Treatment of Childhood-Onset Lupus Erythematosus Panniculitis With Rituximab.

Importance: Childhood-onset lupus erythematosus panniculitis (LEP) is a rare and chronic disfiguring disease. A paucity of literature exists on the clinical manifestations of this disease and how best to treat it. Objectives: To describe the clinical features of childhood-onset LEP and report on the use of rituximab in treatment-refractory childhood-onset LEP. Design, Setting, and Participants: A retrospective, observational case series study was conducted of 4 patients with childhood-onset LEP who presented to a single-center, tertiary care clinic with pediatric dermatology and pediatric rheumatology clinics between July 1, 2014, and July 1, 2018, and were treated with rituximab. A literature review was conducted of the clinical features and treatment of childhood-onset LEP. Exposure: Rituximab therapy for childhood-onset LEP. Main Outcomes and Measures: Reduction in the number and size of erythematous and tender subcutaneous nodules (both visually and by palpation), reduction of facial atrophy (documented with serial photography), and tolerability of rituximab at 2 to 22 months after initiation of therapy. Results: Four patients (3 male; mean [SD] age at treatment, 15 [5.9] years) with refractory childhood-onset LEP were successfully treated with rituximab. All patients had a rapid and sustained response to therapy with rituximab. One patient (25%) had minor infusion reactions; otherwise, treatment was well tolerated. Conclusions and Relevance: This case series suggests that rituximab may hold promise as a treatment for refractory, childhood-onset LEP. Larger, prospective studies are needed to validate these findings; however, given the rarity of disease, large studies may be difficult to conduct.

Connective tissue panniculitis: lupus panniculitis, dermatomyositis, morphea/scleroderma.

Panniculitis is an uncommon cutaneous manifestation of connective tissue diseases. Our discussion will include panniculitis occurring in the setting of lupus erythematosus, dermatomyositis, and scleroderma/morphea. These subtypes of panniculitis are unified by an active inflammatory stage of the disease that can progress to develop scarring, atrophy, and calcifications. Treatment is most effective if initiated during the active phase of the disease and often requires systemic therapy because of the location of the inflammation. Antimalarials are the initial treatment of choice for most cases of lupus erythematosus panniculitis, whereas corticosteroids in combination with other steroid-sparing immunosuppressive agents are the first-line treatment for panniculitis in patients with dermatomyositis. The appropriate treatment for panniculitis in the setting of morphea/scleroderma varies based on clinical severity.

Intravenous immunoglobulin in lupus panniculitis.

Systemic lupus erythematosus (SLE) is a disease of unknown cause that may involve one or many organ or systems. Skin involvement is a major feature in this disease, and a wide variety of skin conditions may be present. Lupus erythematosus panniculitis (LEP) constitutes a rare form of cutaneous lupus characterized by recurrent nodular or plaque lesions that can vary from a benign and mild course to a more disfiguring disease. Initial therapy includes corticosteroids, antimalarials, and azathioprine and, in refractory cases, two antimalarials in association, mycophenolate mofetil, or other immunomodulators. Intravenous immuglobulin (IVIG) is used in many autoimmune disorders, like in SLE, although clinical trials have not yet taken place. In this report, we review skin manifestations of SLE and their treatment, IVIG, and finally a case of LEP successfully treated with IVIG when other therapy modalities failed.

Clinical entity of Lupus erythematosus panniculitis/lupus erythematosus profundus.

We reviewed the clinical and histological characteristics of the 44 cases of lupus erythematosus profundus (LEP) that have been encountered in our department. The female to male ratio was 4.5:1. The mean age of the females was 36 years, and the mean age of the males was 34 years. The most common sites were the face (38.4%) and upper limbs (26.0%). Even among the patients with LEP alone many of the positive patients had low antibody titers of 1:40 or 1:80. In 18 of the 44 cases SLE was complicated by LEP, and in those cases there was a tendency for LEP to develop during the course of SLE (11 cases). The important histological findings were lobular panniculitis associated with mucin deposition (32 cases) and a tendency to be associated with damage to the basal cell layer. In addition, the direct immunofluorescence test was positive in both the basement membrane (90.5%) and blood vessels (85.7%) in a high percentage of even the cases of LEP alone. Based on the above findings, LEP is a cutaneous variant of erythematosus, and the importance of the histological findings when making the diagnosis of LEP was reconfirmed.

Lupus erythematosus profundus (lupus panniculitis) induced by interferon-beta in a multiple sclerosis patient.

We report a patient with multiple sclerosis (MS) who developed subcutaneous nodules on the face, shoulders and extremities while being treated with interferon (IFN)-beta-1b. These nodules fluctuated in parallel with myelopathy, and were diagnosed as lupus erythematosus profundus (LEP) based on histopathological findings. The patient showed no relapse of either neurological symptoms or subcutaneous nodules after cessation of IFN-beta-1b. This agent can cause induration and necrosis in the sites of injection but also systemic skin lesions such as LEP ascribable to its immunomodulatory effects.

