Copyas redness of the mucous membranes, AC, and magenta-colored glossitis.11 It may also present Nutritional Deficiencies as oculo-oro-genital syndrome, characterized by the Angular cheilitis can herald a variety of nutritional following changes: perlèche or cheilosis, magenta- deficiencies that can have potentially debilitating colored glossitis, interstitial keratitis and corneal effects (Table 1). Identification of these deficien- vascularization, and scrotal and vulvar lesions.3 cies followed by nutrient replenishment is critical Pyridoxine (vitamin B6) deficiency causes chei- for these patients. Deficiencies of iron and various losis; glossitis; and seborrhealike changes around the B vitamins account for as many as 25% of cases of AC.4 mouth, eyes, and nose. It often occurs in alcoholics and may occur in patients on medications that impair vitamin B6 metabolism, which includes cycloserine, isoniazid, hydralazine hydrochloride, oral contracep- All from the Dermatology Section, Northeastern Ohio Universities tives, D-penicillamine, and levodopa (when taken College of Medicine, Rootstown. Dr. Park also is from the University without carbidopa).12 of California, San Francisco. Dr. Brodell also is from Case Western Reserve University School of Medicine, Cleveland, Ohio, and Decreased vitamin B12 (cyanocobalamin) levels University of Rochester School of Medicine and Dentistry, New York. make patients vulnerable to the development of AC. Dr. Helms also is from Case Western Reserve University School It commonly is associated with malnutrition, alcohol- of Medicine. ism, and pernicious anemia. Other causes include ter- The authors report no conflict of interest. minal ileum resection or disease (common in Crohn Correspondence: Kelly K. Park, MD, The Psoriasis & Skin Treatment Center, Phototherapy & Clinical Research Unit, Department of disease), postgastrectomy states, chronic pancreatitis, Dermatology, University of California, San Francisco, 515 Spruce St, strict vegan diets, and infection with Diphyllobothrium San Francisco, CA ([email protected]). latum. Vitamin B12 levels are changed by WWW.CUTIS.COM VOLUME 88, JULY 2011 27 Copyright Cutis 2011. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Angular Cheilitis Table 1. Nutritional Deficiencies Implicated in Angular Cheilitis Etiology Diagnostic Test Treatment Iron2 Serum iron, total iron-binding 50–65 mg elemental iron orally 3–4 times capacity, serum ferritin daily (,300 mg daily) 3 Riboflavin (vitamin B2) Elevated RBC glutathione 5–15 mg daily reductase level 3 Pyridoxine (vitamin B6) Pyridoxal 5ʹ-phosphate level 50 mg daily or 100–200 mg daily (this dosing if deficiency is drug related) Cyanocobalamin CBC (megaloblastic anemia), 500 μg in 1 nostril once weekly, then main- 3 (vitamin B12) serum cobalamin level, elevated tenance therapy 25 μg in each nostril daily; serum methylmalonic acid level or 250 μg orally daily; or 30 μg per day intra- muscularly for 5–10 days, then maintenance therapy 100–200 μg intramuscularly monthly Folic acid3 CBC (megaloblastic anemia), Folic acid 5–15 mg orally daily serum folate Niacin3 2-pyridone and 2-methyl Nicotinamide (preferred) or nicotinic acid nicotinamide urinary excretion 100–200 mg 3 CUTIS Zinc Serum zinc ,70 μg/dL 60 mg elemental zinc orally twice daily Abbreviations:Do RBC, red blood cell; CBC,Not complete blood cell count. Copy cholestyramine, colestipol, p-aminosalicylic acid, and dementia), can result in glossitis or cheilitis and has potassium chloride.12 been found to be a more frequent cause of AC than A single case study of patients with glossitis and/or riboflavin deficiency.14 cheilosis refractory to other vitamin B nutrients dem- The final vitamin B deficiency associated with onstrated the effectiveness of treatment with calcium AC is biotin (vitamin BW or vitamin H). Patients pantothenate, a source of vitamin B5 (pantothenic may present with AC along with other symptoms acid or pantothenate).13 such as dry eyes and alopecia.15 Folate deficiency often presents with vitamin B12 In addition to vitamin deficiencies, mineral defi- deficiency and is characterized by stomatitis, glossitis, ciency can cause AC. Lack of the essential mineral and megaloblastic anemia. Folate supplementation is zinc is characterized by the triad of diarrhea; alopecia; affected by methotrexate, phenytoin, phenobarbital, and dermatitis manifesting as eczematous and erosive primidone, oral contraceptives, and triamterene.12 changes around the mouth as well as the acral and Chronic alcoholism, tropical and celiac sprues, genital areas. Angular cheilitis, glossitis, and pustular pancreatic diseases, malnutrition, and other mal- paronychia also are seen. In fact, AC is a common absorption syndromes can produce multinutrient early sign of acrodermatitis enteropathica and heralds 3 deficiencies leading to folate, vitamin B12, and iron relapse in these patients. Angular cheilitis can be deficiencies, which can lead to AC. caused by an autosomal recessive hereditary defi- Pellagra, the deficiency of niacin (vitamin B3) and ciency known as acrodermatitis enteropathica. It may protein, causing the 3 d’s (dermatitis, diarrhea, and be seen in association with cystic fibrosis, breastfed 28 CUTIS® WWW.CUTIS.COM Copyright Cutis 2011. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Angular Cheilitis preterm infants, high-cereal diets, and in 3% of alco- Glucagonomas are rare pancreatic neuroendocrine hol abusers (n5693).3,16 tumors that are correlated with necrolytic migra- tory erythema, weight loss, diabetes mellitus, ane- Systemic Disease mia, cheilitis, venous thrombosis, and neuropsychiatric A number of systemic diseases are associated with AC symptoms. Angular cheilitis has been described in asso- (Table 2). Angular cheilitis is very common in Down ciation with other mucous membrane involvement.31 syndrome, with a reported incidence of 25% (n577) Angular cheilitis often is the presenting sign in in one study. Associated factors may include lip lick- Plummer-Vinson syndrome, which is seen mostly in ing, picking, and Candida albicans infection.23 white middle-aged females and is characterized by the Xerostomia accounts for as much as 5% of AC triad of postcricoid dysphagia, upper esophageal webs, cases.4 Conditions that predispose patients to xero- and iron deficiency anemia.32 The etiology of AC in stomia include dehydration; salivary gland infec- Plummer-Vinson syndrome is iron deficiency anemia. tion, obstruction, and neoplasms; radiation to the Uremic stomatitis initially may present as AC mouth; chemotherapy; diabetes mellitus; neuropa- prior to mucosal dissemination. In uremia, ammo- thies; Sjögren syndrome; and nutritional deficiencies, nia by-products from increased salivary uremia and and it is a side effect of more than 300 medications.12 the action of bacterial urease become irritants at It also is associated with normal aging due to salivary the commissures.33 gland and duct atrophy and obstruction, predispos- Systemic infectious diseases also are implicated ing elderly patients to a decreased sense of taste, a in AC. In human immunodeficiency virus (HIV) burning sensation of the mouth, an increase in dental patients, the prevalence of AC is 5.6% to 28.9% caries, and AC.24,25 Without adequate saliva, it is dif- and it is the most common oral symptom of HIV in ficult to maintain oral hygiene, exacerbating the local children.34-36 This relationship is thought to be due infections associated with AC. to oropharyngeal candidiasis, which is estimated to Angular cheilitis also is seen in various forms of affect more than 90% of HIV patients at some point malnutrition and
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