Journal of Dermatology 2014; 41: 645–671
LETTERS TO THE EDITOR
A patient with lupus miliaris disseminatus faciei treated successfully with a combination of oral metronidazole and topical tacrolimus Dear Editor, Lupus miliaris disseminatus faciei (LMDF) is a rare granulomatous, inflammatory dermatosis of unknown etiology. It is characterized by reddish yellowish brown papules on the central face, particularly on and around the eyelids.1 There is no established therapy for LMDF due to lack of controlled study. Although many therapies, including tetracycline, oral steroids, dapsone, and topical tacrolimus are reported to be effective,2 there is no report of treatment with oral metronidazole in English literature. Herein, we report the first case of LMDF treated successfully with oral metronidazole. A 37-year-old woman visited our department with a 2-month history of almost asymptomatic eruption of the central face. She had tiny (1–3 mm), dome-shaped reddish yellow papular lesions without rash and teleangiectasia on the face including the eyelids, perioral area, forehead, and chin (Fig. 1a). Dermoscopy revealed apple-jelly nodule-like appearance (Fig. 1b). Laboratory examination, including angiotensin-converting enzyme and lysozyme, was within normal limits and the T-SPOT tuberculosis test was negative. The histopathology of papules on the right cheek revealed granulation tissue composed of central caseation necrosis surrounded by epitheloid cells (Fig. 1c). There were multinucleate giant cells of the Langhans type (Fig. 1d). The tissue was negative for Ziel-Neelsen stain. A diagnosis of LMDF was made. We had treated the patient with oral roxithromycin (150 mg twice daily) and topical tacrolimus for 1 month, however, the eruption showed no improvement. Oral metronidazole (250 mg twice daily) was then administered, while topical tacrolimus was maintained. Two weeks later, a prominent improvement was achieved. The eruptions almost disappeared with no scarring (Fig. 1e). The medication was maintained and no recurrence and side effects have occurred at 4-month follow-up. Metronidazole is a nitroimidazole antimicrobial drug. It is used both systemically and topically for many cutaneous disease, including rosacea, acne and perioral dermatitis. However, the use of oral metronidazole for treatment of LMDF has never been reported in English literature. LMDF is a distinctive disease entity of a debatable pathophysiology, and a variety of treatments have been tried and reported with variable outcomes. There are some reports of the treatment for rosacea, one of similar conditions of LMDF, by oral metronidazole.3,4 Pye et al.3 conducted a double-blind trial in 29 patients with rosacea and showed that metronidazole was therapeutically superior to a placebo after 6 weeks’ treatment. No other
Figure 1. (a) Clinical features on the first visit. (b) Dermoscopic images. Apple-jelly nodule-like appearance. (c) Granulation tissue with central caseation necrosis. (d) Langhans cells. (e) Clinical features after the treatment. patients presented side effects during the trial. Saihan et al.4 conducted a randomized double-blind trial in forty patients and showed the same effectiveness of oral metronidazole to rosacea as that of oral oxytetracycline after 6 and 12 weeks’ treatment. No side effects were reported. Although these trials provided only limited data, oral metronidazole might be a choice of treatment for rosacea and its relative conditions including LMDF. We treated the patient with oral metronidazole in combination with topical tacrolimus, therefore we can not rule out the possibility that topical tacrolimus is also effective. However, for 1 month before the introduction of metronidazole, we also had used topical tacrolimus, but the eruption showed no improvement. Therefore, we believe the oral metronidazole was most effective in our patient.
Correspondence: Hisashi Nomura, M.D., Department of Dermatology, Shizuoka Municipal Shimizu Hospital, 1231 Miyakami, Shimizu-ku Shizuoka city, Shizuoka, 424-0911, Japan. Email: [email protected]
© 2014 Japanese Dermatological Association
645
Letters to the Editor
CONFLICT OF INTEREST:
None.
