Pellagra: a rare complication of anorexia nervosa
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- Jagielska, G., Tomaszewicz-Libudzic, C. & Brzozowska, A. Eur Child Adolesc Psychiatry (2007) 16: 417. doi:10.1007/s00787-007-0613-4
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Pellagra is a potentially fatal, nutritional disease with cutaneous, gastrointestinal, and neuropsychiatric manifestations. Because of the diversity of pellagra’s signs and symptoms, diagnosis is difficult without an appropriate index of suspicion. A case of pellagra in a 14-year-old girl with anorexia nervosa is presented. Signs and symptoms of pellagra were resolved after niacin therapy and dietary treatment.
Anorexia nervosa (AN) is a chronic, life-threatening eating disorder that leads to many somatic complications [2, 5, 8]. Severely restricted diets may result in nutritional deficiency, hypo- or avitaminosis. A long lasting low fat diet may lead to fat-soluble vitamin deficiency. Similarly a protein free diet may cause hypoproteinemia and essential amino acid depletion.
In the course of AN cutaneous symptoms frequently appear, and sometimes they may even lead to the diagnosis of an occult eating disorder . The most common abnormalities include: dry, rough and hypercarotenemic skin, desquamation, keratosis pilaris, hyperpigmentation of body hair and lanugo [2, 5]. Dietary change or starvation lead, in order of frequency, to: xerosis, lanugo-like body hair, telogen effluvium, carotenoderma, acne, hyperpigmentation, seborrheic dermatitis, acrocyanosis, perniosis, petechiae, livedo raticularis, interdigital intertrigo, paronychia, generalised pruritis, acquired striae distensae, slower wound healing, prurigo pigmentosa, oedema, linear erythema craquele, acral coldness, pellagra and scurvy and other miscellaneous conditions .
Pellagra is a rare, potentially fatal complication of AN that results from a deficiency in dietary niacin (vitamin PP) and its precursor, the essential amino acid tryptophan. Niacin-deficient diets are protein free and relatively high in carbohydrates. Endemic focuses of pellagra are located in Africa, Mexico, Indonesia and China. A majority of patients with clinical pellagra in modern societies are poor, homeless, alcohol dependent people or psychiatric patients who refuse food. Other risk factors, such as mycotoxins, excessive dietary leucine intake, carcinoid syndrome, estrogens and progestogens, isoniazide therapy, and impaired assimilation of niacin or tryptophan in malabsorption states, may also lead to the development of pellagra [4, 6].
Skin manifestations of pellagra usually precede other symptoms, and may present as sunburn-like erythema with bullae, or more typically as hyperpigmentation and desquamation of sun-exposed sites . The disease should be considered in the work-up of patients who exhibit cutaneous manifestations subsequent to sunlight exposure. The photosensivity is of a phototoxic origin. Epidermal repair processes after ultraviolet light-induced injury are reduced due to deficient diphosphopyridine and triphosphopyridine nucleotide synthesis that is tryptophan-dependent .
The first sign of classic pellagra is anorexia, the most pathognomonic is photosensitive dermatitis, but nowadays, undiagnosed subclinical forms of the disease are more likely to occur, because of general improvement of diet. Cleary and Cleary  even suggested that AN is a form of subclinical pellagra.
Dermatitis, alopecia, oedema
Loss of appetite, achlorhydria, cheilitis, stomatitis, nausea, vomiting, constipation
Ataxia, paralysis of extremities, peripheral neuritis
Anxiety, depression, delirium, psychotic symptoms, intermittent stupor, incoherent train of thoughts, fatigue
Vague somatic complaints
Psycho-sensory disturbances (impressions as being painful, annoying bright lights, odours intolerance causing nausea and vomiting, dizziness after sudden movements)
Psycho-motor disturbances (restlessness, tense and a desire to quarrel, increased preparedness for motor action)
Weakness and increased fatigability
Headaches (occur suddenly with nausea and vomiting)
Differential diagnosis of pellagra and anorexia nervosa
Sunborn-like erythema with bullae or hyperpigmentation and desquamation of sun-exposed sites
Dry, rough skin with desquamation and keratosis pilaris, hyperpigmentation of body hair and lanugo
Glossitis, stomatitis, cheilitis
Absent/present in patients which misuse of laxatives
Ataxia, paralysis of extremities
Emotional disturbances (depression, anxiety, fatigue, irritability)
Sporadically in cases with severe life-threading biochemical complications
Psychotic symptoms, intermittent stupor, incoherent train of thoughts
Absent/delusional beliefs concerning body image and diet
In our case the symptoms of pellagra occurred in a 14-year-old patient with AN who was on an extremely restricted diet.
A 14-year-old girl with a diagnosis of AN based on DSM-IV criteria was admitted to The Child and Adolescent Psychiatry Department of The Medical University of Warsaw in August 2003 with 45.9% weight loss. Her premorbid BMI has been 23.98 kg/m2.
During the six months before admission she had been on an extremely restricted, low calorie diet and for the last three months she had been eating only fruit (a calorie intake of not more than 300 kcal/day).
