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Pellagra- Clinical Case Discussion (Niacin/Vitamin B3 Deficiency)

Clinical Presentation of Pellagra

Imagine a 20-year old patient presents to you with a history of symmetrical, bilateral cutaneous skin lesions mainly involving the sun-exposed areas including the dorsum of the hand, feet, neck and the face for 6-8 weeks duration. Initially, the rash has been merely a redness in the skin which has progressed into cracks with occasional ulceration. Some skin areas have become thickened, dry and pigmented as well.

Apart from the skin lesions, the patient also complains of diarrhea, nausea, poor appetite and difficulty in chewing food and swallowing. The patient looks a bit emaciated as well.

What could be this patient’s medical condition? Truth be told, these symptoms could be due to a wide spectrum of disease conditions. It is better to develop a list of possible diagnoses in mind so that you can narrow it down later with the method of exclusion.

Differential Diagnosis (DDx) You Should have in Mind

DDx:

But after analyzing the initial symptoms, it is difficult to arrive at a definitive diagnosis straight away. But given the patient’s malnourished state it could be some form of nutritional deficiency. We need examination and investigation findings to come to a final diagnosis.

Before, going into the clinical findings and investigations of our patient, let’s have a look at the details of pellagra as to what it truly is and how it develops as a medical condition.

What is Pellagra?

Pellagra is a very rare nutritional disorder that occurs due to niacin or vitamin B3 deficiency in the body.

Pellagra is commonly found in individuals who eat only untreated maize, especially in developing countries in Africa. Maize contains niacin but in an inactive, less biologically available form of niacytin. It also has a very low content of tryptophan.

In regions of the world where people consume untreated maize as their staple food item, coupled with other nutritional deficiencies, pellagra can be a common finding.

On the other hand, in regions like Central America, this condition is quite rare because those people usually soak maize overnight with calcium hydroxide before making food items like tortillas allowing the release of niacin in its active form.

Importance of Niacin

Niacin or vitamin B3 is the generic name for the two chemical forms of nicotinic acid and nicotinamide. It is found in many food sources including plants, meat and fish.

Nicotinamide contributes to forming nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).

Both molecules play important roles in energy-generating reactions in the body for the production of ATP molecules. In oxidative reactions, they act as hydrogen acceptors. On the other hand, in their reduced forms as NADH and NADPH, they play the role of hydrogen donors for reductive reactions.

Niacin is readily produced inside the human body with the help of an amino acid called tryptophan. Food sources like eggs and cheese also contain tryptophan. Tryptophan can be converted to niacin at the ratio of 60 mg of tryptophan to 1 mg niacin inside the body.

The conversion of tryptophan to niacin is regulated by two enzymes called Kynureninase and Kynurenine hydroxylase. Both these enzymatic reactions depend on vitamin B6 and riboflavin. Therefore, deficiency of other vitamin B forms can also lead to pellagra.

Common causes for Primary Pellagra

Common causes for Secondary Pellagra

The Classical Triad of Symptoms in Pellagra

Usually, Pellagra presents with a triad of three classical symptoms. However, not all the symptoms occur at every instance.

Initially, the lesions start with redness that gradually develops into cracks and occasional ulceration. When the lesions are limited to the neck areas usually hidden by clothes, the condition is known as Casa’s necklace or collar.

With time, chronic thickening, dryness and pigmentation of the skin can occur.

Findings you should elicit on clinical examination

What are the investigations you should order?

Can include the basic investigations to assess the overall health status of the patient;

The specific investigations that you can order include;

How can you arrive at a diagnosis?

In a limited-resource clinical setting, the diagnosis of pellagra is mainly a clinical one. In such a situation, it is important to take other nutritional deficiencies that may give a similar clinical picture into consideration as well.

HPLC of urine for niacin metabolites gives the most sensitive results out of all the tests available.

In the case of pellagra, the serum niacin, tryptophan, NAD and NADP levels will be low. They indirectly assess the dietary intake of niacin. Usually, these tests are performed to confirm the clinical suspicion of pellagra where appropriate. However, if the niacin deficiency is short-lived, these tests may not reveal accurate results.

At the acute stage of the disease, histological findings may reveal infiltration of the epidermis with neutrophils, intra/subepidermal vesicle formation or intracellular edema. Chronic lesions may manifest hyperkeratosis, increased basal layer melanin, parakeratosis and acanthosis.

How can you manage an acute case of Pellagra?

