Pellagra associated reversible dementia

Uvod. Celijakija je oboljenje koje nastaje kao posledica određene nasledne predispozicije, trajna nepodnošljivost glutena, belančevine pšenice, ječma, raži i ovsa. Prve promene kod predisponiranih događaju se na sluzokoži početnog dela tankog creva. Pri tome se smanjuje apsorpcija i javlja se nutritivni deficit. Smanjuje se unos niacina ili triptofana, što je jedan od uzroka nastanka pelagre. Pelagru karakterišu dermatitis, dijareja i demencija. Ukoliko se ne leči, javljaju se dezorijentacija, konfuzija, delirijum i, na kraju, nastupa smrt. Prikaz slučaja. Pacijentkinja starosti 33 godine, zaposlena u fabrici obuće, majka dvoje dece, dolazi u pratnji majke. Majka primetila da je postala nezainteresovana, zaboravna, neraspoložena, ćutljiva, bez inicijative. Od malena boluje od celijačne bolesti i godinama koristi kukuruzni hleb. Od pre mesec dana ima promene na koži i prolive. Razlog dolaska uplašila se jer juče nije znala kako da se vrati kući posle posla. Shvaćena je kao pelagroidna demencija celijačnog porekla zbog nedostatka vitamina B (B1, B2, B3, B6, B12). Nakon intenzivne vitaminske terapije i adekvatne ishrane, preporučene od strane nutricioniste, poremećaj se povukao. Zaključak. Anamneza sa tipičnom slikom je dovoljna da se posumnja na pelagru. Ukoliko znamo da je celijakija razlog uzimanja kukuruznog brašna (u kukuruznom brašnu nema vitamina B) i pojave proliva, pretpostavljamo da je to predispozicija za nastanak pelagre. Nakon dijagnostikovanja celijakije, u lečenje se moraju uključiti gastroenterolog i nutricionista. Ako se pojave komplikacije bolesti, uključuju se dermatovenerolog, infektolog, neurolog i psihijatar. Ključne reči. Demencija, pelagra, celijakija, vitamini grupe B, osnovna zdravstvena zaštita. Abstract


Introduction
Celiac disease or gluten-sensitive enteropathy is precipitated by permanent intolerance of gluten, a protein found in wheat, barley, and rye 1 . Celiac disease is an example of the most common food intolerance. The immune system, in genetically predisposed persons, reacts to gluten intake and leads to damage in the small intestine mucose. An ever-growing number of celiac disease patients is allotted to changes in food habits, early infections affecting digestive tract (especially rotavirus infections), an increased number of caesarian deliveries. 2 Celiac disease is a multifactorial, genetically determined, autoimmune disease. The disease trigger is gluten and similar substances found in grains. There is a varying degree of small intestine mucose damage and a spectrum of clinical symptoms, but all of them are due to malabsorption. It`s a chronic disease found in persons with a genetic predisposition. Its incidence is 1%.
The most common manifestations of the disease are abdominal pain and unease, frequent stool elimination, weight loss, osteoporosis, anemia, general weakness, and exhaustion. 2 The stools are frequent, fatty, excessive, and foul-smelling. Quite often the disease may cause skin eruptions (dermatitis herpetiformis), neurological symptoms, such as muscle weakness, walking disorders, and seizures, different forms of bleeding due to vitamin K malabsorption in the intestines. Celiac disease manifestations vary from osteogenesis disorders, anemia, malignant diseases (mainly of the digestive tract) to cognitive and mental disorders. 3,4,5 The first problems appear in the intestine villi. Due to the gluten effect, the villi shrink until they totally disappear. It leads to severe mucose damage and malabsorption of nutrients and vitamins. Their regeneration won`t occur unless gluten intake is discontinued.
Pellagra is a disease caused by a lack of vitamin B 3 (niacin), essential for all living cells because it is the part of many enzymes and it has many roles in organism functioning. 3 It is an essential factor for the normal metabolism of nerve cells. 4 Over time, doctors noticed that not all cornbread eating patients suffered from pellagra, so they concluded the lack of nicotinamide was the cause of the disease, as well as the change in intestinal bacterial flora. It`s a well known fact, a great number of vitamins are synthesized in the intestines under the influence of gut bacteria (thiamine, riboflavin, biotin, nicotinamide). Clinical presentation of pellagra comes down to dementia, dermatitis, diarrhea.
Depression, delirium, and hallucinations may occur if the disease has not been treated. 5 One of the first signs of trouble is when the doctor notices the patient is unable to participate in a conversation with several other persons. This implies the information reception process is being damaged. Persons with cognitive damage are unable to organize, lose time and space orientation, forget things, can not memorize new events, can not understand a joke, do not own the ability of logical thinking and conclusion making.
The blood levels of antigliadin, tissue transglutaminase, endomysium, and reticulin antibodies in the diseased persons are elevated. To confirm the diagnosis of the celiac disease, small intestine biopsy and serological tests (antibodies) should be performed. Hematologic and serological analyses are of importance, levels of electrolytes, and barium X-ray of the gastrointestinal tract.
If the patient has already been diagnosed with celiac disease, in order to prevent pellagra/vitamin deficiency, he should be advised about the change in his nutritional habits (avoid gluten containing foods and use vitamin supplements all their lives).

