Pellagroid dermatitis during a ketogenic diet and anti-epileptic therapy

ARTICLE

Auteur(s) : Annalisa Patrizi¹, Federica Bianchi¹, Liliana Volpi², Carlo Lesi³, Luciana Andrini³, Elisabetta Fantoni³, Iria Neri¹

¹Department of Internal Medicine, Geriatrics and Nephrology, Bologna University, via Massarenti 1, 40138 Bologna, Italy
²Department of Neurosciences, Bellaria Hospital, Bologna, Italy
³Clinical Nutrition Unit, Bellaria Hospital, Bologna, Italy

Pellagra is a nutritional disorder characterized by the well-known group of symptoms called “Pellagra's four D”: dermatitis, diarrhea, dementia and, when untreated, death.

The main cause of pellagra is niacin and tryptophan deficiency. Niacin is a vitamin taken directly from the diet or synthetized from dietary tryptophan in the presence of vitamins B2 and B6. Accordingly, a deficiency of one of these two vitamins may cause pellagra. Nicotinamide or vitamin PP (Pellagra Preventive factor) is a natural derivative of niacin.

A 20-year-old boy referred to our Neurological Department at age 12 because of an intractable epilepsy. Neurological examination showed severe psychomotor delay, tetraparesis, facial dysmorphisms, mycrocephaly, nystagmus, trunk hypotonia, limb hypertonia and growth deficiency. Metabolic investigations and caryotype were normal, FRAXA mutation was absent. Because of his catastrophic epilepsy, when he was 12.9 years old, a ketogenic diet was added to the anti-epileptic treatment (valproate 900 mg/day; ethosuximide 750 mg/day; gamma vinyl-gamma-aminobutyric acid 1,000 mg/day), with excellent results. Consequently, valproate was decreased to 700 mg/day while the other drugs remained unchanged.

Two years and 7 months after the ketogenic diet was started and about 6 weeks after the family had stopped the multivitamin and oligoelement supplements, considered unnecessary, without medical advice, the boy, aged 15.4 years, developed a diffuse desquamating dermatitis, mainly in photo-exposed areas. Sharply demarcated, brown-red plaques with a rim of exfoliation were present on the dorsal surfaces of both hands, around the elbows and knees, on the V of the neck and on the face (figure 1). The patient did not have diarrhea nor adnexal nor mucosal lesions, in particular, he did not have stomatitis.

Blood biochemical values, including inflammation indexes, lymphocyte subpopulations, total and specific IgE for food and inhalant allergens were normal. Retinol binding protein was mildly reduced (2.7 mcg/mL) and vitamin PP level was significantly decreased (< 1 mcg/mL). A diagnosis of pellagra-like dermatitis, as the only sign of the “four D syndrome”, was made. Nicotinamide, B vitamins, zinc and magnesium supplements were started, as well as the use of emollients and total sunscreens. Anti-epileptic drugs (AEDs) remained unchanged. After 4 weeks the dermatitis was markedly improved, and 5 months later the patient had post-inflammatory hyperpigmentations and a normal vitamin PP level.

Pellagra is characterized by a symmetric erythematous and desquamative dermatitis, with marked photosensitivity. Mucous membrane signs include cheilitis and glossitis. Pellagroid eruptions have been related to malabsorption, anorexia, chronic alcoholism, metabolic derangements and several drugs, including AEDs such as carbamazepine, phenobarbital, valproic acid, phenytoin, ethosuximide, sometimes during combined anti-epileptic therapy, and with normal nicotinamide and vitamin B6 levels [1-4]. To our knowledge, only one pediatric case has been reported [2]. The mechanism by which AEDs may cause pellagroid eruptions is unclear, concomitant nutritional or gastrointestinal absorption disorders have been reported and AEDs may also cause dysregulation of group B vitamins and tryptophan metabolism, even during long term therapies [1, 4].

The ketogenic diet is a dietary therapy used for drug-resistant epilepsies of childhood, characterized by high fats, low carbohydrates, adequate proteins and calories and requiring supplements to avoid vitamin and oligoelement deficits. The mechanism by which the ketogenic diet improves seizure control is still debated [5]. This dietary therapy needs careful monitoring because of a few potentially serious side effects, including kidney stones, slowed growth, osteopenia, iron-deficiency and anemia, and possible interactions with AEDs [6].

As far as we know, our case is the first pellagroid skin eruption related to a vitamin PP deficit due to the stopping of supplements during ketogenic diet and anti-epileptic therapy, and emphasizes that an appropriate supplementation of vitamins and oligoelements is mandatory in such cases.

Disclosure

References

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3 Spivak JL, Jackson DL. Pellagra: an analysis of 18 patients and a review of the literature. John Hopkins Med J 1977; 140: 295-309.

4 Lyon VB, Fairley JA. Anticonvulsant-induced pellagra. J Am Acad Dermatol 2002; 46: 597-9.

5 Stadler R, Orfanos CE, Immel C. Drug-induced pellagra. Hautarzt 1982; 33: 276-80.

6 Freeman J, Veggiotti P, Lanzi G, Tagliabue A, Perucca E. The ketogenic diet: from molecular mechanisms to clinical effects. Epilepsy Res 2006; 68: 145-80.