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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 3  |  Issue : 2  |  Page : 126-129

Pellagra: A forgotten entity


1 Department of Dermatology, Venereology and Leprology, Gandhi Medical College, Hyderabad, Telangana, India
2 Clinical Division, National Institute of Nutrition (ICMR), Hyderabad, Telangana, India
3 Department of Microbiology and Immunology, National Institute of Nutrition (ICMR), Hyderabad, Telangana, India
4 Division of Public Health Nutrition, National Institute of Nutrition (ICMR), Hyderabad, Telangana, India

Date of Web Publication15-Jul-2019

Correspondence Address:
Amruth Rao Parveda
Clinical Division, National Institute of Nutrition, Jamai Osmania, Hyderabad - 500 007, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CDR.CDR_23_18

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  Abstract 


Background: Pellagra is due to deficiency of niacin or its precursor tryptophan and is characterized by four Ds: The Dermatitis, Dementia, Diarrhea, and eventually Death if it is untreated. Not long ago, the disease was endemic in several parts of the world; including India. Over the past two decades, only a few pellagra cases have been reported. By the year 2011, Pellagra had almost disappeared due to public distribution system but, the clinical features still prevail in the Indian subcontinent to some extent. Objective: The study was carried out to report our experience with pellagra in a tertiary care hospital. Materials and Methods: We undertook a retrospective study of 335 clinically diagnosed pellagra cases attending the Nutrition Unit of tertiary care hospital from 1992 to 2012. Results: In a total of 335 patients of pellagra studied, there were 316 males and 17 females. Majority of patients were in 30–40 years with mean age 42.76 ± 11.6 years. Chronic energy deficiency was seen in 63.8% of patients. Chronic alcoholism and tuberculosis were noted in 3.88% and 1.19% of patients, respectively. Conclusion: Pellagra is a complex and multisystem disease that occurs due to varied etiological factors. Of these, inadequate diet is the best-recognized cause in the developing countries like India. This study clearly recommends that general ration should be regularly distributed, especially in areas where maize and sorghum are cultivated and consumed.

Keywords: Dermatitis, isoniazid, niacin, pellagra


How to cite this article:
Brahmaiah U, Parveda AR, Hemalatha R, Laxmaiah A. Pellagra: A forgotten entity. Clin Dermatol Rev 2019;3:126-9

How to cite this URL:
Brahmaiah U, Parveda AR, Hemalatha R, Laxmaiah A. Pellagra: A forgotten entity. Clin Dermatol Rev [serial online] 2019 [cited 2019 Aug 23];3:126-9. Available from: http://www.cdriadvlkn.org/text.asp?2019/3/2/126/262775




  Introduction Top


Pellagra is a disorder that usually occurs due to deficiency of niacin or its precursor tryptophan. The name pellagra is derived from the Italian word “pelle” signifying “skin” and “agra” meaning “rough.”[1] It is a clinical syndrome characterized by a photo distributed rash developing into a chronic dermatitis, gastrointestinal manifestations and neurologic and psychiatric disturbances and traditionally these symptoms remembered as classic four Ds: the Dermatitis, Diarrhea, Dementia, and rarely Death if it is untreated.[2],[3],[4]

Until the late 1950s, pellagra was considered as endemic. With the increase of population and the scarcity of availability of food, lack of proper sources of Vitamin B3 (nicotinic acid) led to the occurrence of pellagra. Research reports revealed that people who consumed millet jowar (sorghum) as their staple diet were more prone to pellagra. The high leucine content in millet decreases the absorption of nicotinic acid.[5] After the Green Revolution in the late 1960s, there has been a significant decrease in the prices of rice and wheat in the country. They became affordable to the common man, and once they started consuming rice, the incidence and prevalence of pellagra started to decrease.[6]

