Brote por Dieta Keto.

Prurigo pigmentosa as the "keto rash": I'm a believer

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By Warren R. Heymann, MD
February 5, 2020
Vol. 2, No. 5

Patients are attuned to their diets — healthy, unhealthy, or trendy. Unquestionably, certain foods exacerbate specific dermatoses — just ask any dermatitis herpetiformis patient how they fare with a slice of Sicilian pizza. More often the situation is nebulous. When patients ask me random questions, "Do you think kumquats are aggravating my eczema?" my usual response is not to be dismissive, shrug my shoulders, and say "I don't know — let's look it up in PubMed for real references, not Google." (There are references noting that kumquats, as citrus fruits, may aggravate atopic dermatitis by non-IgE mechanisms.) (1)

As stated on the website Healthline: "If you've been involved in the health and wellness world lately, you've likely heard of the keto diet. The ketogenic diet, also referred to as the keto diet, is a low-carb, high-fat diet. With a very low carbohydrate intake, the body can run on ketones from fat instead of glucose from carbs. This leads to increased fat-burning and weight loss. However, as with any drastic dietary change, there can be some unwanted side effects. Initial side effects of the keto diet may include brain fog, fatigue, electrolyte imbalance, and even a keto rash." (2)

The "keto rash" is prurigo pigmentosa (PP), an uncommon dermatosis consisting of a network of erythematous, pruritic papules evolving into reticulated hyperpigmentation with a specific predilection for the trunk. It is seen mostly in young adults, more often in women. Originally described in Japan, there have been an increasing number of reports worldwide. PP progresses through several stages of development, commencing as erythematous macules which evolve to urticarial papules and papulovesicles. Subsequently, the lesions become crusted or scaly. A few weeks later, they spontaneously resolve, leaving behind reticulated pigmentation. The histologic features vary with each stage of lesional morphology (initially a neutrophilic infiltrate, with spongiosis, vacuolar alteration, and late dermal melanophages). Therapy is with tetracycline antibiotics (minocycline, doxycycline) or dapsone. Topical steroids may help pruritus but have little effect on the rash itself. Recurrences of PP may occur.

Image courtesy of Warren R. Heymann, MD

The cause of PP is unknown. Several triggering factors have been considered: friction from clothing, allergic contact dermatitis, sunlight, and nutritional factors, including dieting, diabetes, and ketonuria. The histologic presence of follicular bacterial colonies supports the theory that prurigo pigmentosa may be a reactive inflammatory response to bacterial folliculitis. Previously, the benefit of treating PP with antibiotics was attributed to the anti-inflammatory effects of the drugs; while that may be true, perhaps in PP, it is really their antibacterial effect that is responsible for the improvement. (3)

Recently, a graduating resident physician of Asian descent presented with an undiagnosed rash on her back of a few months' duration. It was initially red and pruritic. Topical steroids offered little relief. The diagnosis — PP — was immediately apparent. Before I even discussed the nature of PP, she inquired: "I'm trying to take off some weight before my new job. This rash appeared within a few weeks of starting a ketogenic diet. Do you think that had something to with it?"

As Popeye would say — "Well, blow me down!"

PP was initially described in 1971 by Nagashima et al (4); as of the 1990s, ample literature appeared noting the correlation of diabetes, ketosis, and PP, with improvement of the rash with insulin. (5,6) Teraki et al detailed 10 patients with PP. Five were on a diet to lose weight, two patients had a loss of appetite from stress, and in one patient insulin dependent diabetes mellitus developed at the same time as the skin lesions. Ketosis was observed in 8 of the 10 patients. The eruption cleared when the ketosis diminished. (7) Recently, a 17-year-old boy with PP was described, not having ingested carbohydrates for a year. Within a week of adjusting his diet and administering doxycycline, his PP improved dramatically. (8) PP may also accompany bariatric surgery, presumably due to ketosis (9,10)

How ketosis is pathogenic in PP remains to be defined. According to Hartman et al, increased ketone bodies upregulate intercellular adhesion molecule 1 (ICAM-1) and leukocyte function-associated antigen 1 (LFA-1), a phenomenon also seen in lesional keratinocytes of PP, thereby linking ketosis with inflammation. (11) Perhaps this microenvironment alters the microbiome, allowing for growth of the newly recognized intrafollicular bacteria.