Pharmacological Management

Oral nicotinamide therapy (approximately 300mg daily with a maintenance dose of 50mg daily(1)) often paves the way for significant improvements in the skin condition and diarrhoea within a short duration.

However, as niacin deficiency often accompanies other forms of nutritional deficiencies, the vitamin-B complex is given concurrently.

Especially, when treating alcohol-dependent individuals with thiamine or pyridoxine therapy, it is important to include niacin as well. This is mainly because giving either thiamine or pyridoxine therapy alone without niacin may trigger alcoholic pellagra encephalopathy(2).

Diet

To replenish the deficiency of niacin in the body, consuming food items naturally rich in niacin and proteins is important. Good sources of niacin include green-leafy vegetables, baker’s yeast, milk, fish, meat, and coffee/tea. It is important to increase the diversity of food production, rather than consuming a single source of food like maize.

Although, in normal food preparation, niacin does not get destroyed due to heat, acid or any other method, it is necessary to carry out special food processing and preparation methods to increase the bio-availability of niacin in regular food sources.

For example, fermentation with yeast will increase the vitamin levels, protein contents and mineral bioavailability while improving the quality and digestibility of the food sources.

Similarly, germination for sprouting of cereals and legumes by soaking in water is another way to enhance the nutritional value by increasing the bioavailability of vitamins like niacin, riboflavin and vitamin-C.

Physical Exercise

Bed rest is recommended for severe cases of pellagra. Besides, even for milder cases, it is advised to minimize activities outdoors as exposure to the sunlight may aggravate the skin lesions of pellagra.

How can we manage a Pellagra patient in the long-term?

It is important to prevent the occurrence of niacin deficiency in the future via continuous supplementation.

Niacin Supplementation

It is recommended to have an average intake of about 15–20 mg of niacin per person daily for all age groups to prevent pellagra.(3) It is not practical to consume large amounts of niacin as it is a water-soluble vitamin, it is not stored within the body. The right thing to do is to maintain an adequate daily intake.

Food fortification with Niacin

Several countries add niacin and other nutrients to cereals products and their preparations including rice, maize, corn, bread and pasta products. The main objectives of food fortification are five folds. They include;

Niacin Toxicity

Too much of anything can cause troubles; the same goes for niacin therapy as well. However, niacin toxicity is extremely rare. Sometimes with relatively higher clinical doses of niacin, a few side effects may occur.

They may include;

Severe symptoms of toxicity like jaundice, fatigue, or, rarely, fulminant liver failure may occur in patients having a dose of 1000 mg or more per day of nicotinic acid. It is necessary to seek medical attention as soon as possible when such symptoms of toxicity occur.

What would be the prognosis of our Pellagra patient?

Administration of niacin has a curative effect on pellagra. The treatment with the daily recommended dose of nicotinamide (300mg daily in divided doses) for 3-4 weeks should be carried out for the best results.

Usually, the acute symptoms like diarrhoea, acute inflammation of the tongue and mouth may subside within a few days. Within the first week of therapy, dermatitis and dementia may improve.

Chronic cases of pellagra usually require a longer duration to improve. However, even then, appetite and general physical health may improve quite rapidly.

Conclusion

So, here’s the gist of our discussion. Although it is easy to miss the possibility of nutritional deficiencies when diagnosing a medical condition, you should never rule out them too early, no matter how rare that condition might be!  The thing about vitamin deficiencies is that they usually come in bundles. If malnourishment is the reason behind, there is a good chance that there could be some other nutrients that the patient might be lacking. Therefore, it is important to treat the patient as a whole so as to address every problematic aspect and not just a single component.

References

1.         Kumar and Clark’s Clinical Medicine – 9th Edition [Internet]. [cited 2021 Feb 13]. Available from: https://www.elsevier.com/books/kumar-and-clarks-clinical-medicine/kumar/978-0-7020-6601-6

2.         SERDARU M, HAUSSER-HAUW C, LAPLANE D, BUGE A, CASTAIGNE P, GOULON M, et al. THE CLINICAL SPECTRUM OF ALCOHOLIC PELLAGRA ENCEPHALOPATHY: A RETROSPECTIVE ANALYSIS OF 22 CASES STUDIED PATHOLOGICALLY. Brain [Internet]. 1988 Aug 1 [cited 2021 Mar 28];111(4):829–42. Available from: https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/111.4.829

3.         PELLAGRA and its prevention and control in major emergencies. https://www.who.int/nutrition/publications/en/pellagra_prevention_control.pdf

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