This article was prepared by Jelaun K. Newsome, D.O., Michelle S. Newsome, Ph.D., and Joseph J. Pavelites, M.D.
You are a supervising military flight surgeon working in a military aviation clinic. It is the end of the day, and you are headed to the hangar to check in on one of your workers. You meet up with one of your junior flight surgeons who has just come back from missing the last few days of work. You offer him a seat, but he states that it is “too painful to sit” and he would rather stand while you talk. You notice that he appears slightly uncomfortable and he is using his hand to hold his uniform shirt from contacting his abdomen. After finishing work-related business, you politely inquire about his pain.
He describes that a week ago he had a tooth extracted. The oral surgeon was preparing his mandible for a dental implant, and he was prescribed prophylactic amoxicillin as part of the procedure. The day after the extraction, he noticed that his skin started to feel like it was stinging as if he had “sunburn all over his body.” Your junior reports that the skin pain grew so bad to the touch that he could not brush his hair, wear gloves, or use covers when he slept. Although he stopped the amoxicillin after two doses, the painful burning sensation increased from 3/10 to 7/10. The service member also called his oral surgeon, who was not sure of the cause of the problem and recommended that he proceed to the emergency department. The flight surgeon hands you a copy of the discharge summary from the civilian emergency department.
At the emergency department, the service member had labs drawn and a physical exam. Prior medical and surgical history notes the previous oral surgery, no known drug allergies, and the current use of a medium-strength topical steroid and calcipotriene. The results of a complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, and urinalysis were within normal limits. The physical exam of this 31-yr-old Caucasian man revealed no signs of anaphylaxis. Furthermore, the skin exam showed only a few pre-existing scaly plaques on the knees and elbows and some minor acne on the upper back. The attending physician noted that, by using the tuft of a cotton swab, “all dermatomes tested” generated an 8/10 pain to light touch. He was placed on a 6-d course of oral steroids and sent home. The flight surgeon states that most of his skin feels much better, but he still has 5/10 pain to light touch on his abdomen.
1. What is topical calcipotriene and what is it most likely being used for in this patient’s case?
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Vitamin A analog used for the treatment of cystic acne.
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Ergosterol inhibitor used for the treatment of a fungal infection.
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Inhibition of histone acetyltransferase and recruitment of histone deacetylases activity for treatment of inflammation.
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Vitamin D analog used for the treatment of psoriasis.
ANSWER/DISCUSSION
1. D. Calcipotriene (calcipotriol) is a synthetic drug derived from calcitriol, a form of vitamin D3. 1 Calcipotriene works by regulating the production and growth of skin cells and is used mainly for the treatment of psoriasis. However, this drug has many off-label applications that are alternative therapies for many other dermatological diseases, such as actinic keratoses, seborrheic keratoses, and lichen planus, among others. 1 Answer A describes the mechanism of action of retinoids. One first line agent for acne would include topical retinoids, while more severe acne would include consideration of oral isotretinoin, among other therapies. 2 Answer B is the mechanism of action of azole drugs, which inhibit the biosynthetic pathway that produces ergosterol, a sterol that resides in the cell membrane of fungi and maintains membrane integrity. This antifungal class of medications includes fluconazole, itraconazole, and miconazole. 3 The inhibition of histone acetyltransferase and recruitment of histone deacetylases activity for the treatment of inflammation is incorrect because this is the mechanism of inhaled corticosteroids in decreasing the inflammation seen in asthma, chronic obstructive pulmonary disease, and other common lung diseases. 4
Talking with this physician, who is assigned as part of a flight crew, you get concerned that he may have a condition that is disqualifying for flight. Not only is the out-of-proportion pain (allodynia) concerning, but the medications he has been using raise an eyebrow. Knowing that calcipotriene is often used for many skin disorders, you ask the service member what condition(s) he is being treated for.
2. Which of the following does not accurately describe the stated condition?
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Porokeratosis: small, scaly plaques of the skin, often brownish in color, with a ridge-like border that can appear anywhere on the skin, including the mouth and genitals.
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Psoriasis: a chronic, noncontagious, autoimmune disease of the skin with plaques that can be red, pink, purple, dry, pruritic, and scaly.
