Clinical Characteristics of Lupus Erythematosus Panniculitis/Profundus

Abstract

This case series characterizes the initial presentation and treatment of lupus erythematosus panniculitis/profundus and its association with systemic lupus erythematosus and discoid lupus erythematosus.

Lupus erythematosus panniculitis (LEP) is a rare variant of cutaneous lupus erythematosus characterized by tender, often painful, erythematous subcutaneous indurated nodules or plaques on fatty body areas.^1,2 Profound lipoatrophy often occurs, potentially leading to severe disfigurement. While LEP is frequently isolated, coexistence with discoid lupus erythematosus (DLE) (termed lupus profundus) or systemic lupus erythematosus (SLE) may occur.¹ Diagnosis is often delayed, increasing the risk for sequalae, such as atrophy and calcinosis.^3,4

Existing literature on LEP is limited to small case series,^2,3,5 leading to poorly defined clinical characteristics and treatment algorithms. Herein, we present a case series of 61 patients with confirmed LEP and characterize initial presentation, treatment, and association with SLE and DLE.

Methods

The study was approved by the Partners Healthcare and the New York University Grossman School of Medicine institutional review boards. Patient informed consent was waived owing to the use of deidentified data. This waiver of consent was approved by both institutional review boards. After institutional review board approval, we performed an International Classification of Diseases (ICD-9 and ICD-10) code and natural-language query for medical records from New York University Langone Health, Brigham and Women’s Hospital, and Massachusetts General Hospital to identify all cases of LEP diagnosed based on biopsy and/or expert opinion from January 2000 through October 2019. Of 5717 cutaneous lupus erythematosus medical records reviewed, we identified 61 LEP cases; 54 of 61 (88%) were biopsy confirmed.

Results

Of 61 patients, 52 (85%) were female; the mean age at symptom onset was 35.8 years (range, 2-67 years). Lupus erythematosus panniculitis involved 2 or more locations at presentation in 36 patients (59%), for a total of 105 distinct lesions. Common locations included proximal upper extremity (27.6%), face (17.1%), proximal lower extremity (14.3%), and back (10.5%). The majority presented with active erythematous palpable nodules/plaques (46 of 60 patients [77%]) and atrophy/contour change (38 of 60 patients [63%]) (Table 1).

Table 1. Patient Characteristics.

Characteristic	No. (%)
Age at symptom onset, mean (range), y	35.8 (2-67)
Sex
Female	52 of 61 (85)
Male	9 of 61 (15)
Race/ethnicity
White, non-Hispanic/Latino	24 of 56 (43)
African American/Black	13 of 56 (23)
Hispanic/Latino	10 of 56 (18)
Asian/Pacific Islander	9 of 56 (16)
Distribution of cutaneous lesions at presentation
Proximal upper extremity	29 of 105 (27.6)
Face	18 of 105 (17.1)
Proximal lower extremity	15 of 105 (14.3)
Back	11 of 105 (10.5)
Scalp	7 of 105 (6.7)
Chest	7 of 105 (6.7)
Buttock	6 of 105 (5.7)
Distal upper extremity	4 of 105 (3.8)
Abdomen	3 of 105 (2.9)
Distal lower extremity	2 of 105 (1.9)
Other: neck, ear, foot	3 of 105 (2.9)
No. of locations at presentation
Multiple (≥2)	36 of 61 (59)
Single	25 of 61 (41)
Lesion morphology at presentation
Active nodules/plaque	46 of 60 (77)
Areas of atrophy/contour change	38 of 60 (63)
Calcification	6 of 60 (10)
Ulceration	5 of 60 (8)
DLE	22 of 60 (37)
Active	14 of 22 (64)
Inactive	7 of 22 (32)
Unknown activity	1 of 22 (5)
Symptoms at presentation
Pain	36 of 58 (62)
Pruritus	15 of 55 (27)
Positive ANA at time of LEP diagnosis
All patients	44 of 59 (75)
SLE	9 of 9 (100)
DLE	11 of 16 (69)
SLE and DLE	7 of 7 (100)
Without SLE and/or DLE	17 of 27 (63)
Positive dsDNA antibody at time of LEP diagnosis
All patients	15 of 59 (25)
SLE	5 of 11 (46)
DLE	1 of 16 (6)
SLE and DLE	7 of 7 (100)
Without SLE and/or DLE	2 of 25 (8)
Mean time to diagnosis, mo
All patients (n = 45)	19.2
No history of SLE or DLE at presentation (n = 23)	29.8
History of SLE and/or DLE at presentation (n = 15)	8.8
Simultaneous onset/diagnosis
LEP and DLE (n = 6)	4.5
LEP and SLE (n = 1)	2.0

Abbreviations: ANA, antinuclear antibody; DLE, discoid lupus erythematosus; dsDNA, double-stranded DNA; LEP, lupus erythematosus panniculitis; SLE, systemic lupus erythematosus.

