General Dermatology

Use of MxA Immunohistochemistry for Distinguishing Chilblain Lupus Erythematosus Skin Lesions From Idiopathic Chilblains, Perniosis

Chilblain lupus erythematosus (CHLE) is a rare form of cutaneous lupus erythematosus that presents with distinct painful lesions on acral surfaces. CHLE lesions mimic idiopathic chilblains and idiopathic perniosis lesions both clinically and histologically.¹ ² ³ ⁴ Because ≥ 18% of patients with CHLE progress to systemic lupus erythematosus (SLE)1, it is important to distinguish it from idiopathic chilblains/perniosis.

Myxovirus resistance protein A (MxA) has recently been identified to stain interferon (IFN)-induced immune cells, which are implicated in the pathogenesis of CHLE.⁵ ⁶

Thirty-one skin biopsies were identified from pathology archives, and patient charts were reviewed to confirm diagnosis of CHLE or idiopathic perniosis (IP). Paraffin-embedded sections were stained with anti-MxA antibodies (clone M143; Millipore Sigma-Aldrich; St. Louis, MO) at a 1:400 dilution; histologic patterns were objectively characterized using a standardized form.

CHLE lesion biopsies were more likely to stain as diffuse sheets of cells with intense pigmentation and to involve > 50% of dermal infiltrate. These findings were identified more frequently in the CHLE group compared with the IP group, as evidenced by the large odds ratios and P value of < 0.005.

Use of MxA Immunohistochemistry for Distinguishing Chilblain Lupus Erythematosus Skin Lesions From Idiopathic Chilblains, Perniosis


MxA staining patternCHLE N = 11 (%)IP N = 20 (%)ORP-value
Intense8 (73)1 (5)50.66670.0014
Dermal infiltrate, >5010 (91)4 (20)400.0019
Individual cells8 (73)18 (90)0.29630.227
Small groups, 2 - 5 cells10 (91)16 (80)2.50.4407
Clusters, 6 - 10 cells9 (82)14 (70)1.92860.476
Diffuse sheets, > 11 cells9 (82)3 (15)25.50.0012
Dermal interstitium, superficial9 (82)13 (65)2.42310.3316
Dermal interstitium, deep8 (73)11 (55)2.18180.337
Within dermal endothelial wall cells1 (9)8 (40)0.150.0972
Within eccrine glands1 (9)7 (35)0.18570.1428
Periadnexal, perieccrine7 (64)11 (55)1.43180.6417
Periadnexal, follicular1 (9)2 (10)0.90.9347
Perivascular, superficial9 (82)16 (80)1.1250.9025
Perivascular, deep10 (91)16 (80)2.50.4407
Intraepidermal11 (100)18 (90)3.10810.4768
Basement membrane zone0 (0)0 (0)--

CHLE = chilblain lupus erythematosis; IP = idiopathic perniosis; MxA = myxovirus resistance virus protein A; OR = odds ratio

CHLE and IP have been historically difficult to distinguish based on histology alone. Our results suggest that MxA staining produces a unique pattern that may help identify patients with CHLE and its systemic manifestations, and distinguish them from isolated IP.

  1. Hedrich CM, Fiebig B, Hauck FH, Sallmann S, Hahn G, Pfeiffer C, Heubner G, Gahr M. Chilblain lupus erythematosus—a review of literature. Clin Rheumatol. 2008;27(8): 949-954.
  2. Singh S, Taneja N, Bala P, Verma KK, Devarajan LSJ. Aicardi‐Goutières syndrome: cold‐induced acral blemish is not always cryoglobulinaemic vasculitis or chilblain lupus. Clin Exp Dermatol. 2018;43(4): 488-490.
  3. Wang ML, Chan MP. Comparative analysis of chilblain lupus erythematosus and idiopathic perniosis: Histopathologic features and immunohistochemistry for CD123 and CD30. Am J Dermatol. 2018;0(4): 265-271.