Hisashi NOMURA, Shohei EGAMI, Hiroko KASAI, Tomoaki YOKOYAMA, Atsushi FUJIMOTO, Makoto SUGIURA Department of Dermatology, Shizuoka Municipal Shimizu Hospital, Shizuoka, Japan
REFERENCES 1 Borhan R, Vignn-Pennamen MD, Morel P. Lupus miliaris disseminates faciei: 6 cases. Ann Dermatol Venereol, 2005; 132: 526–530. 2 AI-Mutairi N. Nosology and therapeutic options for lupus miliaris disseminates faciei. J Dermatol, 2011; 38: 864–873. 3 Pye RJ, Burton JL. Treatment of rosacea by metronidazole. Lancet, 1976; 1: 1211–1212. 4 Saihan EM, Burton JL. A double-blind trial of metronidazole versus oxytetracycline therapy for rosacea. Br J Dermatol, 1980; 102: 443–444.
doi: 10.1111/1346-8138.12518
Giant congenital juvenile xanthogranuloma presenting as a yellowish atrophic plaque Dear Editor, Juvenile xanthogranuloma (JXG) is the most common type of non-Langerhans cell histiocytosis. Usually, JXG is an acquired red to yellow-brown papule that appears in early childhood. Atypical clinical presentations, such as plaque, subcutaneous and giant variants (>2 cm), have been reported. As such, giant JXG, usually present at birth, are very uncommon lesions, and can often be misdiagnosed as congenital hemangioma or malignant tumor.1 Herein, we report an unusual type of giant congenital JXG presenting as an atrophic plaque. A healthy 3-month-old girl was referred for a congenital lesion on her forehead. Physical examination revealed a yellowish atrophic plaque on the right side of her forehead, measuring 3 cm 9 4 cm in diameter. Venous vessels were visible through the lesion and one discrete papule at the periphery was observed (Fig. 1a). The rest of the physical examination was normal, and no
(a)
(b)
(c)
(d)
Figure 1. (a) Yellowish atrophic plaque with visible venous vessels through the lesion and one discrete papule at the periphery. (b) Panoramic view showing normal epidermis and groups of macrophages in deep dermis and hypodermis (hematoxylin– eosin [HE], original magnification 940). (c) Higher magnification showing foam cells intermingled with scarce lymphocytes and (d) eosinophils. The black arrow shows an eosinophil (HE, 9400).
other skin lesions were found. Her family history was unremarkable. A skin biopsy was performed on the atrophic plaque and showed normal epidermis and groups of macrophages in the deep dermis and hypodermis (Fig. 1b) along with a dense cellular infiltrate of foamy histiocytes intermingled with scarce lymphocytes and eosinophils (Fig. 1c,d). Immunohistochemistry was positive for CD68 and negative for S-100. The diagnosis of giant congenital JXG was made. Extracutaneous involvement was ruled out; no systemic or ocular compromise was found. The laboratory routine and abdominal ultrasonography were normal. An expectant management was decided, and the plaque has begun to regress. Giant JXG have a variety of clinical presentations. As such, infiltrative plaques, clusters of papules, large masses with papules at the periphery and an atrophic plaque, have been reported.2–5 Histologically, an infiltrate of foamy histiocytes, giant cells and intermingled lymphocytes and eosinophils are found. In our case, Touton giant cells were not found, and this feature has been previously reported in immature lesions of giant congenital JXG.1 The atrophic pattern of our case can be explained by the fact that the infiltrate was located in the deep dermis and hypodermis associated with a decrease amount of subcutaneous fat. Also, the presence of fibrosis, which suggests regression, was seen in the dermis. The differential diagnosis includes subcutaneous fat necrosis presented in newborns that develop multiple indurated nodules after trauma or asphyxia during birth. Histologically, a lobular panniculitis with areas of fat necrosis that are infiltrated by macrophages and multinucleated giant cells, which contain crystalline arrays of fat are found. Extracutaneous involvement occurs in 5% of cases, and the eye represents the most affected site.4,5 In the cases of only cutaneous lesions, the prognosis is excellent, and a “wait-andsee” strategy is recommended. Spontaneous regression occurs within 6 months to 3 years, but JXG may leave hyperpigmentation, anetoderma and atrophic scars.2,4 We would like to highlight that giant JXG has a myriad of clinical presentations, which make its diagnosis a challenge. Giant JXG can present as an atrophic plaque at birth, so its recognition and differentiation from other pathologies can avoid unnecessary excision or any aggressive procedures for this benign condition.
