Chromate-Induced Allergic Contact Dermatitis Treated With Dupilumab

Chromate causes persistent, difficult to treat irritant and allergic contact dermatitis in cement-handling occupational workers. When therapeutics such as topical corticosteroids, topical calcineurin inhibitors, phototherapy and immune-modulating treatments like methotrexate fail, many patients are advised that avoidance may be the only remaining option – an option that may be particularly challenging if the patient’s occupation necessitates chromate exposure. JDD authors Britney N. Wilson MBS, Esther A. Balogh MD, David J. Rayhan MD, Paul K. Shitabata MD, Daniel J. Yousefzadeh BA, and Steven R. Feldman MD PhD, rereport a case of severe chromate-induced allergic contact dermatitis in a 55-year-old cement mason that presented to the outpatient dermatology clinic with multiple scaly, erythematous, >5 cm plaques scattered over the skin of his hands, head and neck. After a prior failed course of treatment with high potency topical corticosteroid, this patient was successfully treated with dupilumab. Given the success of dupilumab in their patient, the authors propose the consideration of dupilumab as an alternative treatment option for those suffering from chromate-induced allergic contact dermatitis that is refractory to ultra-high potency topical corticosteroids.

Introduction

Chromate, an anion of chromium and oxygen discovered by Vaquelin in 1798, is a common cause of occupational skin disease.¹ The prevalence of chromium sensitivity in the general U.S. population ranges from 0.08 to 7%.² Chromium can cause both irritant contact dermatitis and, more frequently, allergic contact dermatitis (ACD).³ Nickel(II) ion is the most frequent cause of type IV hypersensitivity reactions, accounting for 23% of all cases diagnosed by patch testing, followed by cobalt(II) ion (9.3%) and hexavalent chromium (chromium[VI]) (5.6%).⁴Chromate is frequently used in plating, leather tanning, pigmentation, dye production, and chemical industries, and is found in cement as a byproduct of the cement manufacturing process.⁵ Approximately one-third of bricklayers and stonemasons who are in frequent contact with cement, as well as one in ten metal operators who have an occupational disorder, received a diagnosis of contact dermatitis due to hexavalent chromium exposure.^4,6,7

Case

A 55-year-old Hispanic male patient presented to the outpatient dermatology clinic in October 2018 with intractable dermatitis. Scaly, erythematous, >5 cm plaques were present on the exposed skin of his hands, head and neck (Figure 1). Areas covered by clothing generally showed no lesions. History revealed that the patient worked as a cement mason, and the areas with the aforementioned skin findings were present only at the areas exposed to cement dust. The patient reported little to no improvement in the past with ultra-high potency topical corticosteroids.

Chromate-Induced Allergic Contact Dermatitis — FIGURE 1. Scaly, erythematous, >5 cm plaques are present on the exposed skin of the patient’s hands.

The patient’s past medical history was significant for bronchitis, a congenitally missing kidney, and hepatitis C infection that was successfully treated with anti-viral therapy. Past surgical history was significant for a left lung lobectomy secondary to bronchitis. The patient denied any concurrent medications other than topical corticosteroids. A 12-point review of systems was positive for bronchitis, chronic intermittent cough for which he is followed by his pulmonologist and primary care physician, and hypertension. A skin biopsy was performed at his right ventral forearm, revealing scattered melanophages with superficial perivascular and interstitial lymphocytic infiltrate, consistent with a diagnosis of contact dermatitis (Figures 2-3).

Chromate-Induced Allergic Contact Dermatitis Treated With Dupilumab — FIGURE 2. Low power photomicrograph of the patient’s biopsy from the
right ventral forearm. There are spongiotic vesicles in the epidermis
and a superficial mononuclear perivascular infiltrate (4x magnification).

Given the frank presentation and history of dermatitis only in areas where the patient was exposed to cement dust, the patient was not patch tested for chromium. Because he had not shown any clinical improvement in the past with ultra-high potency topical steroids, topical therapy was not reattempted. Due to his past history of viral hepatitis, methotrexate was considered but ultimately not pursued as a treatment option. Consequently, the patient was started on dupilumab, and received one loading dose of 600 mg. After a misinterpretation of the recommended dosing, the patient continued the 600 mg dose every two weeks for 2 months, at which time he presented for a follow up visit at which his dupilumab dose was decreased to 300 mg every two weeks. At that point, the patient’s dermatitis had completely resolved (Figure 4), and he reported no adverse events (and, in particular, no conjunctivitis) throughout the treatment course. Though the patient’s occupational exposure to chromate as a cement mason did not change, the patient’s dermatitis remained clear for the next 18 months to date (July 2020).

