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Image from Wikimedia Commons | Grook Da Oger.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

Malnutrition is defined by the World Health Organization (WHO) as a "cellular imbalance between the supply of nutrients and energy and the body's demand for them to ensure growth, maintenance, and specific functions."[1] Many diseases are directly or indirectly caused by a lack of essential nutrients in the diet.

Changes in the skin and mucosal membranes can offer valuable clues to the presence of nutritional deficiencies. For example, note the changes in the papillary mucosa of this patient, which take the form of scattered furrows and loss of filiform papillae.[2] The tongue and oral cavity are frequently the first regions of the body to show signs indicative of a vitamin deficiency. Tongue abnormalities may manifest as glossitis with atrophy of papillae, as well as ulcers and fissures, often accompanied by burning and tingling.

Image from Wikimedia Commons | James Heilman, MD.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

Skin pallor may indicate a nutrient deficiency, as in the pale hand of a woman with severe anemia (left) compared with the normal hand of her husband (right). Iron deficiency can range from depleted iron stores without functional or health impairment to iron deficiency with anemia, which affects the functioning of several organ systems.

Iron deficiency is a concern because it can delay normal motor or cognitive function in infants, increase the risk for underweight or preterm infants, and cause fatigue in adults that impairs their ability to do physical work. Iron deficiency may also affect memory and/or other mental functions in the pediatric population.[3]

Image from Medscape.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

Nail changes can be a clue in diagnosing some vitamin deficiencies. Koilonychia, or spoon nail (shown), can be associated with iron deficiency and protein deficiency (especially deficiency of sulfur-containing amino acids, such as cysteine or methionine).[4]

Beads that seem to drip down the nail like wax are associated with vitamin B deficiencies and some endocrine conditions (eg, diabetes mellitus, thyroid disorders, and Addison disease).

Brown-gray nails may be associated with vitamin B-12 (cobalamin) deficiency.

A central nail ridge may be caused by deficiencies in iron, folic acid, and/or protein.[4]

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

A 55-year-old man presents with the skin changes shown. He is taking isoniazid for tuberculosis of the gastrointestinal (GI) tract. He has also been experiencing GI disturbance for a few weeks, accompanied by irritability and sadness.

As signaled by the Casal necklace rash (shown), this patient has pellagra. Pellagra is often caused by a chronic lack of vitamin B-3 (niacin) in the diet, although it can also be a complication of isoniazid therapy and may occur despite vitamin B-6 (pyridoxine) supplementation.[5] People who obtain most of their food energy from maize (corn) are commonly affected.

The primary clinical manifestations of pellagra are the four Ds: photosensitive dermatitis, diarrhea, dementia, and death. Dermatologic features of this disorder include desquamation, erythema, scaling, and keratosis of sun-exposed areas.[5] The skin changes are never itchy. Oral nicotinamide or niacin typically reverses the clinical manifestations.[5]

Image from Medscape.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

A 64-year-old woman presents with a rash (shown) on both legs. She has a complex medical history (breast cancer, recurrent venous thrombosis, papillary thyroid cancer, anemia, leukopenia, splenomegaly, and bronchiectasis). The patient has not experienced pain, itching, or trauma and has had no contact with plants, new soaps, or lotions. She was receiving warfarin for several months, with a therapeutic international normalized ratio (INR) and a platelet count of 177,000/µL. The dietary history reveals that the patient was limiting her intake of fruits and vegetables.

Which of the following is the most likely diagnosis?

  1. Senile purpura
  2. Idiopathic thrombocytopenic purpura
  3. Vitamin C deficiency
  4. Excessive anticoagulation with warfarin
Image from Centers for Disease Control and Prevention (CDC).

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

Answer: C. Vitamin C deficiency.

Perifollicular hemorrhage (shown) is a clue to the presence of vitamin C (ascorbic acid) deficiency.[6] Insufficient vitamin C intake causes scurvy, an illness characterized by fatigue, widespread connective tissue weakness, and capillary fragility.[6,7]

Because it cannot be synthesized by the human body, vitamin C is an essential dietary component, with deficiencies avoided through consumption of fruits and vegetables or a diet fortified with ascorbic acid.[6,7]

Image courtesy of Desai VD, Hegde S, Bailoor DN, et al. Int J Clin Pediatr Dent. 2009 Sep;2(3):39-42. [Open access.] PMID: 25206121, PMCID: PMC4086578.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

The patient in the image presented with scorbutic gums attributable to vitamin C (ascorbic acid) deficiency. Oral changes associated with vitamin C deficiency include inflammation of the gums (gingivitis), as well as swollen, bleeding gums and loosening or loss of teeth—results of impaired collagen synthesis and subsequently weakened connective tissues.[6,7]

Vitamin C deficiency is rare in the United States, but people who ingest little or no vitamin C (ie, < 10 mg/day) for many weeks may get scurvy.[7]

Image from CDC.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

Scorbutic tongue is another oral change that can be identified in patients with scurvy. This child presented with inflammation of the tongue (glossitis) (shown), including areas of erythema and petechial submucosal hemorrhages.

The tongue may also be affected by nutritional deficiencies of vitamin B-12 (cobalamin), iron, folic acid, vitamin B-6 (pyridoxine), vitamin B-2 (riboflavin), vitamin B-3 (niacin), vitamin A, and zinc.

Image courtesy of Medscape | Forbes and Jackson.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

A 75-year-old woman presents with a lemon-yellow pallor and atrophic glossitis (smooth, shiny appearance of the tongue with loss of filiform papillae) (shown). She also has ataxia and weakness. She underwent a complete gastrectomy 2 years previously. Her hemoglobin level is 10 g/dL. Her peripheral blood smear is shown in the next slide.

