Dermatologic Manifestations of Pellagra Clinical Presentation

Dietary history, the 3 identifying factors (ie, diarrhea, dermatitis, dementia), localization (see Physical below), and seasonal appearance all contribute to the diagnosis. Note the following:

• Early symptoms of pellagra include lassitude, weakness, loss of appetite, mild digestive disturbances, and psychiatric or emotional distress (eg, anxiety, irritability, depression).
• Characteristic and pathognomonic skin changes are usually preceded by prodromal symptoms, especially those of the digestive system.
• The classic triad is dermatitis, diarrhea, and dementia, not invariably appearing in this order.
• The diagnosis of pellagra is difficult in the absence of cutaneous findings.
• Skin lesions (pellagrodermas) are painful on sites of early erythema.
• Burning sensations, headache, and weakness may occur.
• Itching is never present.

Early cutaneous findings

In the first stage, acute pellagra resembles sunburn. The skin is red, and large blebs or blisters that may develop often exfoliate, leaving large areas of denuded epithelium that may resemble severe sunburn. The changes subside, leaving a dusky, brown-red coloration. Tanning occurs more slowly than is typical in sunburn, and exacerbation occurs after reexposure to sunlight.^{[3, 15, 16]}

The eruption usually begins as an acute dermatitis with edema and exudative alterations, changing to an erythema on the dorsa of the hands, with pruritus and burning. Vasomotor changes of cyanosis or bleaching may be well defined, with profuse sweating and a sensation of coolness. Initial bright erythema may change to cinnamon brown in color. Characteristically, the rash is symmetric.

Blisters appear several days after the onset of erythema in some patients. The blisters may coalesce into bullae and then break. In other patients, dry brown scales and blackish crusts, resulting from hemorrhage, form after 2-4 weeks.

Redness and superficial scaling appear on areas exposed to sunlight, heat, friction, or pressure.

Late cutaneous findings

In the second stage, dermatosis becomes hard, rough, cracked, blackish, and brittle. The skin may look like that of a goose, hence the term goose skin. Patients have thickened skin that is dry, scaly, and hyperkeratotic with a parchmentlike appearance and a yellowish brown hue. The skin is darkly pigmented.

When the deficiency state is far advanced, the skin becomes progressively harder, drier, more cracked, and covered with scales and blackish crusts resulting from hemorrhages. Healing usually takes place centrifugally, with the line of demarcation remaining actively inflamed after the center of the lesion has desquamated.

Blisters are present when pellagra recurs at the same site (pemphigus pellagrosus), and they contain lymphocytes, segmented leukocytes, and histiocytes. Occasionally, pustules, crusts, and deep fissures are present.

Localization

Pellagra can affect any part of the body surface, but it more frequently appears in certain areas. The usual sites are the dorsal surfaces of the hands, face, neck, arms, and feet.^[17] The changes are rarely seen elsewhere.

Hands

The backs of the hands are the most common sites for the lesions (in 77-97% of cases), with accentuation of the radial border of the dorsal aspect. Lesions may extend up the arm in the glove or gauntlet form of pellagra. The epidermis of the fingers thickens, and the articular folds disappear. Painful fissures develop on the palms and digits.

Face

Dermatitis tends to follow the distribution of the trigeminal nerve, and the skin is invariably pigmented. A symmetric butterfly eruption is frequently observed; this appearance is similar to that of lupus erythematosus. A characteristic well-marginated eruption often appears on the front of the neck (ie, Casal necklace). Compared with scales elsewhere, scales on the face are thicker and larger and frequently become pustular.

The symmetry and clear line of demarcation from unaffected skin are especially striking. Lesions tend to spread from the sides to the rest of the nose; forehead; cheeks; chin; lips; and, more rarely, eyelids and ears. On the forehead, a narrow border of unaffected skin always appears between the erythema and the hair. Facial lesions never appear independent of lesions on the hands and elsewhere.

Neck

The Casal necklace extends as a fairly broad band or collar around the entire neck (cervical dermatoma with C3 and C4 innervation).

If the band is incomplete, the symmetry of the lesions is striking. The upper border extends anteriorly, somewhat below the hairline to the larynx. The lower border begins under the vertebra prominens and extends to the edge of the manubrium sterni (appendix fasciolae).