Overall, mean time from initial clinical presentation of LEP symptoms to diagnosis was 19.2 months (n = 45). For those without history of SLE or DLE at the time of LEP diagnosis, the mean time to diagnosis was 29.8 months, whereas for those with a history of SLE and/or DLE, it was 8.8 months.

Of the 61 patients, 21% had coexistent SLE, 28% had coexistent DLE, and 13% had both. Of those with SLE (n = 21), 17 were diagnosed with SLE prior to LEP onset, 3 developed SLE after LEP (mean, 10.1 and 8.7 years between diagnoses, respectively), and 1 was diagnosed simultaneously. Of patients with concomitant DLE (n = 24), 13 had DLE prior to LEP, 2 developed DLE after (mean, 10.0 and 2.1 years between diagnoses, respectively), and 9 were diagnosed simultaneously.

Overall, a mean of 2.5 systemic therapies were required for disease control (Table 2), and 30 of 58 patients (52%) required at least 1 immunosuppressive medication. The most commonly used therapies were hydroxychloroquine and methotrexate. Patients without coexistent DLE or SLE required a mean of 2.1 systemic therapies, whereas those with coexistent SLE and/or DLE required a mean of 2.8 systemic therapies for LEP control. Notably, 42% (13 of 31) of those with coexistent DLE and/or SLE were taking an immunosuppressant at LEP onset.

Table 2. Treatment Frequency.

Treatment	Coexistent SLE and/or DLE, No. (%)
	No (n = 21)	Yes (n = 37)
Hydroxychloroquine	17 (81)	27 (73)
Chloroquine	0	4 (11)
Quinacrine	2 (10)	5 (14)
Methotrexate	9 (43)	11 (30)
Mycophenolate mofetil	0	9 (24)
Azathioprine	1 (5)	8 (22)
Dapsone	5 (24)	5 (14)
Thalidomide	0	5 (14)
Leflunomide	0	2 (5)
Belimumab	0	4 (11)
IVIG	1 (5)	1 (3)
Rituximab	0	1 (3)
Adalimumab	1 (5)	0
Cyclosporine	0	1 (3)
Lenalidomide	0	1 (3)
Colchicine	1 (5)	0
Prednisone	9 (43)	18 (49)
Intralesional steroid	5 (24)	17 (46)
Autologous fat transplant/dermal filler	2 (10)	3 (8)
No. of systemic treatments, meana	2.1	2.8

Abbreviations: DLE, discoid lupus erythematosus; IVIG, intravenous immunoglobulin; SLE, systemic lupus erythematosus.

^aExcludes autologous fat transplant/dermal filler and intralesional steroid.

Discussion

In this large cohort of patients with LEP, LEP occurred predominantly in middle-aged women and commonly affected the proximal extremities, face, and back.^3,5 The majority of patients (62%) had coexistent LEP with SLE and/or DLE, most diagnosed with SLE or DLE prior to LEP.

We detected an overall mean diagnostic delay of 19.2 months; in patients without SLE or DLE, the delay was 29.8 months. This is notable given the atrophy and permanent contour change associated with LEP. Indeed, 68.7% presented with atrophy, suggesting an association of diagnostic delays with potentially preventable disfigurement.

The majority of patients required more than 2 systemic therapies, suggesting that LEP is often refractory to first-line therapy, typically hydroxychloroquine. Furthermore, those with coexistent SLE or DLE experienced more refractory disease; 42% were receiving immunosuppressive therapy at time of LEP diagnosis, suggesting that LEP in the setting of SLE or DLE is particularly recalcitrant to therapy.

Lupus erythematosus panniculitis is rare and difficult to diagnose, particularly in those without SLE or DLE at presentation. Our findings, which demonstrate diagnostic delay and refractory disease, underscore the need for earlier diagnosis and treatment to prevent pain and irreversible atrophy. Limitations of this study include its retrospective design and limited sample size, although to our knowledge this is one of the largest LEP cohorts described to date.