Two months before the admission she had become irritable, sad and weepy. She had been mentally and physically drained, had complained of insomnia and early morning wakening. Significant psychomotor retardation and depressed mood had been noticeable. She was preoccupied by dieting ideas, felt hungry but was afraid of putting on weight.
On physical examination at admission cachexia (BMI = 13.41 kg/m2), hypothermia (36.0°C), arterial hypotension (85/50 mmHg), bradycardia (HR-48/min), arrhythmia, low apex murmur, massive peripheral oedema and cyanosis were present. Erythema and desquamation of the skin were located on forearms, elbows and the nape of the neck. In the pretibial area some scratches and petechiae were observed. Stomatitis was also present, the abdomen was tender to palpation, peritoneal signs were negative, peristaltic movements were distinct. The liver was enlarged, palpable 2 cm below the costal margin.
The patient complained of being easily fatigued, dizziness, diminished concentration, a burning sensation in the eyeballs, palpitations, muscle cramps in the calves and abdominal pain.
On admission laboratory tests showed: leucopoenia (3,100/mm3), haemoglobin −11.2 g%, glucopoenia (serum glucose-55 mg%), a decreased level of serum triglycerides (TG-29 mg%). Other parameters of blood cell count; proteinogram, lipidogram and transaminases were within normal range. Antinuclear antibodies were negative. Electrolyte levels were normal. Ultrasonography of the abdomen and the pelvis revealed a peritoneal effusion in the Douglas’s cavity. Two weeks later a trace amount of the effusion was still present. An ECG showed sinus bradycardia (heart rate 45–50/min), low voltages of all waves, significant non-specific ST-T changes. In an ECG made after a month of treatment sinus rhythm 90/min, low voltages of all waves, non-specific ST-T wave changes were present. In echocardiography (ECHO-2D) pericardial effusion 4–5 mm thick by the right and the left ventricle and 10 mm thick by the left atrium without any hemodynamic symptoms was present. 1st degree tricuspid valve insufficiency and trace mitral valve insufficiency were found. The structure of the heart muscle was normal. An ECHO made five weeks later showed pericardial effusion up to 3 mm thick by the right atrium and a trace of effusion by the left ventricle.
A diagnosis of AN with cardiovascular complications and pellagra was made.
Due to intense abdominal pain and chronic diarrhoea on the day after admission complete intravenous nutrition was administered and was continued for the next 11 days. Oral feeding was introduced gradually. In the first week of inpatient treatment she lost 2.5 kg, due to a reduction of the peripheral oedema. Later on, a weight gain of approximately 1.4 kg per week was observed. The patient was treated with niacin 100 mg daily for 14 days. The stools became normal after 10 days of the niacin therapy. The cutaneous changes diminished within several days and disappeared within 25 days of the treatment. Regression of the pretibial oedema and petechiae was observed after two weeks. All abnormal parameters (except ECG changes) were brought back to normal. Bradycardia disappeared after one month, and EKG normalisation occurred after 10 weeks of treatment. Four days before discharge echocardiography (ECHO-2D) showed trace of effusion in pericardium and normal structure of heart muscle without insufficiency of tricuspid and mitral valve.
The patient was discharged without any complaints and symptoms with BMI = 19.83 kg/m2 after 72 days of inpatient treatment.
This report describes pellagra in a girl with AN. The final diagnosis of pellagra was based on clinical presentation and resolution of cutaneous, gastrointestinal, and psychiatric symptoms after niacin therapy. A standard textbook recommends diagnosis established on clinical assessment and response to therapy because most postulated laboratory indicators, including urinary nicotinamide and serum niacin levels, have not proved reliable [7, 10].
In the absence of definitive laboratory results, this report relied on clinical diagnosis. In this case dermatitis, diarrhoea, sporadic vomiting, massive oedema were present. However, differential diagnosis is difficult. Many other symptoms observed in our patient (hypothermia, bradycardia, arterial hypotension, peripheral oedema and acrocyanosis, leukopoenia, decreased haemoglobin, glucopoenia, changes in EKG and echocardiography, pericardial and peritoneal effusion as well as psychological symptoms and symptoms of CNS ) are common complications in AN arising from emaciation.
In the cases described previously [3, 4, 6] two patients exhibited cutaneous manifestations subsequent to sunlight exposure [4, 6], in one of them the sunburn reaction occurred after exposure to a sunlamp for tanning . In one case  dermatitis was absent but stomatitis, glossitis and psychotic symptoms were observed. In all cases the signs and symptoms of pellagra resolved after institution of niacin therapy and dietary treatment.
This case highlights a rare, but serious medical problem of pellagra in AN.
This fatal but easily treated disease may be readily overlooked because of its rarity. Anorexia nervosa, especially with severe dietary restrictions appears to identify a group at special risk of pellagra. The appropriate diagnosis of pellagra in AN patients is quite difficult, because of the overlap of symptoms of pellagra and starvation. Special attention should be paid to cutaneous symptoms in anorexia patients, especially to photosensitive dermatitis.
This work was supported by grant 2M7/N/2005 from The Medical University of Warszaw.