Digging deeper into lupus erythematosus panniculitis
By Warren Heymann, MD
May 5, 2021
Vol. 3, No. 18
Lupus erythematosus panniculitis (aka lupus erythematosus profundus, LEP) has a storied history. The famed clinician Harry Arnold noted that Kaposi (when he was Kohn) observed nodules in patients with lupus. (1) Debates and controversies ensued for decades, with many authorities thinking that these nodules were subcutaneous sarcoidosis. In 1940, Irgang described the case of a 23-year-old woman with histologic evidence of [what I interpret as] discoid lupus with subcutaneous involvement [that histologically fulfills modern criteria] and used the term “lupus erythematous profundus.” (2) The concept of LEP was solidified by Arnold 16 years later as he presented four additional cases, where he lamented over the term lupus erythematosus profundus:
The choice of the adjective profundus for the last-named category of cases was a somewhat unhappy one on two principal grounds: It does not clearly indicate that the lesions are clinically subcutaneous rather than merely “extending deeply” and it invites confusion with a quite different lesion, Brocq’s lupus érythémateux profond, which was either lupus vulgaris or else the same as Bechet’s lupus erythematosus hypertrophicus (et profundus). Lupus erythematosus subcutaneous might have been preferable. (1)
Most authors today use both terms for LEP (panniculitis or profundus) interchangeably (as I will in this commentary), although some authorities prefer to use the term profundus when lupus involves the epidermis, dermis, and adipose tissue, as in Irgang’s case.
LEP occurs in 1% to 3% of patients with cutaneous lupus erythematosus, mostly affecting females of childbearing age, with a female to male ratio of 4.5:1. (3) LEP presents as persistent, often painful subcutaneous nodules, ranging from 1 to 5 cm in diameter, mainly involving the proximal extremities (lateral aspects of the arms and shoulders), thighs, buttocks, trunk, face, and scalp. Overlying skin may appear erythematous. Lesions may ulcerate, healing with atrophy, skin depression, dimpling, and scarring. LEP may present as the sole manifestation of the disease or associated with discoid and/or systemic lupus. Although spontaneous resolution may occur, LEP may follow a chronic course of remission and exacerbation persisting for months to years. (4,5) Histologically, LEP variably displays a lymphoplasmacytic lobular panniculitis with epidermal and dermal changes of lupus, hyaline fat necrosis, and lymphoid follicles. Immunohistochemistry shows a mixture of T and B cells in the dermis and subcutaneous tissue, with a slight preponderance of T cells. Although the polymerase chain reaction analysis of the T-cell receptor-[gamma] gene rearrangement is polyclonal in most cases, a small portion of specimens demonstrate monoclonality. (6)
A major caveat in treating patients with LEP is being confidant that your patient does not have subcutaneous panniculitiis-like T-cell lymphoma (SPTCL). This is especially important in those cases that are unassociated with cutaneous or systemic lupus and/or have been recalcitrant to therapy. A recent example is that of a 45-year-old woman treated as LEP for two years with hydroxycholoroquine and topical corticosteroids; a biopsy was performed because of her disease progression, and she was diagnosed with a primary cutaneous gamma-delta T-cell lymphoma. Differentiating LEP from SPTCL may be extraordinarily difficult. LEP displays CD123 + plasmacytoid dendritic cells (7); Ki-67 “hot spots” and the presence of the MYC oncoprotein favor the diagnosis of SPTCL. (6)
The pain, scarring, and atrophy of LEP can be devastating physically and emotionally. Aggressive treatment is warranted; unfortunately, large randomized trials have not been performed, so evidence is based on case reports and small case series. Antimalarials and steroids (topical and intralesional) are considered first-line therapies. Where the literature gets muddled is in deciding what to do next should first-line treatments fail or are contraindicated. When you read a “typical” case report, there will be a litany of drugs that have been attempted unsuccessfully, until voila the reported drug worked. In the next article, the drug you just read about offered no benefit, but another one was beneficial. Each of the following have been recently reported to be of benefit: rituximab (8), tociluzumab (9), IVIG (5), in addition to our armamentarium of well-known therapies (methotrexate, mycophenolate mofetil, dapsone, and thalidomide). (10) Why a particular drug is beneficial in one patient with LEP but not another requires a greater comprehension of its pathophysiology.
Beyond the presumption that a complex interplay between innate and adaptive arms of the immune system in genetically predisposed patients is at play, the pathogenesis of LEP remains an enigma. (8). Clues are afforded by each of the mechanism of therapies utilized (e.g., What role does IL-6 play? How important is the JAK/STAT pathway? etc.) The only certainty of LEP is that it is a deep form of cutaneous lupus involving the subcutaneous tissue. It will be necessary for dermatologic investigators to dig deeper to understand its pathogenesis to develop optimal therapies.
Point to remember: Lupus erythematosus panniculitis must be differentiated from subcutaneous panniculitis-like T-cell lymphoma. While there have been recent reports of therapeutic success for LEP, further research is required to determine the optimal treatment for those cases that do not respond to antimalarial or steroid therapy.
Our expert’s viewpoint
Lisa Pappas-Taffer, MD
Assistant Professor of Clinical Dermatology
University of Pennsylvania
Connective tissue disease (CTD) panniculitides can occur in the setting of patients with a clear diagnosis of lupus, dermatomyositis, systemic sclerosis or morphea, but they can also occur as an isolated entity. All of them have predominantly lobular lymphocytic infiltrates, but the pathology is not always straightforward. Sometimes they have additional septal involvement and sometimes there can be overlapping CTD features making the diagnosis more challenging.
