INTRODUCTION

Reticular erythematous mucinosis (REM) is an idiopathic disorder of primary dermal mucin accumulation, a rare form of cutaneous mucinosis [1–3]. It most often involves the midline of the upper chest or back in middle-aged women. Other atypical parts involve the face, abdomen, neck, and limbs. It typically presents with erythematous macules and papules that coalesce into a reticulated pattern [4]. The etiology and pathophysiology have been poorly identified; nonetheless, correlations have been observed with other autoimmune disorders such as systemic lupus erythematosus (SLE), scleroderma, thyroid disease, and various types of cancers. The triggering factors include smoking, hormonal disturbances, menstrual cycle, sunlight, and UV radiation [5,6]. There is still an exciting ongoing scientific debate regarding the relation to cutaneous lupus erythematosus (CLE) as they share a clinical and histopathologic resemblance. However, there were identified some histological differences in our case report [7]. Early recognition and diagnosis of REM is important as it will differentiate it from other autoimmune dermatoses such as CLE and will, therefore, offer a different prognosis, systemic involvement, and disease progression [5–7]. Herein, we report the case of a 48-year-old female patient with an atypical variant of REM on the upper extremity that was found to be correlated with her thyroid disease and was exacerbated during her premenstrual period. She mentions a similar clinical presentation twenty-four years ago where no diagnosis was established and was partially improved with topical corticosteroids. The history of autoimmune thyroid disease in our case lent further credence to immune function dysregulation as a potential etiology of REM. In our case, we confirm that the antimalarial treatment remains the mainstay of treatment of REM. Ultimately, a close correlation of dermatologic and histologic findings was required to produce a diagnosis in this case and highlights the need for clinical and pathologic correlation in dermatology, especially in cases with atypical and recalcitrant presentations.

CASE REPORT

This is a case of a 48-year-old female patient presenting in September 2023 at our hospital with a long-standing undiagnosed exanthema in her left forearm. Clinically, there were unilateral reticulated and indurated erythro-violaceous papules in the anterior lower part of the left forearm, which were itchy, photosensitive, and deteriorating with light and during the premenstrual period (Figs. 1a and 1b). During history taking, she mentioned there were two to three erythematous plaques initially in the same area over the last four years, which were previously managed as either neurodermatitis with topical corticosteroids with no satisfactory resolution or fungal infection that was unsuccessfully treated as such. She also mentioned that the erythematous plaques first appeared twenty-four years ago, which were managed with minimal improvement as dermatitis with topical corticosteroid. Regarding her medical history, she had iron-deficiency anemia due to menorrhagia, for which she was receiving iron supplements, and a history of thyroid CA, for which she had a total thyroidectomy in 2008 and treatment with iodine. After that, she developed hypothyroidism for which she was receiving T4 per os. Fungal cultures from direct examination and cultivation were negative. From the serological investigations microscopic-microcytic anemia was revealed, as expected from the history given and immunological investigations, including anti-dsDNA, anti-Ro, anti-LA, ANA, anti-Centromere, anti-Sm and anti-CCP, which were normal. We took a punch biopsy from the left forearm with a wide range of differential diagnosis, including lichen nitidus, granulomatous disease (granuloma annulare, cutaneous sarcoidosis), cutaneous lupus, lupus tumidus, Jessner’s lymphocytic infiltrate, polymorphic light eruption, malignant atrophic papulosis, plaque stage mycosis fungoides and reticular erythematous mucinosis. Histology with H&E stain revealed predominantly tense perivascular infiltration by small lymphocytes at the level of the reticular dermis (Figs. 2a and 2b). There was focal mucus deposition in the dermis (Alcian blue) and a normal epidermis. Immunohistochemistry revealed T lymphocytes with CD2⁺, CD3⁺, CD4⁺, CD5⁺, CD7⁺ more than CD8⁺, TCRδ- and a low Ki67/MiB1 cell proliferation index around 5%. The above findings were consistent with the diagnosis of reticular erythematous mucinosis [6–8]. Therefore, we initiated treatment with photoprotection, topical clobetasol propionate 0.05% cream twice daily for a month followed by Tacrolimus 0.1% ointment twice daily for three months (Fig. 3). Following the concurrent opinion of her hematologist and ophthalmologist as per initiation protocol, we started hydroxychloroquine 200 mg twice daily [9,10]. We noticed complete clearance of all lesions within two months with the above treatment. Following a trial to reduce hydroxychloroquine to once daily at three months, she mentioned minor irritation in the area during her premenstrual period, thus we maintained the dosage twice daily, and on the six- and eight-month follow-ups, she remained free of any exanthema (Fig. 4).