Correspondence: Fabiola Schafer Villalobos, M.D., 115 Claro solar Street, Temuco 123, Chile. Email: [email protected]
646
© 2014 Japanese Dermatological Association
LETTERS TO THE EDITOR
A patient with lupus miliaris disseminatus faciei treated successfully with a combination of oral metronidazole and topical tacrolimus Dear Editor, Lupus miliaris disseminatus faciei (LMDF) is a rare granulomatous, inflammatory dermatosis of unknown etiology. It is characterized by reddish yellowish brown papules on the central face, particularly on and around the eyelids.1 There is no established therapy for LMDF due to lack of controlled study. Although many therapies, including tetracycline, oral steroids, dapsone, and topical tacrolimus are reported to be effective,2 there is no report of treatment with oral metronidazole in English literature. Herein, we report the first case of LMDF treated successfully with oral metronidazole. A 37-year-old woman visited our department with a 2-month history of almost asymptomatic eruption of the central face. She had tiny (1–3 mm), dome-shaped reddish yellow papular lesions without rash and teleangiectasia on the face including the eyelids, perioral area, forehead, and chin (Fig. 1a). Dermoscopy revealed apple-jelly nodule-like appearance (Fig. 1b). Laboratory examination, including angiotensin-converting enzyme and lysozyme, was within normal limits and the T-SPOT tuberculosis test was negative. The histopathology of papules on the right cheek revealed granulation tissue composed of central caseation necrosis surrounded by epitheloid cells (Fig. 1c). There were multinucleate giant cells of the Langhans type (Fig. 1d). The tissue was negative for Ziel-Neelsen stain. A diagnosis of LMDF was made. We had treated the patient with oral roxithromycin (150 mg twice daily) and topical tacrolimus for 1 month, however, the eruption showed no improvement. Oral metronidazole (250 mg twice daily) was then administered, while topical tacrolimus was maintained. Two weeks later, a prominent improvement was achieved. The eruptions almost disappeared with no scarring (Fig. 1e). The medication was maintained and no recurrence and side effects have occurred at 4-month follow-up. Metronidazole is a nitroimidazole antimicrobial drug. It is used both systemically and topically for many cutaneous disease, including rosacea, acne and perioral dermatitis. However, the use of oral metronidazole for treatment of LMDF has never been reported in English literature. LMDF is a distinctive disease entity of a debatable pathophysiology, and a variety of treatments have been tried and reported with variable outcomes. There are some reports of the treatment for rosacea, one of similar conditions of LMDF, by oral metronidazole.3,4 Pye et al.3 conducted a double-blind trial in 29 patients with rosacea and showed that metronidazole was therapeutically superior to a placebo after 6 weeks’ treatment. No other
Figure 1. (a) Clinical features on the first visit. (b) Dermoscopic images. Apple-jelly nodule-like appearance. (c) Granulation tissue with central caseation necrosis. (d) Langhans cells. (e) Clinical features after the treatment. patients presented side effects during the trial. Saihan et al.4 conducted a randomized double-blind trial in forty patients and showed the same effectiveness of oral metronidazole to rosacea as that of oral oxytetracycline after 6 and 12 weeks’ treatment. No side effects were reported. Although these trials provided only limited data, oral metronidazole might be a choice of treatment for rosacea and its relative conditions including LMDF. We treated the patient with oral metronidazole in combination with topical tacrolimus, therefore we can not rule out the possibility that topical tacrolimus is also effective. However, for 1 month before the introduction of metronidazole, we also had used topical tacrolimus, but the eruption showed no improvement. Therefore, we believe the oral metronidazole was most effective in our patient.
Correspondence: Hisashi Nomura, M.D., Department of Dermatology, Shizuoka Municipal Shimizu Hospital, 1231 Miyakami, Shimizu-ku Shizuoka city, Shizuoka, 424-0911, Japan. Email: [email protected]
© 2014 Japanese Dermatological Association
645
Letters to the Editor
CONFLICT OF INTEREST:
None.