Case report
Female patient, 33, works in a shoe factory, mother of two, presents with her mother for her first psychiatric appointment.
Her chief complaint was that she couldn`t remember how to get back home from work, on her own, the previous day. She usually goes to and from work with her neighbor, but the neighbor had to leave work earlier that day… Heteroanamnestic data: Her mother noticed that she has become forgetful, absent, disinterested, silent, with no initiative, moody, since last month. Her condition deteriorated gradually. She noticed itchy red patches on her face, hands, and blisters started appearing as well. She considers skin lesions consequence of her working environment (works in a shoe factory, possible allergy to glue, leather, dirt, solvents, colors,..). For a month she has been suffering from excessive diarrheas, which are watery and foul-smelling. She has no appetite and lost over six kilos. She complained of an upset stomach.
Personal history. She has been suffering from celiac disease since childhood, eats only cornbread, doesn`t make regular appointments with her internist, doesn`t remember when she did her lab tests, and she never consulted a nutritionist.
General status: skinny, dehydrated, tongue smooth, red; simetrical skin lesions on the exposed parts of the skin (palms, forearms, neck) in the form of partly desquamated epidermis and vesiculobullose lesions on the erythematous base.
Neurological status: discret tremor of the outstreched fingers, positive Romberg test, wide-based gait. A neurologist performed a lumbar punction, suspecting encephalitis, but CSF was sterile.
Psychological status: conscious, verbal communication possible, but not in depth; disoriented in time, unsure in space orientation. She says she`s not quite sure where she`s at and wouldn`t be able to find her way home on her own. Thinking concrete, cognitive-amnestic functions impaired, intellectual capacity lowered. Impaired memory for new and old events. Obvious fall in voluntary-instinctive dynamisms, psychomotor slowing, decline in concentration, inability to calculate, and make a logical deduction. Social retreat and apathy.
CT of the head was planned, but wasn`t performed due to the technical problems.
Due to excessive cognitive decline and mood disorder, we asked for the opinion of the social worker (from the factory the patient was working at). The social worker said she noticed the changes in the patient in the last few years, especially since her husband left the family. In the beginning, they thought she was depressed and she was sent on sick leave and recreational retreats, but she couldn`t keep pace, she was slow, started losing concentration, often made mistakes. She was assigned to pack shoes into boxes, but she failed at it as well.
Lately, she has been showing conspicuous behavior, she was apathetic, slow, confused, neglected.
Based on the clinical presentation, history, and lab results we diagnosed pellagra induced dementia in celiac disease (F02.8, E52 -cause) and give adequate therapy.
The diagnosis was confirmed with additional lab findings: low level of tryptophan, niacin, and pyridone in the urine. An internist was consulted and he prescribed adequate therapy.

Conclusion
Pellagra is a potentially deadly disease, and it often includes symptoms such as skin lesions, mental disorders, and indigestion. It is often found in people living in the poor, rural areas, especially in those who mainly use corn. Pellagra is a clinical syndrome appearing due to the lack of niacin (PP vitamin or B 3 vitamin). It occurs only if the intake of essential amino acid tryptophan is insufficient. Tryptophan is necessary for niacin synthesis. Unfortunately, even though it`s easy to prevent and treat with proper nutrition (animal-based proteins -milk, meat..) it still takes away a lot of lives worldwide.
Preventive measures include, among other things, people`s education on healthy nutrition. If cornbread is being used, then animal-based proteins should be included, along with fresh fruits and vegetables.
Vitamin supplementation should be regular in order to avoid mental problems.
The most important thing in the treatment of celiac disease is to eat properly and exclude gluten. A gluten-free diet is lifelong and it affects the quality of life tremendously. It`s very difficult to find the foods which are completely glutenfree and in some patients this diet is not very favorable.