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Pimecrolimus 1 percent cream and pulsed dye laser in treatment of a patient with reticular erythematous mucinosis syndrome

  • Author(s): Mansouri, Parvin
  • Farshi, Susan
  • Nahavandi, Arezo
  • Safaie-Naraghi, Zahra
  • et al.
Main Content

Pimecrolimus 1 percent cream and pulsed dye laser in treatment of a patient with reticular erythematous mucinosis syndrome
Parvin Mansouri1, Susan Farshi1, Arezo Nahavandi2, Zahra Safaie-Naraghi3
Dermatology Online Journal 13 (2): 22

1. Department of dermatology, Tehran University of Medical Sciences, Imam Hospital, Gharib St, Keshavarz Blvd, Tehran, Iran. sfarshi@razi.tums.ac.ir 2. Department of physiology and pharmacology, Iran University of Medical Sciences, Hemat Highway, Tehran, Iran 3. Department of pathology, Tehran University of Medical Sciences, Razi Skin Hospital, Vahdat St, Tehran, Iran

Abstract

We report on the efficacy of twice daily application of pimecrolimus 1 percent cream in a 48-year-old woman with reticular erythematous mucinosis (REM) syndrome and compare its results with pulsed dye laser (PDL) on the other side of her chest and back. The patient was previously treated by hydroxychloroquine but only a fair response was observed. After application of 5 months of pimecrolimus, the lesions completely resolved and the result was comparable with the other side of her body treated by pulsed dye laser. Topical pimecrolimus and pulsed dye laser appear to be effective and safe treatments for REM.


Reticular erythematous mucinosis (REM) syndrome has been described by Steigleder et al in 1974 [1]. Reticular erythematous mucinosis syndrome is a rare disorder that affects patients of all ages and both sexes, but most cases are middle aged women [2, 3]. This syndrome is characterized by pink reticulate or sheet-like erythema on the central part of the chest and back and is generally symmetrical [2, 3, 4, 5]. The clinical course is cyclic with remission and exacerbation [3]. Affected patients are frequently asymptomatic. However, in 20-30 percent of cases pruritus is reported [2]. Mucous membranes, genitalia, and internal organs are not involved, but in 1977 Keczkes and Jadhav reported a case with gum involvement and cervical lymphadenopathy [6]. Photosensitivity is often noticed and sunlight exposure has been reported to induce new lesions or to aggravate the condition and produce symptoms of burning and pruritus [2, 3]. However, in several cases it has been difficult to produce the eruption by phototesting with UVB and UVC in previously uninvolved areas [7, 8, 9]. There are a few reports linking the rash to hormonal status showing deterioration of REM syndrome in association with the oral contraceptives (OCP), during pregnancy, and exacerbation during menstruation [10].

Characteristic histologic features are a perivascular, and occasionally perifollicular, mononuclear cell infiltrate with increased dermal mucin deposition. The epidermis appears normal [1-11]. Direct immunofluorescence is usually negative for immunoglobulins, fibrin, and complement, although a few cases of REM with positive direct immunofluorescence and granular deposits of immunoglobulin IgM and C3 have been reported [5, 8, 9].

The etiology of REM remains unknown [3, 5]. Some consider it part of the broad spectrum of lupus erythematous-like diseases. The two share some common features such as flare after exposure to ultraviolet radiation, clinical manifestations, histology, and good response to systemic antimalarials [2, 3, 4]. Reticular erythematous mucinosis may be related to alteration in immune function; there has been an association with autoimmune diseases [5]. Coexisting disorders reported in association with occasional cases of REM syndrome include systemic lupus erythematosus, discoid lupus erythematosus, hyperthyroidism, Hashimoto's disease, diabetes mellitus, carcinoma, thrombocytopenic purpura, myopathy, and polyneuropathy [5, 11, 12]. In 1995 Dauden et al. reported a case of reticular erythematous mucinosis in a patient who also had human immunodeficiency virus (HIV) infection [13].

Pimecrolimus is a medication in the new class of immunomodulating macrolactams and it has significant anti-inflammatory activity and low systemic immunosuppressive potential [14, 15]. Flashlamp-pumped pulsed dye laser was specifically developed for the treatment of cutaneous vascular lesions. In the study of Greve and Raulin, treatment of REM syndrome by PDL was successful [16]. We therefore investigated the efficacy of pimecrolimus in a woman who had REM syndrome of her chest, upper back, and arms; we compared the results with pulsed dye laser (PDL) for her symmetrical lesions.


Clinical synopsis

A 48-year-old woman had an 8-year history of asymptomatic slightly palpable erythematous eruption bilaterally on her anterior chest wall and similar lesions on her upper back and arms. Sometimes the lesions became itchy. There was no family history of such skin manifestations. Skin examination showed erythematous macules, papules, and plaques on her chest, back, clavicular area, and arms (Figs. 1 and 2).