Hisashi NOMURA, Shohei EGAMI, Hiroko KASAI, Tomoaki YOKOYAMA, Atsushi FUJIMOTO, Makoto SUGIURA Department of Dermatology, Shizuoka Municipal Shimizu Hospital, Shizuoka, Japan
REFERENCES 1 Borhan R, Vignn-Pennamen MD, Morel P. Lupus miliaris disseminates faciei: 6 cases. Ann Dermatol Venereol, 2005; 132: 526–530. 2 AI-Mutairi N. Nosology and therapeutic options for lupus miliaris disseminates faciei. J Dermatol, 2011; 38: 864–873. 3 Pye RJ, Burton JL. Treatment of rosacea by metronidazole. Lancet, 1976; 1: 1211–1212. 4 Saihan EM, Burton JL. A double-blind trial of metronidazole versus oxytetracycline therapy for rosacea. Br J Dermatol, 1980; 102: 443–444.
doi: 10.1111/1346-8138.12518
Giant congenital juvenile xanthogranuloma presenting as a yellowish atrophic plaque Dear Editor, Juvenile xanthogranuloma (JXG) is the most common type of non-Langerhans cell histiocytosis. Usually, JXG is an acquired red to yellow-brown papule that appears in early childhood. Atypical clinical presentations, such as plaque, subcutaneous and giant variants (>2 cm), have been reported. As such, giant JXG, usually present at birth, are very uncommon lesions, and can often be misdiagnosed as congenital hemangioma or malignant tumor.1 Herein, we report an unusual type of giant congenital JXG presenting as an atrophic plaque. A healthy 3-month-old girl was referred for a congenital lesion on her forehead. Physical examination revealed a yellowish atrophic plaque on the right side of her forehead, measuring 3 cm 9 4 cm in diameter. Venous vessels were visible through the lesion and one discrete papule at the periphery was observed (Fig. 1a). The rest of the physical examination was normal, and no
(a)
(b)
(c)
(d)
Figure 1. (a) Yellowish atrophic plaque with visible venous vessels through the lesion and one discrete papule at the periphery. (b) Panoramic view showing normal epidermis and groups of macrophages in deep dermis and hypodermis (hematoxylin– eosin [HE], original magnification 940). (c) Higher magnification showing foam cells intermingled with scarce lymphocytes and (d) eosinophils. The black arrow shows an eosinophil (HE, 9400).
other skin lesions were found. Her family history was unremarkable. A skin biopsy was performed on the atrophic plaque and showed normal epidermis and groups of macrophages in the deep dermis and hypodermis (Fig. 1b) along with a dense cellular infiltrate of foamy histiocytes intermingled with scarce lymphocytes and eosinophils (Fig. 1c,d). Immunohistochemistry was positive for CD68 and negative for S-100. The diagnosis of giant congenital JXG was made. Extracutaneous involvement was ruled out; no systemic or ocular compromise was found. The laboratory routine and abdominal ultrasonography were normal. An expectant management was decided, and the plaque has begun to regress. Giant JXG have a variety of clinical presentations. As such, infiltrative plaques, clusters of papules, large masses with papules at the periphery and an atrophic plaque, have been reported.2–5 Histologically, an infiltrate of foamy histiocytes, giant cells and intermingled lymphocytes and eosinophils are found. In our case, Touton giant cells were not found, and this feature has been previously reported in immature lesions of giant congenital JXG.1 The atrophic pattern of our case can be explained by the fact that the infiltrate was located in the deep dermis and hypodermis associated with a decrease amount of subcutaneous fat. Also, the presence of fibrosis, which suggests regression, was seen in the dermis. The differential diagnosis includes subcutaneous fat necrosis presented in newborns that develop multiple indurated nodules after trauma or asphyxia during birth. Histologically, a lobular panniculitis with areas of fat necrosis that are infiltrated by macrophages and multinucleated giant cells, which contain crystalline arrays of fat are found. Extracutaneous involvement occurs in 5% of cases, and the eye represents the most affected site.4,5 In the cases of only cutaneous lesions, the prognosis is excellent, and a “wait-andsee” strategy is recommended. Spontaneous regression occurs within 6 months to 3 years, but JXG may leave hyperpigmentation, anetoderma and atrophic scars.2,4 We would like to highlight that giant JXG has a myriad of clinical presentations, which make its diagnosis a challenge. Giant JXG can present as an atrophic plaque at birth, so its recognition and differentiation from other pathologies can avoid unnecessary excision or any aggressive procedures for this benign condition.
Correspondence: Fabiola Schafer Villalobos, M.D., 115 Claro solar Street, Temuco 123, Chile. Email: [email protected]
646
© 2014 Japanese Dermatological Association
