The diagnostic importance of photosensitivity dermatoses in chronic alcoholism: Report of two cases
1. Department of Internal Medicine
Many of the vitamin deficiency diseases have been almost completely eliminated in developed countries. Niacin deficiency is considered one of them. However, cases of pellagra are recently reported in West Europe, USA, Australia, and Japan in connection with chronic alcoholism, gastrointestinal malabsorption, and some medications. We report two cases of pellagra, manifesting as photosensitivity dermatoses with mental deterioration in chronic alcoholic abusers in the Mediterranean basin, the island of Crete in Greece. The report highlights the fact that all physicians should be alerted to photosensitivity dermatoses in alcoholics; early treatment with multiple vitamin therapy, including nicotinic acid should be initiated in these patients.
Pellagra is a systemic disease caused by a cellular deficiency of niacin. It is frequent in Asia and Africa where the diet is corn-based and nicotinic acid deficient. Although it is considered that pellagra has been practically eradicated in developed countries, there are recent reports of pellagra from West Europe, USA, Australia, and Japan related to chronic alcoholism, gastrointestinal malabsorption, and some medications [1, 2, 3]. In Mediterrranean countries, where the periods of sunlight are long, cases of the disease are sporadically seen . We report two cases of pellagra, manifesting as photosensitivity dermatoses associated with mental deterioration in chronically alcoholic men on the island of Crete.
Case report 1
A 60-year-old chronic smoker and alcoholic man suffering from odynophagia, insomnia, epigastric discomfort and reccurent diarrhea presented to the outpatient department. Clinical examination revealed memory disorientation, stomatitis, glossitis, esophagitis, and exfoliative dermatitis with some vesicles on erythematous bases on photoexposed sites (Fig. 1). Blood examinations showed leukocytosis and serological markers (elevated AST, ALT, and γGT) of heavy drinking. Chest x-ray and abdominal ultrasound showed emphysematous lungs and fatty liver; CT of the brain was normal. Treatment with nicotinamide 500 mg daily was initiated after the presumptive diagnosis of pellagra. The rash improved and upon re-examination after three weeks the dermatitis had resolved. Moreover, it was suggested that he restrict alcohol and smoking and increase consumption of other B-complex vitamins and food sources of niacin.
Case report 2
A 57-year-old man was admitted to our department for management of chronic renal insufficiency, alcoholic cirrhosis and coronary ischemia. He was a heavy smoker and a chronic alcohol abuser. His medical history was significant for depression, dementia, and diabetes mellitus. Clinical examination showed a malnourished, socially isolated, anxious patient with bilaterally symmetrical erythema at the sites of solar exposure. The erythema on the dorsa of the hands and the feet had progressively evolved to vesicles and bullae, intensively pruritic, that were resolving with hyperpigmentation (Fig. 2). Initially the rash was considered a sunburn. Initially during hospitalization he was treated with B-complex vitamin tablets that did not contain niacin and the nervousness and irritability were increased. The patient's plasma level of ammonia was normal and the diagnosis of pellagra was made. The patient started on intravenous niacin (300 mg/daily) in combination with other B-complex vitamins. Dermatologic and neurologic manifestations improved significantly.
Pellagra is the most frequent clinical feature of nutritional deficiency in adults in rural populations in the Third World, whose staple diet is niacin deficient jawar or maize with inadequate animal protein, fruits and vegetables [5, 6]. In Europe and North America, cases of pellagra are rarely encountered and are related most commonly with chronic alcoholism [7, 8] and less frequently with gastro-intestinal malabsorption, carcinoid syndrome, liver cirrhosis, HIV infections , Hartnup disease, anorexia nervosa [10, 11], mycotoxins, excessive dietary leucine intake, and some medications (estrogens , 5-fluorouracil, isoniazid, pyrazinamide, 6-mercaptopurine, hydantoins, and phenobarbital [5, 6]).
The early symptoms of pellagra include loss of appetite, generalized weakness, irritability, abdominal pain and vomiting. Later symptoms are bright red glossitis, chronic or recurrent diarrhea (watery, but occasionally bloody), which leads to a state of malnutrition and cachexia. The characteristic skin rash is characterized by pigmentation and scaling, particularly involving the sun exposed areas . In acute pellagra the rash resembles sunburn (with symmetric erythema, vesicles and bullae accompanied by pruritus and burning). In advanced cases, the classic eruption forms a ring around the neck, known as "Casal's necklace." Exacerbations follow re-exposure to sunlight . As pellagra advances, neuropsychiatric symptoms such as photophobia, asthenia, depression, hallucinations, memory loss, and psychosis begin. The patient become disoriented, confused, and delirious; stupor and death result if untreated.
Nicotinic acid and nicotinamide are the two common forms of niacin. The amino acid, tryptophan, is its precursor and nicotinic acid dinucleotide (NAD) and nicotinic acid dinucleotide phosphate (NADP) are its active forms. The latter are crucial for the metabolism of carbohydrates, fatty acids, and proteins in highly metabolic tissues (liver, muscles, epidermis, and neural structures) [5, 14]. The pathogenesis of pellagra includes: (a) a deficiency of niacin (malnutrition) , (b) a congenital defect of intestinal and kidney absorption of tryptophan (Hartnup disease), (c) an increased conversion of tryptophan to serotonin (carcinoid syndrome), (d) a depletion of pyridoxal phosphate, that enhances the production of tryptophan (isoniazid), and (e) a decreased dermal content of collagen and urocanic acid, serving as filter for ultraviolet radiation (photosensitivity) .
Particularly in alcohol abusers, as described in the reported cases, the pathogenesis of pellagra has not been fully elucidated. It has not been determined if alcohol interferes directly with the absorption or synthesis of niacin as has been shown with thiamine. However, in developed countries, Alcoholic Pellagra Encephalopathy (APE), which exhibits a disturbance of consciousness, has been reported . Decreased intake, malabsorption, reduced storage, and impaired utilization of niacin  in a context of the increased metabolic needs in alcoholics are some of the main causes of pellagra in alcoholics. Finally, the high sun exposure in Mediterranean countries is an additional cause for the appearance of pellagra .
The diagnosis of pellagra is clinical, including the four "Ds": dermatitis, dementia, diarrhea, and death [10, 15]. However, it can be established by measurement of a decreased serum level of niacin, a low urinary level of N-methylnicotinamide and pyridone [6, 8, 10], and the improvement of cutaneous eruptions within 24-48 hours after oral niacin administration . Generally, the presence of characteristic skin lesions facilitates the diagnosis; the absence of them decreases the index of suspicion. Pellagra should be considered as a presumptive diagnosis in patients with chronic alcoholism, malnutrition, and amino acid imbalance in industrialized countries, even if they exhibit only neurological symptoms .
In conclusion, it is emphasized that all physicians should be suspicious of photosensitivity dermatoses in alcoholics (pellagra may be masquerading), and treat them with multiple vitamin therapy, including nicotinic acid.
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