Panniculitis in childhood-onset systemic lupus erythematosus: a multicentric cohort study.

OBJECTIVE: To evaluate prevalence, clinical manifestations, laboratory abnormalities, treatment and outcome in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients with and without panniculitis. METHODS: Panniculitis was diagnosed due to painful subcutaneous nodules and/or plaques in deep dermis/subcutaneous tissues and lobular/mixed panniculitis with lymphocytic lobular inflammatory infiltrate in skin biopsy. Statistical analysis was performed using Bonferroni correction(p < 0.004). RESULTS: Panniculitis was observed in 6/847(0.7%) cSLE. Painful subcutaneous erythematosus and indurated nodules were observed in 6/6 panniculitis patients and painful subcutaneous plaques in 4/6. Generalized distribution was evidenced in 3/6 and localized in upper limbs in 2/6 and face in 1/6. Cutaneous hyperpigmentation and/or cutaneous atrophy occurred in 5/6. Histopathology features showed lobular panniculitis without vasculitis in 5/6(one of them had concomitant obliterative vasculopathy due to antiphospholipid syndrome) and panniculitis with vasculitis in 1/6. Comparison between cSLE with panniculitis and 60 cSLE without panniculitis with same disease duration [2.75(0-11.4) vs. 2.83(0-11.8) years,p = 0.297], showed higher frequencies of constitutional involvement (67% vs. 10%,p = 0.003) and leukopenia (67% vs. 7%,p = 0.002). Cutaneous atrophy and hyperpigmentation occurred in 83% of patients. CONCLUSIONS: Panniculitis is a rare skin manifestation of cSLE occurring in the first three years of disease with considerable sequelae. The majority of patients have concomitant mild lupus manifestations.

Panniculitis in childhood-onset systemic lupus erythematosus: a multicentric cohort study

Abstract Objective: To evaluate prevalence, clinical manifestations, laboratory abnormalities, treatment and outcome in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients with and without panniculitis. Methods: Panniculitis was diagnosed due to painful subcutaneous nodules and/or plaques in deep dermis/subcutaneous tissues and lobular/mixed panniculitis with lymphocytic lobular inflammatory infiltrate in skin biopsy. Statistical analysis was performed using Bonferroni correction(p < 0.004). Results: Panniculitis was observed in 6/847(0.7%) cSLE. Painful subcutaneous erythematosus and indurated nodules were observed in 6/6 panniculitis patients and painful subcutaneous plaques in 4/6. Generalized distribution was evidenced in 3/6 and localized in upper limbs in 2/6 and face in 1/6. Cutaneous hyperpigmentation and/or cutaneous atrophy occurred in 5/6. Histopathology features showed lobular panniculitis without vasculitis in 5/6(one of them had concomitant obliterative vasculopathy due to antiphospholipid syndrome) and panniculitis with vasculitis in 1/6. Comparison between cSLE with panniculitis and 60 cSLE without panniculitis with same disease duration [2.75(0-11.4) vs. 2.83(0-11.8) years,p = 0.297], showed higher frequencies of constitutional involvement (67% vs. 10%,p = 0.003) and leukopenia (67% vs. 7%,p = 0.002). Cutaneous atrophy and hyperpigmentation occurred in 83% of patients. Conclusions: Panniculitis is a rare skin manifestation of cSLE occurring in the first three years of disease with considerable sequelae. The majority of patients have concomitant mild lupus manifestations.

Lupus erythematosus panniculitis in a 10-year-old female child with severe systemic lupus erythematosus: A case report.

RATIONALE: Lupus erythematosus panniculitis (LEP) is a rare subset of lupus erythematosus. The incidence of LEP in systemic lupus erythematosus (SLE) ranges from 2% to 5%. In the previous literature, most LEP patients were women aged from 20 to 60 years, while pediatric cases were rare, all of whom appeared on their own without SLE.A rare LEP in a 10-year-old female child with severe SLE is presented. PATIENT CONCERNS: A 10-year-old girl was admitted to our hospital for marasmus and fatigue without other typical manifestations of SLE well before the appearance of skin lesions. The only proof to support the SLE is that we observed a weakly positive antinuclear antibody (ANA) in serum at the onset. DIAGNOSES: A 10-year-old girl diagnosed to the Division of Nephrology, Department of Pediatrics, the Second Xiangya Hospital, Central South University, for LEP with severe SLE. INTERVENTIONS: The patient was administered with high-dose corticosteroids and cyclophosphamide. OUTCOME: The patient died of severe lung involvement despite the use of high-dose corticosteroids and cyclophosphamide. LESSONS: This report highlights an unusual manifestation of LEP associated with SLE in a child. It also suggests that pediatricians should be aware of occult onset of SLE, such as unclear marasmus and fatigue found in this case. Repeat tests of antinuclear antibody and anti-double strand DNA antibody (anti-dsDNA) as well as renal biopsy in a timely manner will be effective to achieve early recognition and immediate treatment for saving lives.

Lupus Panniculitis as an Initial Manifestation of Systemic Lupus Erythematosus: A Case Report.

