Papulonodular mucinosis associated lupus erythematosus: A case series and a literature review

Papulonodular mucinosis (PNM) is a rare cutaneous manifestation of lupus erythematosus (LE), often classified as a dermal subtype of cutaneous lupus erythematosus (CLE). Clinically described as flesh-coloured papulonodules, it is characterized histologically by abundant dermal mucin deposition with scarce or absent inflammatory infiltrate.1-3 Characteristics and prognosis of PNM remain poorly known. We conducted a retrospective case series of seven patients diagnosed with LE and PNM, followed in two French dermatology departments between 1999 and 2024. Systemic lupus erythematosus (SLE) was classified according to ACR/EULAR 2019 criterias4 and disease severity according to revised EULAR 2023 recommendations (Severe disease: major organ threatening disease; thrombocytopenia with platelets 12; ≥1 BILAG A manifestations…).5 PNM diagnosis was assessed on clinicopathologic correlation: skin-coloured papulonodules with rich dermal mucin deposits and sparse inflammatory infiltrates. Tumid lupus, reticulated erythematous mucinoses and Jessner's lymphocytic infiltrates were excluded based on the absence of erythema, reticulated or arciform arrangement, nor photosensitivity, had a scarring evolution and showed very poor to no dermal lymphocytic infiltrate. Patient characteristics are summarized in Table 1. All seven patients had SLE, which preceded PNM in four cases (by 2 to 37 years). Lesions consisted of confluent flesh-coloured papulonodules forming plaques or tumours, evolving into dyschromic and anetodermic scars (n = 4) or scarring alopecia (n = 2) (Figure 1a–e). Histology consistently revealed abundant dermal mucin deposition between collagen bundles with little or no interface dermatitis or periadnexal/perivascular infiltrate (Figure 1f,g). All patients had associated classical CLE subtypes including discoid lupus erythematosus (DLE) in all seven and lupus panniculitis in one. Four patients (57%) had nephritis and five (71%) had joint involvement. Severe systemic manifestations occurred in four patients (57%), including haemophagocytic lymphohistiocytosis, cerebral vasculitis with meningitis, immune thrombocytopenia, pneumonitis and retinal vasculitis. DLE Arthritis GN (class III + V) HLH DLE Arthritis GN (class II + V) Cerebral vasculitis Lymphocytic meningitis DLE Lupus panniculitis GN (class V) ITP DLE GN (class IV + V) DLE Arthritis DLE Arthritis Organized pneumonia Retinal vasculitis Chorioretinopathy Sjogren syndrome DLE Arthritis HCQ SC (1 mg/kg/day) CYC HCQ SC (1 mg/kg/day) MMF CYC HCQ SC (1 mg/kg/d) HCQ SC (1 mg/kg/day) MMF HCQ SC (1 mg/kg/day) MTX (15 mg/w) Thalidomide HCQ SC (1 mg/kg/d) MTX (15 mg/w) HCQ SC (0.25 mg/kg/day) MTX (15 mg/w) All patients had positive antinuclear antibodies, six (85%) had anti-dsDNA, six anti-U1RNP, five (71%) anti-Sm and three (42%) anti-Ro/SSA antibodies. All were treated with hydroxychloroquine and systemic corticosteroids (main dose of 1 mg/kg/day) with three receiving low-dose methotrexate, two cyclophosphamide and two mycophenolate mofetil. The historical median peak SLEDAI was 13 (range 8–40). Two patients experienced a moderate flare while five had a severe flare (71%)5 with PNM onset coinciding with flares in six cases. Although complete or partial PNM remission was achieved in all patients with standard lupus therapies, several developed severe systemic complications years after SLE diagnosis, but shortly after PNM onset. A systematic literature review identified 61 patients with PNM, reported in 49 English-language articles published between 1954 and 2024 (PubMed and MEDLINE). The median age was 37 years, and 45% were male (Table 1). Lupus history preceded PNM in 40% of cases and diagnosis was concomitant in 52% of cases. PNM was more frequently associated with SLE (82%) than classical CLE (40%) or DLE (10%–40%).6, 7 Extra-cutaneous involvements primarily included arthritis (38%), nephritis (36%) and haematological manifestations (20%).3, 8-10 Overall lupus severity could not be reliably assessed across many publications, and several authors report no clear evidence linking PNM to severe organ involvement nor heightened disease activity.2 However, our case series suggests a potential association between PNM and severe SLE flares even though a recruitment bias from tertiary centres cannot be excluded. Because PNM may precede or coincide with severe SLE flares, early recognition is crucial. Differentiation from other mucinous lupus variants, such as tumid lupus, can be challenging. Key diagnostic features include the absence of photosensitivity, flesh-coloured tumoural lesions with scarring evolution, antibody positivity, abundant mucin deposition without inflammatory infiltrates and SLE association. In conclusion, PNM represents a rare but meaningful cutaneous marker of SLE warranting systematic lupus serology and close monitoring for severe systemic involvement. The authors have nothing to report. All authors report no disclosure related to this work. Dr. Jachiet was a speaker for AstraZeneca and GSK outside the submitted work. J-D. Bouaziz was a medical advisor and speaker for AstraZeneca and GSK. Dr. Chasset has received grant/research support from AstraZeneca, BMS and GSK outside the submitted work; participated in an advisory board related to lupus for AstraZeneca, Biogen, GSK, Celgene, Merck, Horizon Therapeutics, Novartis, Kyowa Kirin and Principabio; and received speaking fees and honoraria from AstraZeneca and GSK BMS related to lupus. Dr. Cassius received speaking and consulting fees from Almirall SAS, AstraZeneca, AbbVie, BMS, Janssen-Cilag, Leo Pharma, Lilly France SAS, Novartis Pharma SAS, Sanofi Aventis France outside the submitted work. Dr. Battistella reported personal fees from Innate Pharma, Kyowa Kirin, Recordati Rare Diseases, Bristol Myers Squibb, Merck Sharpe & Dohme and Regeneron outside the submitted work. Dr. Mahévas was a speaker for Johnson and Johnson, Sanofi, Sobi, Almirall, Novartis, AbbVie. No other disclosures were reported. This study was conducted in compliance with the Good Clinical Practice protocol and the Declaration of Helsinki principles. The study was approved by the local ethics committee. The patients in this manuscript have given written informed consent to the publication of their case details. The data that support the findings of this study are available from the corresponding author upon reasonable request.