Image from Medscape.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

The peripheral blood smear (shown) includes anisocytosis, macro-ovalocytes, and hypersegmented neutrophils, which are consistent with megaloblastic anemia. In the United States, megaloblastic anemia is most likely due to vitamin B-12 (cobalamin) deficiency (folic acid fortification has made folate-deficient megaloblastic anemia a very rare condition).[8-10]

It is crucial to recognize oral changes and other early signs of megaloblastic anemia so that replacement therapy can be initiated before irreversible neurologic effects occur. Macrocytosis precedes megaloblastic changes and is more common. Neurologic signs of megaloblastic anemia include posterior-column signs, followed by gait disturbances, vision problems, delirium, and dementia.[10,11] The presence of ataxia and weakness in this patient differentiates vitamin B-12 deficiency from folate deficiency.

Vitamin B-12 deficiency should be treated with B-12 injections.[10] Although high doses given orally yield results similar to those given via injection, patient adherence may be an issue.

Image from Medscape.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

A 2-year-old girl presents with persistent diarrhea and periorificial skin changes consisting of sharply demarcated, brightly erythematous plaques (shown). Her mother also notes that the child's hair is falling out. The child was successfully weaned from breast milk at age 5 months. Her older sibling had the same condition at age 3 years.

This child has primary acrodermatitis enteropathica, an autosomal recessive metabolic disorder causing zinc deficiency and characterized by periorificial and acral dermatitis, alopecia, and diarrhea.[12] In this disorder, breast milk usually provides sufficient bioavailable zinc in infants until about age 4-6 months, after which complementary foods are required to provide additional zinc.[13] Measuring the zinc level in breast milk can differentiate between primary and acquired deficiencies. Reduced serum alkaline phosphatase levels may indicate zinc deficiency in the presence of a normal serum zinc level.[12]

Hypozincemia in adults is usually caused by a dietary deficiency.[13] Other common causes include malabsorption, bariatric surgery, diarrhea, chronic liver/renal disease, sickle cell disease, diabetes, and cancer.[13]

Image from Wikimedia Commons | Matthew Ferguson 57.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

Angular cheilitis (cheilosis or angular stomatitis) is an inflammatory lesion at the corner of the mouth (shown). In severe cases, cracks or splits may form and bleed. Common causes of cheilitis include vitamin B-2 (riboflavin) deficiency,[14] iron deficiency anemia, anorexia nervosa or bulimia, Plummer-Vinson syndrome, weather (chapped lips), infections (commonly fungal), and medications that dry the skin (eg, isotretinoin).[15]

Vitamin B-2 deficiency is rare in the United States, owing to dietary fortification of many foods[16]; when it arises, it is usually in the presence of other vitamin B deficiencies.[14] It is typically managed with oral intake of vitamin B-2. Common sources of this vitamin in Western diets include oats and breakfast cereals, yogurt, milk, clams, mushrooms, almonds, and eggs.[14,16]

Image from Datta AK, Ghosh T, Nayak K, Ghosh M. Cases J. 2008;1(1):158. [Open access.] PMID: 18801184, PMCID: PMC2559824.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

Copper deficiency, though rare, can arise in combination with other nutritional deficiencies and can be seen in patients with a history of remote gastric bypass surgery or a malabsorptive disorder.[17] Clinical features of copper deficiency include fragile, abnormally formed hair; skin depigmentation; anemia; myeloneuropathy; hepatosplenomegaly; and osteoporosis.[17-21] Neurologic manifestations may mimic those of vitamin B-12 (cobalamin) deficiency.

Menkes kinky hair disease (as seen in the infant above) is a rare X-linked recessive disorder that occurs when the transport protein mediating copper uptake from the intestine mutates; it results in severe copper deficiency that manifests early in infancy.[21]

Image from Wikimedia Commons | Foiltape.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

A young child presents to the pediatrician with yellowish discoloration of the skin. The discoloration is more visible on the nose under artificial light (shown) and on the palms of the hands but spares the sclera and mucous membranes.

Which of the following conditions is known to cause the above clinical picture?

  1. Hypothyroidism
  2. Ingestion of large amounts of carrots
  3. Diabetes mellitus
  4. Liver disease
  5. All of the above
Images from Wikimedia Commons | Norge0209.

Cutaneous and Mucosal Clues to Nutritional Deficiencies

Mose July, MD; George M Yousef, MD; Lynne Goebel, MD | May 24, 2021 | Contributor Information

Answer: E. All of the above.

Carotenemia (left) and carotenoderma result from deposition of beta carotene, a provitamin A from plant sources, in the fat-soluble stratum corneum.[22] The yellowish discoloration of the skin is first observed on the nose, nasolabial folds, palms of the hands, soles of the feet, and then, eventually, the entire body; however, the sclera and mucous membranes are spared, distinguishing this condition from jaundice.[22]

Carotenemia is particularly common among infants and toddlers who eat large amounts of puréed vegetables (particularly carrots and sweet potatoes).[22] Other, less common causes include diabetes mellitus, hypothyroidism, anorexia nervosa, and hepatorenal diseases, due to the decreased conversion of beta carotene to retinol.

Carotenemia is a benign condition, and elimination of carotene-rich foods results in the gradual disappearance of the yellowish discoloration (right).[22] Provitamin A is not highly regulated and is very unlikely to cause vitamin A toxicity.

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