Cutaneous Signs of Malnutrition Secondary to Eating Disorders

It is possible that anemia and dehydration can worsen acrocyanosis due to impaired delivery of oxyhemoglobin to the body’s periphery.⁶³ In a study of 14 ED patients requiring inpatient care, 6 were found to have underlying anemia following intravenous fluid supplementation.⁶⁴ On admission, the mean (SD) hemoglobin and hematocrit across 14 patients was 12.74 (2.19) and 37.42 (5.99), respectively. Following intravenous fluid supplementation, the mean (SD) hemoglobin and hematocrit decreased to 9.88 (1.79)(P<.001) and 29.56 (4.91)(P=.008), respectively. Most cases reported intentional restriction of dietary sodium and fluid intake, with 2 patients reporting a history of diuretic misuse.⁶⁴ These findings demonstrate that hemoglobin and hematocrit may be falsely normal in patients with AN due to hemoconcentration, suggesting that anemia may be underdiagnosed in inpatients with AN.

Beyond treatment of the underlying ED, acrocyanosis therapy is focused on improvement of circulation and avoidance of exacerbating factors. Pharmacologic intervention rarely is needed. Patients should be reassured that acrocyanosis is a benign condition and often can be improved by dressing warmly and avoiding exposure to cold. Severe cases may warrant trial treatment with nicotinic acid derivatives, α-adrenergic blockade, and topical minoxidil, which have demonstrated limited benefit in treating primary idiopathic acrocyanosis.⁶³

Carotenoderma

Carotenoderma—the presence of a yellow discoloration to skin secondary to hypercarotenemia—has been described in patients with EDs since the 1960s.^65,66 Beyond its clinical appearance, carotenoderma is asymptomatic. Carotenoids are lipid-soluble compounds present in the diet that are metabolized by the intestinal mucosa and liver to the primary conversion product, retinaldehyde, which is further converted to retinol, retinyl esters, and other retinoid metabolites.^67,68 Retinol is bound by lipoproteins and transported in the plasma, then deposited in peripheral tissues,⁶⁹ including in intercellular lipids in the stratum corneum, resulting in an orange hue that is most apparent in sites of increased skin thickness and sweating (eg, palms, soles, nasolabial folds).⁷⁰ In an observational study of ED patients, Glorio et al¹⁴ found that carotenoderma was present in 23.77% (29/122) and 25% (4/16) of patients with BN and other specified feeding or eating disorder, respectively; it was not noted among patients with AN. Prior case reports have provided anecdotal evidence of carotenoderma in AN patients.^66,71 In the setting of an ED, increased serum carotenoids likely are due to increased ingestion of carotene-rich foods, leading to increased levels of carotenoid-bound lipoproteins in the serum.⁷⁰ Resolution of xanthoderma requires restriction of carotenoid intake and may take 2 to 3 months to be clinically apparent. The lipophilic nature of carotenoids allows storage in body fat, prolonging resolution.⁷¹

Hair Changes

Telogen effluvium (TE) and hair pigmentary changes are clinical findings that have been reported in association with EDs.^14,16,19,72 Telogen effluvium occurs when physiologic stress causes a large portion of hairs in the anagen phase of growth to prematurely shift into the catagen then telogen phase. Approximately 2 to 3 months following the initial insult, there is clinically apparent excessive hair shedding compared to baseline.⁷³ Studies have demonstrated that patients with EDs commonly have psychiatric comorbidities such as mood and anxiety disorders, obsessive compulsive disorder, posttraumatic stress disorder, and panic disorder compared to the general population.^6,74-76 As such, stress experienced by ED patients may contribute to TE. Despite TE being commonly reported in ED patients,^16-18 there is a lack of controlled studies of TE in human subjects with ED. An animal model for TE demonstrated that stressed mice exhibited further progression in the hair cycle compared with nonstressed mice (P<.01); the majority of hair follicles in stressed mice were in the catagen phase, while the majority of hair follicles in nonstressed mice were in the anagen phase.⁷⁷ Stressed mice demonstrated an increased number of major histocompatibility complex class II⁺ cell clusters, composed mostly of activated macrophages, per 12.5-mm epidermal length compared to nonstressed mice (mean [SEM], 7.0 [1.1] vs 2.0 [0.3][P<.05]). This study illustrated that stress can lead to inflammatory cell recruitment and activation in the hair follicle microenvironment with growth-inhibitory effects.⁷⁷

The flag sign, or alternating bands of lesser and greater pigmentation in the hair, has been reported in cases of severe PEM.³¹ In addition, PEM may lead to scalp alopecia, dry and brittle hair, and/or hypopigmentation with periods of inadequate nutrition.^29,78 Scalp hair hypopigmentation, brittleness, and alopecia have been reported in pediatric patients with highly selective eating and/or ARFID.^79,80 Maruo et al⁸⁰ described a 3-year-old boy with ASD who consumed only potato chips for more than a year. Physical examination revealed reduced skin turgor overall and sparse red-brown hair on the scalp; laboratory testing showed deficiencies of protein, vitamin A, vitamin D, copper, and zinc. The patient was admitted for nutritional rehabilitation via nasogastric tube feeding, leading to resolution of laboratory abnormalities and growth of thicker black scalp hair over the course of several months.⁸⁰

Neuroendocrine control of keratin expression by thyroid-stimulating hormone (TSH) and thyroid hormones likely plays a role in the regulation of hair follicle activities, including hair growth, structure, and stem cell differentiation.^81,82 Altered thyroid hormone activity, which commonly is seen in patients with EDs,^24,25 may contribute to impaired hair growth and pigmentation.^26,51,83-85 Using tissue cultures of human anagen hair follicles, van Beek et al⁸⁵ provided in vitro evidence that T₃ and T₄ modulate scalp hair follicle growth and pigmentation. Both T₃- and T₄-treated tissue exhibited increased numbers of anagen and decreased numbers of catagen hair follicles in organ cultures compared with control (P<.01); on quantitative Fontana-Masson histochemistry, T₃ and T₄ significantly stimulated hair follicle melanin synthesis compared with control (P<.001 and P<.01, respectively).⁸⁵ Molecular studies by Bodó et al⁸³ have shown that the human scalp epidermis expresses TSH at the messenger RNA and protein levels. Both studies showed that intraepidermal TSH expression is downregulated by thyroid hormones.^83,85 Further studies are needed to examine the impact of malnutrition on local thyroid hormone signaling and action at the level of the dermis, epidermis, and hair follicle.

Discovery of TE, hair loss, and/or hair hypopigmentation should prompt close investigation for other signs of thyroid dysfunction, specifically secondary to malnutrition. Imbalances in TSH, T₃, and T₄ should be corrected. Nutritional deficiencies and dietary habits should be addressed through careful nutritional rehabilitation and targeted ED treatment.