Tumid Lupus Erythematosus

Article Author:
Dahlia Saleh
Article Editor:
Jonathan Crane
Updated:
9/12/2019 8:12:49 AM
PubMed Link:
Tumid Lupus Erythematosus

Introduction

Cutaneous lupus erythematosus (CLE) can present in three forms: acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), and chronic cutaneous lupus erythematosus (CCLE). CCLE can be further be subdivided into chronic subtypes consisting of tumid lupus erythematosus (TLE), discoid lupus erythematosus (DLE), chilblain lupus erythematosus, and lupus erythematosus panniculitis. Although these forms possess morphologies and histological features distinct from one another, more than one form can co-occur in the same patient.[1][2][3]

Although tumid lupus erythematosus (TLE) is currently considered to be a subtype of cutaneous lupus erythematosus (CLE), TLE differs from the other subtypes of cutaneous lupus erythematosus in that an association with systemic lupus erythematosus (SLE) is rare. Because of this weak association with SLE and a relative lack of serologic abnormalities in patients with TLE, some consider TLE to be an entity separate from lupus. It has also been postulated that TLE is on a clinical gradient with lymphocytic infiltrate of Jessner and reticular erythematous mucinosis (REM) due to similar findings on histology.

Tumid lupus erythematosus (TLE) typically presents as annular, indurated, erythematous, edematous plaques without epidermal involvement. If any of these features are recognized, epidermal involvement is likely, and a diagnosis of DLE should be suspected. Typical locations of TLE are the face and trunk, and lesions respond well to photoprotection, topical corticosteroids, and antimalarials.

Etiology

To date, no distinct etiology for TLE has been identified. However, triggering factors such as ultraviolet (UV) radiation have been implicated in worsening lesions of TLE. Its association with autoimmune disease has been controversial; if an autoimmune disease is suspected, an autoimmune workup may be initiated.[4][5]

Epidemiology

CCLE, in general, occurs more frequently in the female population. TLE is rare relative to DLE; DLE is responsible for the majority of CCLE cases and is more frequent in the African American population. The epidemiology of tumid lupus specifically has not been well studied.

Pathophysiology

Cutaneous lupus has a complex pathogenesis that relies on the interplay between genetic and environmental components. For all types of CCLE, including tumid lupus, UV radiation (specifically UVB) serves as a trigger. Immune alterations have also been implicated in the pathogenesis of TLE, specifically upregulation of T-regulatory cells, decreased epidermal Langerhans cells, increased plasmacytoid dendritic cells, upregulated type-1 interferon, tumor necrosis factor-alpha (TNF-alpha), and Th17 cells. It has also been postulated that tobacco smoking is a risk factor for TLE. It has also been suggested that rare drug-induced forms of TLE exist in association with TNF-alpha inhibitors, thiazide diuretics, highly active antiretroviral therapy (HAART), and angiotensin-converting enzyme (ACE) inhibitor, bortezomib, and ustekinumab therapy.

Histopathology

TLE has abundant dermal mucin deposition and a superficial and deep perivascular and periadnexal infiltrate, typically involving the eccrine coil. There is no epidermal change or follicular plugging as seen in discoid lupus erythematosus. It is important to note that a separate clinical entity, reticular erythematous mucinosis (REM), is indistinguishable histologically from tumid lupus.

History and Physical

History is a valuable tool in evaluating a patient for TLE. Worsening of the eruption with sun exposure supports a diagnosis of TLE, although this finding is not specific to TLE. A full body skin exam should be performed when a diagnosis of TLE is suspected. TLE favors the face, neck, chest, and back, so special attention should be given to these body regions. Lesions present as edematous, usually annular, plaques with hues ranging from erythematous to violaceous. Epidermal change virtually excludes a diagnosis of TLE (TLE lesions lack atrophy, ulceration, follicular plugging, scarring, or dyspigmentation, and the presence of these features favors a diagnosis of DLE). Although uncommon, TLE may present with a Blaschkoid distribution, periorbital edema, or scalp involvement that appears similar to alopecia areata.

Lesions of TLE persist for days or weeks and chronically recur. Lesions do have the potential to regress spontaneously; however, patients may report recurrence during the summer months.

Evaluation

If the clinical examination is consistent with cutaneous lupus, a lesional biopsy should be taken from an active, erythematous plaque. A punch biopsy (4 mm is recommended on the trunk or 3 mm on cosmetically sensitive areas such as the face) should be performed to include the full thickness of the dermis. As discussed above, the classic histopathologic findings are abundant interstitial mucin and a dermal perivascular and periadnexal lymphocytic infiltrate.[6][7][8]

If the histopathologic findings definitively support a diagnosis of tumid lupus, the patient should be evaluated for systemic disease, despite the weak association with SLE. The evaluation for systemic lupus includes a full history and review of systems, physical examination with special attention taken to lymphadenopathy or arthritis, and laboratory tests (ANA with anti-dsDNA and anti-Sm profiles), urinalysis, complete blood count (CBC) with differential, chemistries, ESR, CRP, complement levels (C3, C4), and antiphospholipid antibodies. For a more extensive autoimmune workup, autoantibodies such as SS-A/Ro and SS-B/La, anti-U1RNP, and anti-histone antibody can be drawn.

If the histology is consistent with lupus but not definitive, a lesional biopsy can be sent for direct immunofluorescence (DIF). The most characteristic DIF finding in cutaneous LE is granular IgG and/or IgM deposition at the dermal-epidermal junction and around hair follicles. However, with tumid lupus specifically, DIF is often negative or nonspecific and therefore may not be as valuable as in other forms of cutaneous lupus.

Phototesting can be beneficial for diagnosing TLE; reproduction of lesions after UVA/UVB irradiation may support a diagnosis of tumid lupus.