CXCR3-mediated recruitment of cytotoxic lymphocytes in lupus erythematosus profundus.

BACKGROUND: Lupus erythematosus profundus (LEP) is a rare variant lupus erythematosus with unclear etiology characterized by lobular panniculitis. Recently, we observed a case of LEP involving the lower right eyelid. Our immunohistological analyses of lesional skin biopsies revealed a type I IFN signature in the context of cytotoxic lobular panniculitis. OBJECTIVE: Since type I IFNs have been shown to be involved in other cutaneous LE subtypes, especially in chronic discoid LE, we hypothesized that a type I IFN driven immune response might play an important role in the pathogenesis of LEP. METHODS: In addition to the above case, 9 skin biopsies taken from 5 patients with LEP were analyzed for a type I interferon signature by immunohistochemistry. Furthermore, 8 skin biopsies taken from patients with active chronic discoid LE and 5 biopsies of healthy skin were included for control purposes. The inflammatory infiltrate was characterized using monoclonal antibodies specific for CD3, CD4, CD8, CD20, CD68, and CD123. Subsequently, we analyzed the expression the type I IFN Marker MxA, the cytotoxic molecules granzyme B and Tia1, the chemokine receptor CXCR3 and its ligand, the interferon inducible protein IP10/CXCL10. RESULTS: LEP skin lesions were characterized by a lobular panniculitis, dominated by cytotoxic CXCR3(+) lymphocytes. Strong MxA expression indicated extensive type I IFN production within the fat lobules. Numerous plasmacytoid dendritic cells appear to be the major source of type I IFNs. Lesional expression of IP10 links the type I IFN production and recruitment of CXCR3(+) lymphocytes. LIMITATIONS: The study was based on histological and immunohistological analyses in a limited number of patients, due to the rareness of the investigated disease. CONCLUSION: Our results demonstrate a type I IFN driven immune response in active LEP skin lesions. We suggest that this type I IFN driven inflammation is responsible for the recruitment of CXCR3(+) lymphocytes into fat lobules and enhance their cytotoxic capacity.

Maintaining remission of lupus erythematosus profundus (LEP) with cyclosporin A.

We report a young female patient with recurrent lupus erythematosus profundus (LEP) who has successfully maintained remission of LEP with cyclosporin A (CsA), although conventional treatments such as systemic corticosteroids (low-dose), dapsone, and other immunosuppressive drugs (azathiopurine, cyclophosphamide) could not maintain remission.

Lupus panniculitis: clinical perspectives from a case series.

OBJECTIVE: To review clinical and laboratory features of lupus panniculitis from a large group of patients. METHODS: Retrospective chart review of patients diagnosed with lupus panniculitis at a tertiary medical center from 1976 to 1993. RESULTS: Lupus panniculitis occurred most frequently in adult women. Skin lesions involved proximal extremities, trunk, face, and scalp. Only 4 of 40 patients fulfilled criteria for systemic lupus erythematosus (SLE), and, other than positive antinuclear antibodies, a paucity of other autoantibodies was seen. Average disease duration was 6 years (range 0-38). Treatment with antimalarial agents was undertaken in most cases. Disease related morbidity (disfigurement and disability) was relatively common, but death was rare. CONCLUSION: Lupus panniculitis is a chronic inflammatory disease of subcutaneous adipose tissue that can develop during the course of SLE, although most patients do not develop systemic lupus.

Panniculitis: recent developments and observations.

Dermatopathologists rarely greet a biopsy of panniculitis with total confidence that a specific, definitive diagnosis will be rendered. As with many other areas in dermatopathology, our understanding of the pathogenesis of many forms of panniculitis is incomplete. This article examines a subset of panniculitis primarily from a pathogenetic standpoint, with the intention of providing a differential diagnosis for those cases in which ischemic changes are seen in the subcutis. The diverse group of conditions evoked by this approach also shares the distinction of having been the focus of nosologic and causative controversy, both historically and currently. In particular, stasis-associated sclerosing panniculitis, vascular calcification-cutaneous necrosis syndrome (calciphylaxis), oxalosis, and nodular vasculitis-erythema induratum are examined in depth. Erythema nodosum and variants, other granulomatous panniculitides, and panniculitides showing cytophagocytosis are also discussed with current perspectives.

Lupus eritematoso sistémico de inicio infantil con manifestaciones de lupus profundo y alteraciones de la función pulmonar / Systemic lupus erythematosus of early appearance with manifestations of profund and pulmonary function involvement: study of one patient and review of the literature

Paciente femenina con lupus eritematoso sistémico y alteraciones de la función pulmonar que desarrolló manifestaciones cutáneas de lupus profundo. No se encontró en la literatura pediátrica revisada esta asociación. Se trató con esteroides de dosis bajas, cloroquina y ciclofosfamida con lo que desaparecieron todas las manifestaciones. La frecuencia de paniculitis lúpica en niños admitidos en el Instituto Nacional de Pediátria de 1970 a 1991 es del 1.4 por ciento, similar al 2 por ciento descrito en adultos