I am dedicating this commentary to two icons of my youth who recently passed away — Arte Johnson (of Rowan and Martin's Laugh-In) and Peter Tork (of the Monkees). I find the concept of ketosis and PP verrrry interesting and now I'm a believer. When patients present with PP, dermatologists should inquire about diabetes mellitus, specific dietary changes, and recent bariatric surgery. If patients are at risk for ketosis, dietary carbohydrate supplementation may be all that is needed to alleviate this very interesting eruption.

Point to Remember: There is ample literature to support the association of ketosis (and a ketogenic diet) to prurigo pigmentosa. Correcting the ketotic state is therapeutic.

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Our Expert's Viewpoint

Harper Price, MD
Division Chief, Pediatric Dermatology
Phoenix Children's Hospital

It is unusual that a day won't go by in our clinics without a patient or their family member asking about the relationship between foods and the skin — whether it be for overall skin health (should I take a hair and nail vitamin?) or specific skin eruptions (e.g., the dreaded — is the dairy causing my eczema or acne?). Although many times the evidence is little to none at best to support our patient's hunches about what might be causing their skin rashes, this is not so in the case of PP. Dietary questioning, especially regarding carbohydrate intake and exclusion, becomes the key to the diagnosis in PP. This is well-supported by the current literature, despite the fact that the role of a ketotic state in the pathogenesis of PP remains to be elucidated. Along with the classic clinical presentation of PP and appropriate patient history, we can reassure our patient of the diagnosis and offer (oftentimes) a non-pharmaceutical treatment plan, especially important in the era of great emphasis on proper antibiotic stewardship and avoidance of polypharmacy.

1. Brockow K, Hautmann C, Fötisch K, Rakoski J, et al. Orange-induced skin lesions in patients with atopic eczema: Evidence for a non-IgE-mediated mechanism. Acta Derm Venereol 2003; 83: 44-8.

2. Keto rash: What it is, why it happens, and how to cure it. Healthline, April 30, 2019. https://www.healthline.com/health/keto-rash

3. Heymann WR. Getting within a hair's breadth of understanding prurigo pigmentosa. Dermatology Insights and Inquiries. March 2, 2017.

4. Nagashima M. Prurigo pigmentosa – clinical observations of our 14 cases. J Dermatol 1978; 5: 61-7.

5. Murao K, Urano Y, Uchida N, Arase S. Prurigo pigmentosa associated with ketosis. Br J Dermatol 1006; 134: 379-381.

6. Yokozeki M, Watanbe J, Hotsubo T, Matsumura T. Prurigo pigmentosa disappeared following improvement of diabetic ketosis by insulin. J Dermatol 2003; 30: 257-8.

7. Teraki Y, Teraki E, Kawashima M, Nagashima M, Shiohara T. Ketosis is involved in the origin of prurigo pigmentosa. J Am Acad Dermatol 1996; 34: 509-511.

8. Michaels JD, Hoss, DiCaudo DJ, Price H. Prurigo pigmentosa after a strict ketogenic diet. Pediatr Dermatol 2015 32: 248-251.

9. Al-Dawsari NA, Al-Essa A, Shahab R, Raslan W. Prurigo pigmentosa following laparoscopic gastric sleave. Dermatol Online J 2019; May 15; 25 (5).

10. Alshaya MA, Turkmani MG, Alissa AM. Prurigo pigmentosa following ketogenic diet and bariatric surgery: A growing association. JAAD Case Rep 2019; 5: 504-507.

11. Hartman M, Fuller B, Heaphy MR. Prurigo pigmentosa induced by ketosis: Resolution through dietary modification. Cutis 2019; 103: e10-e13.



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