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Lichen planus: an autoimmune disease characterized by an area of inflammation and fibrosis (thickening and hardening) of the skin due to increased collagen.
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Pityriasis rubra pilaris (PRP): a group of rare skin disorders that present with reddish-orange colored scaling plaques with well-defined borders that may cover the entire body or just parts such as the elbows and knees, palms and soles.
ANSWER/DISCUSSION
2. C. This is the correct answer as it better describes morphea (or localized scleroderma). Lichen planus is an idiopathic condition characterized by papules and polygonal plaques that are shiny, flat-topped, and firm on palpation (Boch). They are often crossed by fine white lines called Wickham striae. 5 Porokeratosis is a rare disorder that generally impacts adults but can develop in childhood. It can be found anywhere on the body and, in addition to the above description, presents as keratotic papules. 6 Psoriasis is a chronic inflammatory disease that affects the skin with scaly patches or plaques. 7 It can be triggered by factors such as genetics, environment, or a combination of both. 8 Lastly, PRP is an inflammatory papulosquamous disorder. 9 It can present as different variants (Types I–V) and can greatly impact quality of life. Type I PRP (the most common variant) presents itself as erythematous papules that emerge in a follicular pattern. 10 Of note, calcipotriene has been used to treat all the above stated conditions.
The service member states that he has been treated for mild to moderate psoriasis for the last 2 yr. He states that it is well controlled on his current medication regimen. However, as you probe further, he reveals that he has never had an aviation medicine workup to ascertain a need for a waiver to continue as a member of a flight crew. After you admonish him for not doing his due diligence, you give him some homework. By the next day, you expect a summary from him concerning the aeromedical policies and procedures of the various U.S. military branches and relevant civilian flight organizations for his condition.
3. Which one of the following is false about psoriasis and its possible impact on flight safety?
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Psoriasis is generally easily treated and has little potential to impact safety of flight.
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Complications of psoriasis can include systemic medical diseases such as psoriatic arthritis.
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Treatment of psoriasis is often not benign and can negatively affect multiple organ systems.
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Skin manifestations of psoriasis can lead to a lack of compliance with the wearing and proper use of safety equipment such as seat harnesses and helmets.
ANSWER/DISCUSSION
3. A. Psoriasis is an inflammatory skin and systemic disorder triggered by a complex mix of genetic, environmental, and infectious factors. Skin and systemic manifestations can greatly impact the safety of flight. Scalp involvement is possible and may interfere with helmet use. Palmar and plantar involvement may interfere with the use of flight controls. Pruritus or pain can be distracting to flight. Symptoms may also interfere with proper crew rest, and complications such as psoriatic arthritis can also cause distracting pain. 11 In adults with psoriasis, 90% have plaque psoriasis and up to 30% of those adults develop psoriatic arthritis. Psoriasis has been found to be an independent risk factor for various comorbidities such as cardiovascular disease, diabetes mellitus, and inflammatory bowel disease. 12 Treatments range from topical corticosteroids, vitamin D analogs, and tazarotene to systemic treatments of nonbiological and biological agents and ultraviolet B phototherapy. 12 Each medication class carries its own risks of known side effects and possible adverse effects. Repeated rubbing or trauma to the skin can cause interference with the wear of protective aviation equipment and distraction by pruritus or pain.
As you wait for your junior to summarize the aeromedical policies and procedures, you decide to investigate the possible causes of his pain. You suspect that the amoxicillin was not likely to have caused an allergic reaction, but you are not sure of its role in the allodynia and the flare-up of psoriasis. Looking in the literature you discover that amoxicillin can cause psoriasis to worsen. Other antibiotics such as tetracyclines have also been implicated in psoriasis flares. 13 In addition, it is reported that nearly 90% of those with psoriasis suffer symptoms that include pruritus, discomfort, and hyperalgesia. Pruritus is the most common symptom of psoriasis. However, a little less than half of patients experience pain in the lesion area, accompanied by a decreased pressure pain threshold, especially in the scalp and palm areas. There has also been a reported tendency for the pressure and pain thresholds to be decreased in the non-lesion areas of patients with psoriasis. Chronic inflammation in people with psoriasis can also lead to the release of prostaglandin E2 and prostaglandin I2, which stimulate pain receptors and lead to neuropathic pain. In addition, it appears that nociceptive neurons can fail to consistently transmit sensory signals in lesion areas, as well as non-lesion areas, a concern for safety in flight. 14
4. Which of the following could be seen in psoriasis?
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Excessive innervation in psoriatic lesions.