In my practice, I always biopsy presumed CTD panniculitides to rule out a lymphoproliferative or infectious panniculitis. I find lupus profundus (discoid lupus overlying panniculitis, LP) and lupus erythematosus panniculitis (LEP) to be quite treatment responsive compared with the other CTD panniculitides, with many patients achieving a maintained remission on antimalarial therapy alone. The use of oral steroids is typically not recommended for cutaneous lupus. However, many of my LP/LEP patients are young women with lateral face involvement, so I use prednisone to bridge the antimalarial’s delayed efficacy — the goal being to reduce inflammation quickly and minimize the resultant facial atrophy. My typical regimen includes a 1-2-month prednisone taper (0.75- 1 mg/kg/day) starting at the time of hydroxychloroquine (<5 mg/kg/day) or chloroquine (<2.3 mg/kg/day) initiation. For the small percentage of patients who fail this regimen, the patient and I together pick the steroid-sparing agent that best suits the patient’s comorbidity profile, desire to drink alcohol, cost, and personal preference, as no second-line agent has been deemed better than another.
The psychological impact of LP/LEP, especially on the face, is important to address. I typically discuss treatment as a two-pronged approach — 1) attacking the inflammation to minimize the resultant atrophy, and 2) treating the resultant atrophy, if desired, once maintained disease control is attained. The use of cosmetic fillers (hyaluronic acid, poly L-lactic acid, or autologous fat transfer) for LP/LEP-induced facial atrophy can be life changing for patients. Some dermatologists advocate waiting two years from disease control prior to considering cosmetic filler injection to minimize the risk of disease reactivation as a result of antigenic stimulation. However, 2 years is an arbitrary duration of time, and there have been no reported cases (to my knowledge) of reactivation of CTD following the injection of inert cosmetic fillers. Instead, there are a few case reports demonstrating no reactivation at 1 year following hyaluronic acid and poly L-lactic acid in patients with quiescent LEP for several years prior to injections (11) , and no reactivation at 1 and 3 years following autologous fat transfer in 2 patients with quiescent disease for over a year prior to injections. (12) Although I still discuss the theoretical risk for reactivation due to the filler (per above), I instead emphasize that independent recurrence of the LP/LEP post-filler could make assessment of activity and treatment response potentially more challenging, but not impossible.
Arnold HL. Lupus erythematosus profundus: Commentary and report of four more cases. Arch Dermatol 1956; 73(1):15-33.
Irgang S. Lupus erythematosus profundus: Report of an example with clinical resemblance to Darier-Roussy sarcoid. Arch Dermatol Syphilol 1940; 42: 97-108.
Schwartz Z, Magro CM. Intralesional overlap syndrome: Sclerodermic lupus panniculitis and sclerodermic discoid lupus erythematosus. JAAD Case Rep 2020; 6: 166-168.
Kimball H, Kimball D, Siroy A, Tuna IS, et al. Novel diagnostic imaging features of facial lupus panniculitis: Ultrasound, CT, and MR imaging with histopathology correlate. Clin Imaging 2019; 58: 177-181.
AlQadri N, AlNooh B. AlTewerki MM, Almotairi A, Alajlan S. Intravenous immunoglobulin in the management of lupus erythematosus panniculitis. Cureus 2020; 12: e6790.
Heymann WR. The challenge of identifying identical twins: Advances in differentiating lupus erythematosus panniculitis from subcutaneous panniculitis-like T cell lymphoma. Skinmed 2019; 17: 115-116.
von Dücker L, Fleishcer M, Stutz N, Thieme M, et al. Primary cutaneous gamma-delta T-cell lymphoma with long-term indolent clinical course initially mimicking lupus erythematosus profundus. Front Oncol 2020 Feb 19;10:133. doi: 10.3389/fonc.2020.00133.
Correll CK, Miller DD, Maguiness SM. Treatment of childhood-onset lupus erythematosus panniculitis with rituximab. JAMA Dermatol 2020; 156: 566-569.
Elolemy G, Al Rashidi A, Dehrab A, Almathkouri A, et al. Successful treatment of refractory lupus erythematosus profundus with the interleukin-6 antagonist tocilizumab: A case report. Lupus 2020 Mar 19:961203320913944. doi: 10.1177/0961203320913944. [Epub ahead of print]
Vaidya B. Baral R, Baral H, Nakarmi S. Sustained drug free remission of lupus panniculitis with methotrexate: A case report from Nepal. JNMA J Nepal Med Assoc 2018; 56(214): 963-966.
Eastham AB, Liang CA, Femia AN, Lee TC, Vleugels RA, Merola JF. Lupus Erythematosus Panniculitis-induced Facial Atrophy: Effective Treatment With Poly-L-Lactic Acid and Hyaluronic Acid Dermal Fillers. J Am Acad Dermato. Nov 2013;69(5):e260-e262.
Polivka L, Revol M, Battistella M, Bachelez H. Lipofilling: A New Therapeutic Option for the Treatment of Lupus Panniculitis-Induced Atrophy. Case Rep Dermatol. Sep-Dec 2016;8(3): 323-326.
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