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Necrobiotic xanthogranuloma of extremities in an elderly patient successfully treated with low-dose prednisolone

  • Author(s): Kawakami, Yoshio
  • Yamamoto, Toshiyuki
  • et al.
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Letter: Necrobiotic xanthogranuloma of extremities in an elderly patient successfully treated with low-dose prednisolone
Yoshio Kawakami MD PhD, Toshiyuki Yamamoto, MD PhD
Dermatology Online Journal 17 (6): 13

Fukushima Medical University School of Medicine, Hikarigaoka, Japan, Fukushima. kawayoshio@yahoo.co.jp

Abstract

We describe a 93-year-old Japanese woman who developed a painful yellowish plaque with reddish border on her left lower leg. Histological evaluation demonstrated hyaline necrobiosis and granulomatous lesions composed of histiocytes (some with foamy cytoplasm), multinucleated giant cells, and numerous cholesterol crystals. Serum electrophoresis displayed the presence of an M-peak with IgG λ paraproteinemia. There was progressive ulcer formation in the location of the biopsy on the left leg. Multiple tender red dermal and subcutaneous skin nodules developed on her extremities. Oral administration of prednisolone 20 mg daily (0.5 mg/kg) was started. After 4 weeks, she obtained resolution of the skin lesions.


Necrobiotic xanthogranuloma (NXG) is a chronic granulomatous disorder first described by Kossard and Winkelmann in 1980 [1]. It is characterized by yellowish indurated plaques and nodules, which often ulcerate. The age at onset has been reported to be 17 to 85 years with the average of 54 to 56 years. There is a predilection for the periorbital region followed by the face, trunk, and extremities [2]. The destinctive histological changes of NXG include large areas of necrobiosis alternating with granulomatous inflammation both in the deeper dermis and in the subcutaneous fat. In addition the presence of numerous cholesterol crystals, histiocytes with foamy cytoplasm, and multinucleated giant cells is characteristic [3]. The exact pathogenesis of NXG remains unknown, although paraproteinemia is detectable in up to 80 percent of patients [2]. Because there is no first-line therapy for NXG, its treatment is difficult, especially in elderly patients. We report a case of NXG on the extremities successfully treated with low-dose oral prednisolone.


Figure 1Figure 2
Figure 1.
1A) Diffuse infiltrate with amorphous necrobiotic areas in the dermis and subcutaneous tissue (H&E, x20)
1B) Numerous cholesterol clefts and the granulomatous cell infiltrate mainly composed of histiocytes and foamy multinucleated giant cells (H&E, x200).

Figure 2. Clinical findings before treatment.
2A) Lateral aspect of the left lower leg. Progressive yellow-brown plaque with central atrophy and extensive ulceration.
2B) Ulnar side of the left forearm. Indurated red plaque.
Clinical findings at 6 months after treatment.
2C) Lateral aspect of the left lower leg.
2D) Ulnar side of the left forearm.

A 93-year-old Japanese woman presented with a slightly painful plaque on her left leg. It had become obvious 6 months before and gradually expanded in size. She denied any previous trauma to the region. She had a history of pulmonary tuberculosis when she was 30 years old and had been successfully treated.

The clinical presentation revealed a localized yellowish plaque with surrounding reddish border on her left lower leg. There was no evidence of lymphadenopathy. Histological evaluation demonstrated hyaline necrobiosis and granulomatous foci within dermal and subcutaneous tissues (Figure 1A). The granulomatous area was composed of histiocytes, some of which had foamy cytoplasm, and multinucleated giant cells. There were also numerous cholesterol crystals in the center of degenerated collagen areas (Figure 1B). Evaluation of the cutaneous infiltrate contained mature CD38 positive plasma cells that stained for both κ and λ light chains. Investigations of microorganisms using Periodic acid-Sciff (PAS), Grocott, Ziehl-Neelsen stainings were negative.

Chest CT scan showed scar formation in the left superior lobe, whereas further investigations for pulmonary tuberculosis, including acid-fast bacterial fluorescent staining, culture, and polymerase chain reaction (PCR) examination of the skin lesion and the sputum, did not show evidence of tuberculosis. The tuberculin skin test was only weakly positive. Laboratory investigations revealed mild anemia (red blood cell count: 393x104 /μl, hemoglobin: 10.7 g/dl), decreased level of platelets (10.2x104 /μl), slightly elevated levels of C-reactive protein (0.43 mg/dl), and elevated erythrocyte sedimentation rate (48 mm/hr). Antinuclear antibodies were positive at a titer of 1:160 with a PCNA like pattern, although she had no other clinical or laboratory findings suggestive of autoimmune disorders. Urine electrophoresis for Bence-Jones protein was negative. Investigations of the serum protein fraction showed an elevated level of IgG (2305 mg/dl). Serum electrophoresis displayed the presence of an M-peak with IgG λ paraproteinemia. Further investigation with skull radiography, bone scintigraphy, and Gallium scintigraphy showed no evidence of systemic involvement.

Based on these results, she was diagnosed as having NXG. The patient initially declined further investigations including bone marrow examination and systemic treatment. Meanwhile, there was progressive ulcer formation in the biopsy region of the left leg. Six months later, multiple tender red dermal and subcutaneous nodules had gradually developed on her extremities (Figures 2A and 2B). Then, oral administration of prednisolone 20 mg daily (0.5 mg/kg) was started. After 4 weeks, she obtained resolution of the skin lesions and the serum IgG level decreased to a normal level although, IgG λ paraproteinemia have persisted. The prednisolone dose was gradually reduced to 7.5 mg daily without recurrence of the skin lesions for more than 6 months (Figures 2C and 2D).

There have been no definitive therapeutic guidelines for NXG because of its rarity. Because NXG is frequently complicated by paraproteinemia and 18 percent of patients have been reported to develop multiple myeloma [4], treatment of NXG is generally directed to the associated paraproteinemia. Treatment modalities include chlorambucil with or without corticosteroids, melphalan-corticosteroid combination, radiotherapy [4], cyclophospamide-dexamethasone combination [5], and intravenous immunoglobulin [6]. Surgical removal has been associated with a high rate of recurrence [4]. There have been two case reports in which NXG was successfully treated by high-dose oral dexamethasone [7, 8]; one of these patients had failed to respond to oral prednisolone 20mg daily for one week.

This is the first reported case in which NXG was successfully treated with low-dose prednisolone. Because paraproteinemia is more common in elderly patients [9], the incidence of NXG is predicted to increase in the near future. The treatment options should be tailored according to the patient’s age and co-morbidities. Especially for elderly patients, a gentle approach might be recommended. Although there are also significant side effects with medium-dose prednisolone in the long run, this might well be considered when other modalities are contraindicated.

References

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