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Increased levels of intralesional nerve growth factor.
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Increased content of neuropeptides in the plasma.
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Hyperalgesia psoriatic skin expresses higher levels of inflammatory substances [interleukin (IL) 33, IL-17, IL-31, and IL-33, specifically].
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All of the above.
ANSWER/DISCUSSION
4. E. Numerous studies have shown that nerve innervation in psoriatic lesions is higher than in non-psoriatic skin, including “the total number of nerve fibers, density, total length, and the proportion of nerve fiber penetration into the epidermis.” 14 Research has demonstrated the elevation in the expression of nerve growth factor and neuropeptides in psoriatic tissue vs. non-psoriatic tissue. Furthermore, pruritic and hyperalgesic psoriatic skin contains elevated levels of various interleukins found to be significant inflammatory factors in the pathogenesis of psoriasis and dysfunction in sensory nerves. Targeting these inflammatory factors with biological medications has been shown to improve pruritis and pain. 14
The service member sends you the summary that you assigned. He dutifully reviewed the aeromedical policies concerning psoriasis from the International Civil Aviation Organization (ICAO), Federal Aviation Administration (FAA), Army, Navy, and Air Force. Upon reviewing the literature, ICAO is the only organization that does not specifically mention psoriasis. However, while not discussing psoriasis or psoriatic arthritis, ICAO recommends consideration of the effects of long-term treatment of arthritis in general regarding possible interference in flight safety or cause of sudden incapacitation. 15
The FAA combines guidance concerning psoriasis with that of arthritis. In this case a special issuance is required. According to the Guide for Aviation Medical Examiners, an FAA aviation medical examiner (AME) must defer for FAA decision. Following initial approval for a special issuance, AMEs may then reissue an airman medical certificate via an AME Assisted Special Issuance. At each reissuance, the applicant must provide an authorization granted by the FAA, the type of psoriasis, a general assessment of the condition and its effect on daily activities, and the name and dosage of medication(s) used for treatment and/or prevention with comment regarding side effects. 16
The U.S. Army considers any history of psoriasis disqualifying. Waivers are considered on an individual basis. Mild localized cases that are controlled with topical medications and do not affect the aircrew member’s ability to operate safely are readily waivered. Dermatology consultation is required. 17
According to the U.S. Navy Aeromedical Reference and Waiver Guide’s section on psoriasis, “A history of psoriasis is disqualifying for entry into aviation.” Like the U.S. Army, a waiver may be considered for mild cases, such as those only needing topical steroids. Waiver is not recommended for more severe cases. Dermatology consultation discussing treatment recommendations and response to therapy is also required. 18
The U.S. Air Force states that the diagnosis of psoriasis is disqualifying for flying class I/IA, II, III, and special warfare airmen. Consideration of waiver is possible and must include a thorough history (including impact on aviation equipment use and current therapy), physical, and dermatology consult. If there is psoriatic arthritis, pertinent radiographs, disease- and medication-specific laboratory tests, and a rheumatology consult are also required. 11
Commensurate with the flight surgeon’s branch of military service, he is required to be worked up for a waiver for psoriasis. In turn, the medications that he is using do not require a waiver in themselves. While his pain recedes, his aeromedical provider temporarily restricts him from flight duties and begins the necessary tests and referrals for a waiver application. A full workup reveals that he does not have psoriatic arthritis, inflammatory bowel disease, or other complications. Dermatology confirms that he is on the appropriate and effective medication regimen but cautions against the use of certain antibiotics to help prevent exacerbation of his condition.
A waiver is granted to the service member with the provision that he must be examined by a dermatologist yearly and that waiver continuance will be reviewed if his allodynia returns or the disease advances with further complications. Your colleague is returned to full flight status knowing that he is a little bit wiser about his condition as well as the proper application of aeromedical policies and procedures.
Newsome JK, Newsome MS, Pavelites JJ. Aerospace medicine clinic: psoriasis, allodynia, and hyperalgesia. Aerosp Med Hum Perform. 2024; 95(9):722–725.