Carolinas Research Day 2021

Phototoxic Dermatits Cary Pellizzeri, OMS3 1 & Lindsey Tijiattas-Saleski, DO, MBA, FACOEP 2 1 Edward Via College of Osteopathic Medicine – Carolinas Campus 2 PRISMA Health/Edward Via College of Osteopathic Medicine – Carolinas Campus

Abstract

Results

Differential Diagnosis Continued:

Phototoxic reactions to sunlight can be attributed to many different exogenous agents. Topical creams, plants, and systemic medications all contribute to increasing photosensitivity. Among them, doxycycline is one of the most common causes of phototoxic reactions in conjunction with exposure to UV light.(5) We have found that the primary treatment for exogenous photodermatitis is to stop the offending agent and educate the patient on limiting UV exposure during treatment. (4,7)

Patient A: 48 yo female presents to the emergency department with a rash. She had been started on doxycycline the day prior for sinusitis. After being exposed to the sun while working in her yard, she noticed an erythematous, pruritic painful rash on the sun exposed areas of her face and arms. The severity was described to be worse than a typical sun burn. She presented to the ED with concerns that this was an allergic reaction. She had stable vital signs and no other systemic symptoms. Denied fevers, chills, rash on palms or soles, rash or lesions on mucus membranes, gastrointestinal symptoms, or previous episodes of similar symptoms.

- Pellagra is chronic niacin deficiency which presents with dermatitis, diarrhea, dementia, and death. Niacin deficiency depletes nicotinamide adenine dinucleotide (NAD), a substrate in the UV-induced DNA repair pathway. 2,8 This presents as erythema in sun-exposed areas that progresses to hyperpigmentation and scaling. A characteristic feature of the disease is Casal's necklace, which is a ring of erythema and hyperpigmentation extending around the neck onto the chest. - Systemic Lupus Erythematosus can cause photosensitization both in autoimmune and drug-induced forms. The classic butterfly rash of SLE appears after exposure to sunlight and can be mistaken for phototoxicity. It is important to assess ANA, ENA, and histone antibodies to determine the cause. 2,4

Introduction

Exogenous photosensitivity is cutaneous sensitivity to UVR induced by external substances. Drug-induced photosensitivity commonly occurs in clinical practice, representing up to 8% of reported cutaneous adverse events from drugs. 6 Photosensitive reactions to UV are split between phototoxicity and photoallergy. Phototoxic reactions occur within 24 hours of exposure to relatively intense sunshine. 1 Common presentations include sunburn-like sensations, including burning and erythema, on sun-exposed areas like the nose, upper cheeks, lips, neck, and chest, and dorsal aspects of the forearms, hands, and fingers (Figure 1). 1 As it progresses, slightly palpable erythematous plaques appear in the mentioned areas adjacent to small papules (Figure 2). Moderate to intense pain and itching may be observed. 1 Photoallergic reactions are an immune-mediated process generally requiring more than one exposure to a given agent. 2 It is a Type IV, or delayed type, hypersensitivity reaction. 2 Solar radiation, usually in the UVA range, allows covalent binding of a drug to an endogenous protein forming a photo-antigen resulting in eczematous eruptions on the superficial dermis with no relation to area of sun exposure. 2 Common photosensitizers include plants, prescription drugs, and other chemical agents. Phytophototoxicity consists of reactions to UV light following exposure to plant matter. 5 The Apiaceae (celery) and Rutaceae (citrus) families are the most common causes of phytophototoxicity in the United States. 5 Tetracyclines are one of the most frequent photosensitizing agents. Among them, demethylchlortetracycline and doxycycline have the highest phototoxic potential, with doxy showing photopatch 5 reactivity within 15 minutes after exposure. 7 Doxycycline’s phototoxicity is independent of duration of therapy and instead is directly dose dependent, increasing from 3% risk at 100mg per day to 42% at 200mg per day. 9