Treatment / Management

Photoprotection and topical or intralesional corticosteroids are first-line therapy for localized TLE. Particularly in active TLE lesions, intralesional triamcinolone (4 to 5 mg/mL) is often effective. Topical calcineurin inhibitors (e.g., tacrolimus), are also effective.[9]

Patients with limited TLE that is refractory to topical therapy and patients with extensive TLE should be treated with antimalarial therapy (first-line). Hydroxychloroquine or chloroquine can be used initially. Between 200 and 400 mg per day of hydroxychloroquine is a reasonable dose. For chloroquine, a dose of 125 to 250 mg per day (for 5 to 7 days per week) is commonly used. Hydroxychloroquine and chloroquine may not be used in combination due to the risk of retinal toxicity. Their risk of retinal toxicity limits the maximal dose of these antimalarials. It is important to note that it may take 8 to 12 weeks to appreciate the effects of antimalarials. It is important for patients to be aware of the skin depigmentation that can occur with both hydroxychloroquine and chloroquine. This presents as a blue-gray discoloration on the shins, palate, nails, or face, and this discoloration may be permanent. Gastrointestinal side effects are the most common reason for discontinuation of antimalarial treatment.

TLE refractory to antimalarial therapy is rare. However second-line therapy includes methotrexate (7.5 to 25 mg once weekly) or mycophenolate mofetil (1 to 3 gm per day). Folic acid 1 mg per day typically lessens the severity of the side effects associated with methotrexate. Side effects of methotrexate include gastrointestinal upset, pulmonary fibrosis, bone marrow suppression, and alopecia. Mycophenolate mofetil’s side effects include gastrointestinal upset, reversible cytopenias, immunosuppression, gastrointestinal perforation or ulcer, hypercholesterolemia, and hypertension.

Third line treatment options, although uncommonly used, include thalidomide and lenalidomide.

Differential Diagnosis

The differential diagnoses of tumid lupus include lymphocytic infiltrate of Jessner, polymorphous light eruption, cutaneous lymphoid hyperplasia (pseudolymphoma of the skin), and reticular erythematous mucinosis.

Enhancing Healthcare Team Outcomes

SLE is a systemic disorder managed by an interdisciplinary team. The disorder has no cure and is chronic and progressive. Another subtype of chronic SLE is TLE.  Although tumid lupus erythematosus (TLE) is currently considered to be a subtype of cutaneous lupus erythematosus (CLE), TLE differs from the other subtypes of cutaneous lupus erythematosus in that an association with systemic lupus erythematosus (SLE) is rare. Because of this weak association with SLE and a relative lack of serologic abnormalities in patients with TLE, some consider TLE to be an entity separate from lupus. The disorder is best managed by a dermatologist and/or rheumatologist but the patient can be followed by the primary care provider and nurse practitioner with the assistance of a specialty trained dermatology nurse. The nurse should assist with the coordination of follow-up, patient and family education, and monitoring for untoward changes reporting concerns to the team. A pharmacist should assist in management of the medications required for treatment. Evaluating for potential drug-drug interactions, providing patient education, and reporting to the team if any problematic events develop in regard to the pharmaceutical therapy. By working as an interprofessional team, the best outcomes can be achieved.

Tumid lupus erythematosus (TLE) typically presents as annular, indurated, erythematous, edematous plaques without epidermal involvement. If any of these features are recognized, epidermal involvement is likely, and a diagnosis of DLE should be suspected. Typical locations of TLE are the face and trunk, and lesions respond well to photoprotection, topical corticosteroids, and antimalarials.


References

[1] Concha JSS,Werth VP, Alopecias in lupus erythematosus. Lupus science     [PubMed PMID: 30397497]
[2] Abadías-Granado I,Sánchez-Bernal J,Felipo-Berlanga F,Ara-Martín M, Coexistence of Tumid Lupus Erythematosus and Discoid Lupus Erythematosus. Actas dermo-sifiliograficas. 2018 Jul 30;     [PubMed PMID: 30072022]
[3] Powell R,Hile G,Lowe L,Kahlenberg JM, Herpes zoster infection after topical steroid use in the setting of tumid lupus erythematosus. JAAD case reports. 2018 Jan;     [PubMed PMID: 29379863]
[4] Jefferson GD,Aakalu VK,Braniecki M, Tumid lupus: An unexpected diagnosis for the otolaryngologist. American journal of otolaryngology. 2017 Mar - Apr;     [PubMed PMID: 28122678]
[5] Fogagnolo L,Soares TC,Senna CG,Souza EM,Blotta MH,Cintra ML, Cytotoxic granules in distinct subsets of cutaneous lupus erythematosus. Clinical and experimental dermatology. 2014 Oct;     [PubMed PMID: 25214407]
[6] Verma P,Sharma S,Yadav P,Namdeo C,Mahajan G, Tumid lupus erythematosus: an intriguing dermatopathological connotation treated successfully with topical tacrolimus and hydroxyxhloroquine combination. Indian journal of dermatology. 2014 Mar;     [PubMed PMID: 24700961]
[7] Bajaj DR,Devrajani BR,Matlani BL, Discoid lupus erythematosus: a profile. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2010 Jun;     [PubMed PMID: 20642962]
[8] Goerig R,Vogeler C,Keller M, Atypical presentation of cutaneous lupus mucinosis. The Journal of clinical and aesthetic dermatology. 2013 Apr;     [PubMed PMID: 23630641]
[9] Abdullah L,Abbas O, Dermacase: Can you identify this condition? Tumid lupus erythematosus. Canadian family physician Medecin de famille canadien. 2012 Jul;     [PubMed PMID: 22798463]