In the developed countries, pellagra has almost disappeared but, the clinical features of the condition remain poorly characterized.[3] In India, it is commonly seen in low socioeconomic group of population and generally affects adults. Pellagra is now considered to be a multifactorial disease.[7] Although rare in developed countries due to niacin fortification of food it is seen among individuals with malnutrition,[8] chronic alcoholism,[9] anorexia nervosa[10],[11] Hartnup disease,[12] HIV infection,[13],[14] and atopic dermatitis with dietary restriction.[15]

Pellagra can also be seen in gastrointestinal diseases showing malabsorption due to niacin deficiency such as Crohn's disease, severe ulcerative colitis, coeliac disease, gastroenterostomy, subtotal gastrectomy, hepatic cirrhosis, intestinal tuberculosis, and malignant gastrointestinal tumors.[8]

In carcinoid syndrome, pellagra occurs due to the excessive conversion of tryptophan to serotonin.[9] Drugs commonly implicated to cause pellagra include isoniazid, pyrazinamide, 6-mercaptopurine, 5-fluorouracil, azathioprine, and phenobarbital.[16],[17],[18]

The present retrospective study aims to report our experience with pellagra in a tertiary care hospital.


  Materials and Methods Top


The case records of patients with clinical diagnosis of pellagra attending the Nutrition Unit of Osmania General Hospital (OGH), Hyderabad, managed by the National Institute of Nutrition (Indian Council of Medical Research) were retrospectively reviewed between 1992 and 2012. The inclusion criteria were as follows: (a) clinical findings consistent with pellagra (photosensitive rash in sun-exposed areas), (b) resolution of symptoms with administration of niacin, and (c) exclusion of other diseases. The medical records were reviewed for age, sex, seasonal variation, cutaneous examination findings, and associated symptoms. Chronic energy deficiency (CED) was calculated based on body mass index (BMI) <18.5 kg/m2.

Statistical analysis

R: A language and environment for statistical computing, Vienna, Austria (Version 3.0) software was used for carrying out data analysis. As this was an observational study, descriptive statistics was carried out. For continuous variables, mean and standard deviation (SD) was calculated. For categorical variables, frequencies were calculated.


  Results Top


A total of 335 patients were included in the study. [Table 1] shows the corresponding descriptive data. Most of the patients were in 30–40 years (33.9%) with mean age of 42.76 years. The mean and SD of BMI of the patients was 17.83 and 3.26, respectively. CED was present in 63.8% of patients. Overweight and obesity were uncommon in the study. The most common age groups affected were middle-aged patients, and the highest was observed in 30–40 years age group followed by 40–50 years of age group [Table 1]. Patients <20 years and >60 years were uncommon in the study. Chronic alcoholism was present in 3.88% of patients, followed by tuberculosis in 1.19% of cases.
Table 1: General characteristics of patients suffering from pellagra in males and females

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Majority of patients had shown bilaterally symmetrical hyperpigmented lesions over dorsa of hands and extensor surface of forearms followed by face and neck. Legs and feet were less commonly involved. Erosions, vesicles, and scaling were seen in few patients.

Peripheral neuritis and anemia were seen in 2% and 1.8% of the patients, respectively, followed by diarrhea, nutritional edema, glossitis, and ascites.

The incidence of cases reported at OGH was common in spring season and was highest in March (10.8%) followed by January (10.5%) [Table 2].
Table 2: Seasonal variation in the pellagra cases

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The number of cases reported was highest in 1992 (32 cases) followed by 1998 (30 cases) and got declined from 2008 onwards [Figure 1].
Figure 1: Time trends in the cases of pellagra attending Osmania general hospital (1992–2012)

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  Discussion Top


Pellagra is due to the deficiency of tryptophan or niacin. The deficiency can be primarily nutritional in origin or secondary to other diseases.[19] Pellagra was eradicated from most parts of the world mainly due to dietary modification. Despite this, few sporadic cases continue to occur. It was the first photosensitive disorder described in the medical literature characterized by dermatitis on the sun-exposed skin with a sharp demarcation line from the unexposed skin. In the beginning, it is erythematous and later becomes dark, dry, and scaly. Lesions on the neck are sharply demarcated resembling a necklace known as “castle's necklace”[8] [Figure 2]. Few patients in our study had shown vesicles indicating an acute onset of pellagra which were resolved with persistent erythema and scaling. In the early phase, pellagra stimulates sunburn where skin erythema and edema is usually fade in few days while in pellagra skin shows prominent hyperpigmentation.[20]
Figure 2: Clinical image showing “Casal's necklace”

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Although pellagra can occur in all ages,[8] our study shows, it was predominantly seen among 30–40 years of age group. The present study shows male predominance (94.3%) when compared to females (5.07%).