In many instances, the necklace has an anterior continuation, or broad cravat, extending from the manubrium over the sternum to the level of the nipples and ending in a point or square. On the back, the border may reach the level of the scapulae.

Affected men, women, and children have the necklace; it is always accompanied by characteristic dermatitis elsewhere.

Feet

Lesions usually do not extend proximal to the malleoli, which are included and may be covered with hyperkeratotic erythema. The heels remain free of lesions. Distally, the eruption ends at the toes or on the backs of the great toes. The front and back of the leg may be involved to form a boot. On the palms and soles, skin may be yellowish, dry, rough, and scaly. In children, the palms and soles are frequently erythematous and rough.

Other sites

The shoulders, elbows, forearms, and knees are occasionally affected. Asymmetric lesions may appear at sites of old injury or stasis.

Nails

Changes are not pathognomonic. Nails are soft, crumbly, and dull. Occasionally, transversal lines are present.

Eyes

Keratoconjunctivitis and keratomalacia may occur.

Mucosal surface of the GI tract

In one third of patients, the lips, tongue, and oral mucous membranes are involved. Highly seasoned or acidic foods can cause mucous membrane inflammation and aggravate tongue and mouth soreness. Typical changes of the tongue and mucous membranes include inflammation and edema of the tongue apex and edges. The tongue is hypertrophic, with pseudomembranous furs, erosions, and ulcers; later, the tongue becomes atrophic.

Other clinical findings include cheilosis, angular stomatitis, and thrush. Bleeding from the gingiva occurs without hemorrhages (hemorrhages occur in scurvy). The lips are inflamed, rough, achy, and shiny.

GI tract

GI tract disturbances can cause poor appetite, nausea, vomiting, epigastric discomfort, abdominal pain, and increased salivation. Diarrhea, gastritis, low levels of duodenal enzymes, and achlorhydria occur in almost 50% of patients.^[16]

Atrophic changes of the gastric mucosa are demonstrated on radiographs. Glossitis causes soreness of the mouth and dysphagia. Anorexia and malabsorptive diarrhea lead to a state of malnutrition and cachexia. Diarrhea results from diffuse involvement of the mucosal surface of the GI tract. Typically, stools are watery, but occasionally, they can be bloody and mucoid.

Neuropsychiatric manifestations

In mild instances, mental disturbances may be unnoticed, and patients may be slightly depressed or apathetic.^[18] Neuropsychiatric manifestations include headache, irritability, poor concentration (Leere im Kopf), anxiety, delusions, hallucinations, stupor, apathy, psychomotor unrest, photophobia, tremor, ataxia, spastic paresis, fatigue, and depression.

Fatigue and insomnia progress to encephalopathy characterized by confusion, memory loss, and psychosis. Occasionally, frank disorientation, restlessness, and severe symptoms of the central nervous system occur. Peripheral neuritis and myelitis are occasionally encountered. As the disease advances, patients become disoriented, confused, and delirious. Eventually, patients become stuporous and comatose and they die.

Pellagra encephalopathy should be suspected in patients with alcohol intake presenting with rapidly progressive dementia combined with paraparesis or tetraparesis, neuropathy, visual disturbance, and myoclonus and may also be considered as a differential diagnosis of sporadic Creutzfeldt-Jakob disease.^[19]

Recurrences

Recurrent erythema usually is present on skin exposed to sunshine (ie, photosensitive eruption). Invariably, cheilitis, follicular hyperkeratosis on the face, pellagrous scrotal dermatitis, pellagrous vulvitis, porphyrinuria, funicular spinal syndrome, polyneuritis, and edema may be present. Atypical pellagra is oligosymptomatic or monosymptomatic. Abortive forms are termed pellagroids. Recurrences typically occur in the spring and summer.

Pellagra is the late stage of severe niacin deficiency. Primary pellagra results from inadequate nicotinic acid (ie, niacin) and/or tryptophan intake in the diet.

Secondary pellagra occurs when adequate quantities of niacin are present in the diet, but other diseases or conditions interfere with its absorption and/or processing.^{[20, 21, 22]} Such conditions include the following:

• Prolonged diarrhea
• Long-term alcoholism
• Chronic colitis, particularly colitis ulcerosa
• Ileitis terminalis
• Cirrhosis of the liver
• Tuberculosis of the GI tract
• Malignant carcinoid tumor
• Hartnup syndrome