Figure 1Figure 2
Figure 1. Chest involvement of the affected woman with REM syndrome
Figure 2. Upper back involvement of the affected woman with REM syndrome

Routine laboratory tests were within normal limits. Antinuclear antibody (ANA), Anti Ds DNA, and LE cells were not found. A skin biopsy from the back was obtained. A slightly flattened epidermis with vascular dilatation associated with a mononuclear perivascular infiltrate consisting mostly of lymphocytes admixed with a few histiocytes and neutrophils was observed. Separation of dermal collagen bundles with homogenous material in the upper and mid dermis is exhibited (Figs. 3A and 3B). Excess mucin, predominantly hyaloronic acid, was present in the upper and mid dermis (Figs. 4A and 4B). Direct immunofluorescence showed only a few IgM positive cytoid bodies in the papillary dermis.

Reticular erythematous mucinosis syndrome was diagnosed. About 3 years prior, the patient had received hydroxychloroquine 200 mg twice daily for 1 month after normal ophthalmological examination. The dose was then reduced to once daily for 2 months, but only a fair response was observed and she discontinued the treatment due to side effects.


Figure 3AFigure 3B
Figure 3. Skin biopsy from the upper back by Hematoxyline-Eosin stain using light microscopy at a magnification of (A) 10X, (B) 40x.

Figure 4AFigure 4B
Figure 4. Toluidine blue and alcian blue stain of the same biopsy specimen at a magnification of (A) 10x, (B) 40x

We began therapy with pimecrolimus cream 1 percent (Elidel 1%, Novartis pharmaceuticals, Switzerland) twice daily on the right side of her body. After 5 months application of pimecrolimus cream 1 percent twice daily, the lesions nearly completely resolved (Figs. 5 and 6). No side effects were observed.


Figure 5Figure 6
Figure 5. Chest area after twice daily application of pimecrolimus 1% cream for 5 months on the right side and 2 sessions PDL on the left side.
Figure 6. Upper back area after twice daily application of pimecrolimus 1% cream for 5 months in the right side and 2 sessions PDL in the left side.

Figure 7
Figure 7. Test area by pulsed dye laser (PDL) on the upper back

We treated the lesions of the left side by pulsed dye laser. An initial test treatment in 2.5 cm² was carried out on her back (Fig. 7). The flashlamp-pulsed dye laser (SLS, England) was used at the wavelength of 585 nm and pulse duration of 450 ms. The applied energy density was 4.8 J/cm² with a spot size of 5 mm. Two Laser sessions were used with a 2 month interval. Anesthesia was not necessary. The patient was very satisfied with the result (Figs. 5 and 6).


Conclusion

The pathologic mechanism of REM syndrome is unclear but various theories have been discussed such as an immune mechanism of disease due to its association with autoimmune diseases [2, 3, 5, 16]. The net-like erythema is found on the central chest and back and is occasionally accompanied by itching. The syndrome has been documented more frequently in women than in men and the syndrome initially appeared between the ages of 11 and 40 years in 80 percent of women and 63 percent of men. The syndrome rarely arises before age 10 or after age 60 years [9]. Histologic findings include dilated dermal vessels with lymphocytic perivascular infiltration and alcian blue positive deposition [2-11, 16].

Until now, hydroxychloroquine 200-400 mg daily is the treatment of choice. In a subject not responsive to systemic antimalarials or with contraindications for these drugs, no alternative therapy was hitherto available [2, 9]. Relapses often occur [16]. There are a few reports that examined other treatment options for REM syndrome [2, 16]. Rubegni et al. in 2004 reported a case successfully treated by tacrolimus [2]. Tacrolimus exerts a potent immunosuppressive effect on T cells by blocking the action of calcineurin [17]. Pimecrolimus is one of the new classes of immunomodulating macrolactams and was specifically developed for the treatment of inflammatory skin diseases. The mechanism of action of pimecrolimus is the blockage of T cell activation and inhibition of the synthesis of inflammatory cytokines [14, 15]. We treated our patient with REM syndrome both by application of pimecrolimus 1 percent cream and pulsed dye laser. In both sides the affected areas nearly completely resolved clinically.

Successful treatment of REM syndrome by pulsed dye laser (PDL) has been reported [16]. It was also effective in other inflammatory skin diseases such as extragenital lichen sclerosus et atrophicus and lupus erythematosus [16, 18]. PDL is pulsed at 450 µsec with a wavelength of 585 nm, which makes the primary target chromophore hemoglobin, which is the reason it is mainly used in the treatment of vascular conditions such as port-wine stains, hemangiomas, and telangiectasis [16-19]. It works according to the principles of selective photothermolysis, damaging dermal vessels to the depth of 1.2-1.5 mm [16]. PDL is safe and and has few side effects [16, 18]. In the REM syndrome, mucin and lymphocytic infiltrate are histologically proven to be reduced by the laser's effects. The mechanisms remain unknown and may be related to damaging small blood vessels and activating immunologic processes [16].

In conclusion, both pimecrolimus 1 percent cream and PDL were found to be safe and valid alternative treatment in our patient.

References

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