As expected in our study, pellagra was more common among CED patients. Pellagra often shows seasonal variation. In the present study, majority of cases were reported in the late winter/spring season which was consistent with other studies.[21],[22]

Niacin is synthesized from dietary tryptophan in the presence of vitamins thiamine and pyridoxine.[4] In the present study, 3.88% of patients had a history of chronic alcohol intake, where thiamine deficiency in alcoholism would contribute to it[16],[23] and it is the potential etiology.[17] About 1.19% of patients diagnosed with tuberculosis were on isoniazid, which was the implicated to cause pellagra.[9],[24] Antituberculotic drug isoniazid may induce a state of pyridoxine deficiency and can suppress the endogenous production of niacin and subsequent pellagra.[8] This can be reversed with pyridoxine supplementation.

Dorsa of hands and extensor surface of forearms were more commonly involved in the majority of patients which was consistent with previous studies.[2],[9] Peripheral neuritis is the most common comorbidity seen in our study which may be due to thiamine deficiency secondary to alcohol intake. About 2% of the patients had shown anemia indicating prolonged nutritional deficiency. This could be the factor for the development of pellagra as iron deficiency reduces the efficacy of niacin synthesis from tryptophan.[25]

The cyclical trend in increase and decrease in cases over the years may be attributed to changing government decisions on free and cheaper rice schemes. As shown in [Figure 1], the number of cases was higher in the earlier years and precipitously declined 2008 onward. This could be due to the introduction of cheaper rice schemes by the government of Andhra Pradesh from 2007. This clearly shows the role of nutrition in the development of pellagra.

As shown in [Figure 3], the consumption pattern of Millets in Andhra Pradesh has shown a decline of 68% (44–14 g) apart from decline in other Indian states.
Figure 3: Time trends in the consumption of Millets (g/CU/day). Source: National Nutrition Monitoring Bureau Technical Report Nos 24 and 26

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The main reason for the sharp decline in the consumption of millets and decline in pellagra cases is the availability of rice and wheat at subsidized rates, under the public distribution system (PDS). Other reasons attributable to the decline include increase in per capita income, growing urbanization, changing tastes, and preferences among the population groups.

Pellagra is to be differentiated from other photosensitive disorders such as systemic lupus erythematosus, photocontact dermatitis, polymorphic light eruption, and pseudoporphyria cutanea tarda.[9] Once pellagra is suspected, physiological doses of niacin should be initiated. In the presence of classical lesions, their swift improvement in the response to niacin is the strongest indicator of diagnosis of pellagra.[3] In our study, all the cases had shown rapid response to niacin supplementation.

Nowadays, classical clinical pattern of pellagra (dermatitis, dementia, and diarrhea) is rare and may present with one or more of these manifestations. However, dermatitis is the most commonly seen clinical presentation,[26] and hence, pellagra is usually diagnosed on dermatological features which are more specific as gastrointestinal and neurological manifestations are varied and nonspecific.

The main drawback of the present study is the lack of biochemical evidence of the nutritional status of the patients. These investigations were not done because of their nonavailability in a resource-poor setup.


  Conclusion Top


Pellagra is a historically old disease, which is not completely eradicated. The decline in the proportion of pellagra patients over the past few decades may be attributed to the implementation of national nutritional programs, PDS, and improved nutritional status. Therefore, nutrition seems to play an important role in the pathogenesis of pellagra.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

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