Discussion

Clinically, chromate allergy appears as a severe, sometimes widespread, very persistent dermatitis, and is considered to have a relatively poor prognosis, often with therapeutic recalcitrance.⁷ Commonly used treatments for chromate induced ACD include emollients, topical corticosteroids, and topical calcineurin inhibitors.

Treatments for persistent or severe chromate-induced contact dermatitis include phototherapy and immune-modulating treatments such as azathioprine, cyclosporin and methotrexate. Until recently, when these options failed, avoidance was the only long-term management strategy available, often with negative ramifications on the livelihoods of patients who are occupationally exposed to chromate.

The case we present provides a novel treatment approach for a rare form of ACD that has the ability to significantly impact the quality of life of those affected. Dupilumab is commonly used in the treatment of atopic dermatitis (AD), a helper T-cell 2 (TH2) axis-predominant immune disorder. Dupilumab acts as an IL-4 receptor antagonist and prevents the IL-4 and IL-13- mediated inflammatory responses seen in AD. Although ACD is considered predominantly a helper T-cell 1 (TH1)-mediated process, certain allergens sensitize via the induction of the TH2 pathways.^8,9 Dupilumab may be effective in the inhibition of allergens that elicit a TH2-mediated, IL-4 dependent ACD.⁸The ability of dupilumab to treat chromate-induced ACD in our patient also suggests that IL-4 or IL-13 may play a role in ACD. The role of IL-4 in ACD was confirmed in IL-4 knockout mice, which still have the ability to elicit contact sensitivities to oxazolone but not 2,4,6-trinitrochlorobenzene, a contact allergen with a TH2-mediated sensitization pathway.^8,10Dupilumab may be an alternative treatment option for those suffering from chromiuminduced ACD that is recalcitrant to even ultra-high potency topical corticosteroids.

Disclosures

Steven Feldman has received research, speaking and/or consulting support from a variety of companies including Galderma, GSK/Stiefel, Almirall, Leo Pharma, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Valeant, Abbvie, Samsung, Janssen, Lilly, Menlo, Merck, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate, and National Psoriasis Foundation. He is founder and majority owner of www.DrScore.com and founder and part owner of Causa Research, a company dedicated to enhancing patients’ adherence to treatment.

References

1. Burrows D , Calnan CD. Cement dermatitis. II. Clinical aspects. Trans St Johns Hosp Dermatol Soc. 1965;51:27-39.
2. Wilbur S, Abadin H, Fay M, Yu D, Tencza B, Ingerman L et al. Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological Profiles. Toxicological Profile for Chromium. Atlanta (GA): Agency for Toxic Substances and Disease Registry (US); 2012.
3. Sharma AD. Low chromate diet in dermatology. Indian J Dermatol. 2009;54:293-5.
4. Buters J , Biedermann T. Chromium(VI) Contact Dermatitis: Getting Closer to Understanding the Underlying Mechanisms of Toxicity and Sensitization! J Invest Dermatol. 2017;137:274-7.
5. Costa M , Klein CB. Toxicity and carcinogenicity of chromium compounds in humans. Crit Rev Toxicol. 2006;36:155-63.
6. Bruynzeel DP, Diepgen TL, Andersen KE, Brandao FM, Bruze M, Frosch PJ et al. Monitoring the European standard series in 10 centres 1996-2000. Contact Derm. 2005;53:146-9.
7. Bregnbak D, Thyssen JP, Zachariae C , Johansen JD. Characteristics of chromium-allergic dermatitis patients prior to regulatory intervention for chromium in leather: a questionnaire study. Contact Derm. 2014;71:338-47.
8. Machler BC, Sung CT, Darwin E , Jacob SE. Dupilumab use in allergic contact dermatitis. J Am Acad Dermatol. 2019;80:280-1.e1.
9. Kohli N , Nedorost S. Inflamed skin predisposes to sensitization to less potent allergens. J Am Acad Dermatol. 2016;75:312-7.e1.
10. Dieli F, Sireci G, Scire E, Salerno A , Bellavia A. Impaired contact hypersensitivity to trinitrochlorobenzene in interleukin-4-deficient mice. J Immunol. 1999;98:71-9.

Source

Wilson, B., Balogh, E., Rayhan, D., Shitabata, P., Yousefzadeh, D., & Feldman, S. (2021). Chromate-Induced Allergic Contact Dermatitis Treated With Dupilumab. Journal of drugs in dermatology: JDD, 20(12), 1340-1342.

Content and images used with permission from the Journal of Drugs in Dermatology.

Adapted from original article for length and style.

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