Episode 42 – A Solely Acral Rash

Why are some rashes acral?

For this episode, Hannah, Avi, and Tony were joined by Dr. Steven Chen (@Dr.StevenTChen), a dermatologist and internist at Massachusetts General Hospital. Steven brought along a fascinating question: why are some rashes acral?

In order to answer the question, one must first recall that an “acral” rash is one found on the distal body parts. This includes the whole hand, the whole foot, and also the ears. And while many have an immediate association between these locations and the rash of secondary syphilis¹, many conditions present with this distribution. Other examples include Rocky Mountain Spotted Fever, Hand-Foot-Mouth Disease, erythema multiforme (EM), and Stevens-Johnson syndrome (SJS)².

With this background, we can explore why certain conditions present in an acral distribution. The simplest approach is to consider how acral skin is different than the rest of the body. One potentially relevant difference is that the temperature at acral sites might be slightly lower than the core temperature. This difference helps explain eruptions such as perniosis and Raynaud’s.

Another difference is texture. Palmar skin has relatively less subcutis, but thicker epidermis that’s really compact. And it is certainly true that people generally do not grow hair on their palms and soles. These areas are known as glabrous skin and are smooth and without hair follicles. One final difference is an over-representation of eccrine glands on the palms and soles. These are the major sweat glands and are more tightly concentrated here than on other surfaces, like the abdomen.

A great example of how these differences lead to an acral rash can be found with something called Hand-foot syndrome. This is an eruption centered on the palms and soles that occurs with certain chemotherapeutic agents, particularly cytarabine. It presents with very red palms and soles with each cytarabine dose. The reason: cytarabine is excreted in the eccrine glands, so the higher concentration of eccrine glands in the palms and soles lends them to being affected preferentially!

This knowledge leads directly to treatment. If the goal is to decrease the excretion of cytarabine into the palms and soles, the solution should cause vasoconstriction and a resulting decrease in delivery of the drug to the palms. The easiest way to do this: have the patient hold icepacks during their infusions.

Another example is acute cutaneous graft versus host disease (GVHD). This condition is difficult to differentiate from a usual morbilliform drug eruption, but one of the giveaways is how it starts. GVHD tends to start acrally, specifically on the palms and soles. Unlike a drug eruption that starts on the torso and spreads outwards, GVHD starts distally and moves inward. What explains this? The classic finding on pathology is involvement of the inflammatory infiltrate in the eccrine gland.

Returning to temperature, this may play a role in some acral rashes. There is evidence demonstrating that Treponema pallidum replicates best between 33 and 35 degrees Celcius. This could explain why the acral surfaces are often involved, but the same doesn’t hold true for other spirochetes. For example, Borrelia also replicates better at those temperatures but we don’t often see disseminated Lyme disease on acral surfaces.

Some viruses (e.g., parvovirus B19) cause a purpuric gloves and socks syndrome and an acrally distributed purpuric eruption. And there is support for the idea that some strains of porcine parvovirus preferentially replicate at different temperatures though as with syphilis, the connection is far from settled.

Take Home Points

1. Acral rashes involve distal extremities, the entire hand/foot, or even the ears.
2. Acral distribution may help differentiate rashes with similar morphologies, such as GVHD vs. morbilliform drug eruptions. 
3. Understanding microscopic anatomical differences can help inform treatment recommendations, such as ice packs to prevent cytarabine hand-foot syndrome

CME/MOC

Click here to obtain AMA PRA Category 1 Credits™ (1.00 hours), Non-Physician Attendance (1.00 hours), or ABIM MOC Part 2 (1.00 hours).

Listen to the episode

https://oembed.libsyn.com/embed?item_id=22020686

Credits & Citation

◾️Episode written by Steven Chen
◾️Show notes written by Tony Breu and Steven Chen
◾️Audio edited by Clair Morgan of nodderly.com

Chen, ST, Cooper AZ, Abrams HR, Breu AC. A Solely Acral Rash. The Curious Clinicians Podcast. February 2, 2022

---

Image credit: https://www.cmaj.ca/content/176/1/33

1. And even the rash of secondary syphilis is more than just acral. It initially presents on the flanks and shoulders as a papulosquamous non-pruritic eruption, and then appears later on a variety of places, such as the moth-eaten alopecia on the scalp, the split pea papules by the oral commissures, the “necklace of venus,” which are hypopigmented macules mainly on the neck, and the palms and soles where you see similar papules to the torso. We usually call them “copper pennies,” because of their appearance.
2. Another good example is EM/SJS. The lesions are everywhere on the body, but the acral sites are involved more frequently than in other eruptions.