	Figure 1: (a) Clinical picture at first review. Unilateral reticulated and indurated erythro-violaceous papules in the anterior lower part of the left forearm, biopsy site. (b) Indurated erythematous papules and plaques on the left forearm at first review.
	Figure 2: (a) Histopathology. Focal mucus deposition in the dermis (Alcian blue). (b) Histopathology. Tense perivascular infiltration by small lymphocytes at the level of the reticular dermis (H&E stain).
	Figure 3: Three weeks follow-up following the use of photoprotection and topical clobetasol propionate 0.05% twice daily.
	Figure 4: Complete clinical resolution at six months follow-up following treatment with hydroxychloroquine.

DISCUSSION

REM is a rare form of diffuse cutaneous mucinosis with a poorly identified pathophysiology [1,2]. It usually affects patients in early adulthood and commonly women. Clinically, it is characterized by an asymptomatic, or occasionally pruritic, macular, and reticulated erythematous exanthem typically on the central chest and upper back [3]. Occasionally, however, it may occur on the abdomen, face, and the proximal upper extremities [4]. Exposure to sunlight typically increases the burning sensation on the affected site in most patients. The suggested etiology includes UV radiation, autoimmune diseases, viral infections, and Borrelia infection. It has been associated with withdrawal syndrome from alcohol, SSRIs, or TCAs. The factors that aggravate the disease could be menstruation, pregnancy, hormonal disturbances, hyperhidrosis, and exposure to heat or radiation. The main diagnostic challenge is its differentiation from cutaneous lupus erythematosus since they share similar clinical picture responses to antimalarials, both including photosensitivity and female predominance. Distinguishing them, we should take into consideration that REM lacks antinuclear antibodies and histologically shows mainly lymphocytic infiltration of the dermis and mucin deposition limited to the dermis as opposed to CLE, where there is infiltration of the dermis with a variety of inflammatory cells and extension of the mucin deposition to the subcutaneous tissue, respectively, and additionally, one may observe epidermal atrophy and follicular hyperkeratosis. As mentioned before, the histology in our case was characteristic of REM. Typically, there is perivascular and perifollicular infiltrate, composed primarily of lymphocytes throughout the upper dermis. Fibroblasts are normal in number and appearance, and fibroblasts are normal in number and appearance. Collagen fibers appear similarly unchanged despite diffuse upper dermal edema and mucin deposition. The rapid response to hydroxychloroquine in our case mirrors the up-to-date evidence we have that antimalarial drugs remain the mainstay of treatment from REM [8,9]. Various other treatments that have been mentioned in the literature are corticosteroids, calcineurin inhibitors, tetracycline, antihistamines, UVA-UVB phototherapy, cyclosporine, and dapsone; nevertheless, limited response has been seen in the past [8–12]. According to previous case reports, and as seen in our case, a trial to reduce antimalarials or stop the treatment might trigger a relapse of the disease. Automatic regression of lesions may be seen even fifteen years after the onset of the condition.

CONCLUSION

To summarize, we presented a rare case of a middle-aged woman with REM observed in an atypical body part, more specifically the arms, which was previously unsuccessfully treated as dermatitis. The histology revealed the diagnosis, and treating the patient with hydroxychloroquine, we noticed complete resolution of the exanthema. Most importantly, this case highlights the need for a biopsy where there is diagnostic doubt and resistance to treatment in patients with dermatological rashes. Additionally, in this case, there seemed to be an association with hypothyroidism as previously described in the literature. We enhance this association and urge the scientific community to investigate the conjunction of REM to thyroid auto-antibodies further. A well-controlled thyroid function could improve the symptoms of REM. Moreover, we confirm, to an extent, the connection of REM to menstrual cycle change. Most likely, there is an association with the hormonal changes in the body during the menstrual cycle, and that could be further looked into in the future. In conclusion, the success of antimalarials as a first-line therapy of REM was attested in our case while only limited response to topical corticosteroids was observed.

Consent

Clinical research is based on the Declaration of Helsinki. All personal details of the patients are kept confidential.

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