Conclusions

Treatment of phototoxicity usually includes removing the offending agent and limiting UV exposure. 7,4 Symptoms should resolve within 10-14 days. 1 However, patients on these agents for a long-term basis, such as NSAIDS, amiodarone, and CCBs, 6 should be educated of the potential effects on their skin, be advised to avoid direct exposure to sunlight, and use appropriate photoprotection. If these measures are taken promptly, it is not necessary to cease treatment. 10 Topical steroids can be used to treat cases of moderate severity and extent while severe cases may require a course of systemic steroids. 2,9

Figure 2. Erythematous plaques and papules

Figure 1: Erythema on sun-exposed areas

References

Differential Diagnosis:

Acknowledgement 10. Lugović - Mihić , L, et al. Drug-induced photosensitivity – A continuing challenge. Acta Clin Croatia. 2017; 56(2): 277-283. 11. Velušček , M., et al. Doxycycline-induced photosensitivity in patients treated for erythema migrans. BMC Infectious Disease. 2018; 18(1): 365. 12. Wan, P., et al. Pellagra: a review with emphasis on photosensitivity. Br J Dermatol . 2011; 164(6): 1188. 13. Darvay, A., et al. Isoniazid induced pellagra despite pyridoxine supplementation. Clin Exp Dermatol. 1999; 24(3): 167. 14 . Brauer, J., et al. Lichenoid drug eruption. Dermatol Online J. 2009; 15(8): 13. 15. Anderson, TE. Lichen planus following quinidine therapy. Br J Dermatol. 1967; 79(8): 500. 16. Seehafer, JR., et al. Lichen planus-like lesions caused by penicillamine in primary biliary cirrhosis. Arch Dermatol. 1981; 117(3): 140. 17. Schanbacher, CF., et al. Pseudoporphyria: a clinical and biochemical study of 20 patients. Mayo Clin Proc . 2001; 76(5): 488. 1. Goetze, S, et al. Phototoxicity of doxycycline: a systematic review on clinical manifestations, frequency, cofactors, and prevention. Skin Pharmacology and Physiology . 2017; 30: 76-80. 2. Khandpur S, et al. Drug-induced photosensitivity: new insights into pathomechanisms and clinical variations through basic and applied science. Br J Dermatol. 2017; 4(176): 902-909. 3. Kim WB, et al. Drug-induced phototoxicity: a systematic review. J Am Acad Dermatol. 2018.; 79(6): 1069-1075. 4. Ibbotson S, et al. Drug and chemical induced photosensitivity from a clinical perspective. Photochemical & Photobiological Sciences . 2018; 17(12): 1885-1903. 5. Bolognia JL, Schaffer JV, Cerroni L. Dermatology . 4 th ed. Elsevier. 2018. 6. Monteiro, AF, et al. Drug-induced photosensitivity: photoallergic and phototoxic reactions. Clin in Derm . 2016; 34(5): 571- 581. 7. Bogumiła Zuba E, et al. Drug-induced photosensitivity. Acta Dermatol Croat . 2016; 24(1): 55-64. 8. Randhawa A, et al. Doxycycline photosensitivity. QJM: An International Journal of Medicine. 2018; 110(4): 259-260. 9. Nguyen TA, Krakowski AC. The “heart sign”: an early indicator of dose-dependent doxycycline-induced phototoxicity. Pediatric Dermatol . 2017; 33(2): 69-71.

- Sunburn occurs when keratinocytes are exposed to too much UVB, overwhelming the antioxidants’ ability to repair ROS damage. This leads to apoptosis. 2 Erythema is first noted three to five hours following sun exposure. The erythema typically resolves in three to seven days. Blisters heal without scarring in 7 to 10 days. Scaling, desquamation, and tanning are noted four to seven days after exposure. - Phytophotodermatitis refers to the phototoxic effects of UV exposure (erythema (with or without blistering) and delayed hyperpigmentation following) after sensitization by plants. 5 Within 2 hours of UVA exposure, desmosomes degenerate leading to blister formation. 5 Erythema, edema and bullae appear after 24 hours and peak at 72 hours. Treatment includes cleaning the site with soapy water and avoiding UV exposure. 5

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