Lupus erythematosus panniculitis (LEP) is a variant of chronic cutaneous lupus erythematosus (CCLE). Reported cases of LEP lesions before the diagnosis of systemic lupus erythematosus (SLE) were very rare; only 9 cases have been reported, to the best of our knowledge. We now describe the case of a 19-year-old male patient, with an overall review of the English literature. In the earliest stage of the present case, nodules and ulcers involved his left leg and face, with no other accompanied symptoms. The skin lesions disappeared after treatment with methylprednisolone, 16 mg/d for 1 month. Seven months after discontinuing methylprednisolone, the cutaneous nodules and ulcers on his back recurred and were accompanied by fever, hair loss, and polyarthritis. Blood tests revealed leucopenia, positive antinuclear antibody and Smith antibody, and proteinuria. Histopathological findings were most consistent with LEP. This was followed sequentially by the diagnosis of SLE. The patient improved again after treatment with methylprednisolone and cyclophosphamide.Patients with LEP should have regular follow-ups because the development of SLE is possible. Early diagnosis and proper treatment is pivotal to improve the prognosis of such patients.

[Juvenile systemic lupus erythematosus with unusual manifestation of lupus-associated panniculitis]. / Juveniler systemischer Lupus erythematodes mit der ungewöhnlichen Manifestation einer Lupus-assoziierten Pannikulitis.

Juvenile systemic lupus erythematosus (JSLE) is a rare multisystem autoimmune disease with broad heterogeneity of clinical manifestations. Diagnosing JSLE is often very challenging. This life-threatening, unpredictable, and relapsing disease, which may affect various organ systems, requires interdisciplinary, lifelong care. Here, we report the case of a 13-year-old patient with JSLE suffering from recurrent arthralgia, lupus panniculitis, and rashes that were successfully treated with hydroxychloroquine and prednisolone.

Disseminated ulcerating lupus panniculitis emerging under interferon therapy of hairy cell leukemia: treatment- or disease-related?

We report a 43-year-old woman, who underwent therapy with interferon-α for hairy cell leukemia. During interferon-α therapy she developed multiple subcutaneous swellings, accompanied by fever and fatigue. A skin biopsy revealed lobular, T-cell lymphocytic panniculitis. In conjunction with the clinical and immunological findings, the diagnosis of lupus panniculitis was made and interferon-α therapy stopped. Initially, she responded well to oral prednisone and hydroxychloroquine, but after several months she became resistant to it. Her condition worsened, she developed skin ulcers in the inflamed regions. Only with the leukemia-targeted therapy using cladribine and rituximab her skin condition could be controlled, suggesting hairy cell leukemia as an additional trigger of the lupus panniculitis. Our report is the first one to show induction of lupus panniculitis under interferon therapy of hairy cell leukemia and its presumable sustentation by the latter.

Atypical lupus erythematosus panniculitis progressing to antinuclear antibody-negative systemic lupus erythematosus.

BACKGROUND: Lupus erythematosus panniculitis (LEp) is an uncommon but distinctive subset of lupus erythematosus (LE). It may develop in patients with discoid or systemic LE or may occur as an isolated phenomenon. CASE REPORT: We describe a case of LEp affecting unusual sites: the parotid gland, eyelid, and scalp. Subsequently, the patient progressed to antinuclear antibody-negative systemic LE.

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.

Peripheral T-cell lymphoma presenting as lipoatrophy and nodules.

BACKGROUND: Cutaneous lymphomas have many morphologic forms and clinical features. Lymphoma presents rarely with a constellation of nodules, panniculitis, and localized lipoatrophy. The histopathologic similarities of lymphoma and connective tissue disease panniculitis may create a diagnostic challenge. METHODS: We retrospectively reviewed the case of a 47-year-old man who presented 15 years earlier with recurrent fevers, fatigue, tender subcutaneous nodules, and facial, trunk, and extremity lipoatrophy. RESULTS: Initial biopsy of a cutaneous nodule showed lymphohistiocytic panniculitis without atypical inflammatory cells. Serologic tests showed negative connective tissue serologies, yet the initial clinical impression was most consistent with lupus panniculitis. Initially, the patient was treated with oral prednisone; later, steroid-sparing agents were used with modest improvement evidenced by resolution of his systemic symptoms and stabilization of the cutaneous findings. A decade later, more pronounced facial lipoatrophy, new facial nodules, and posterior thigh pain developed. Laboratory testing showed leukopenia, elevated liver and muscle enzymes, hypertriglyceridemia, and a low level of high-density lipoprotein. Biopsy of a new chin nodule indicated peripheral T-cell lymphoma, whereas an evaluation for systemic malignant involvement was negative. The patient was started on chemotherapy, which resulted in stabilization of the lipoatrophy and decreasing size and frequency of the cutaneous nodules, but the posterior thigh pain persisted. CONCLUSIONS: We report a rare case of lymphoma presenting as nodules and profound lipoatrophy, which exemplifies the complexity of lymphomas. Profound lipoatrophy and panniculitis may be an unusual and diagnostically challenging presentation of cutaneous lymphoma.

Borderline systemic lupus erythematosus (SLE): a separate entity or a forerunner to SLE?

AIM: To compare a subgroup of patients with borderline systemic lupus erythematosus (SLE) with those with classic lupus in order to determine whether the former subset is a separate entity or a forerunner to SLE. METHODS: A retrospective survey was undertaken of a database containing the clinical information of a total of 71 patients in an Abu Dhabi hospital setting over a 12-year period. Data of interest were criterial and non-criterial features of SLE together with relevant laboratory tests. RESULTS: Fifty-six patients had SLE and 15 were considered to have borderline SLE as they satisfied less than four criteria of classification. Age and female sex distribution were no different in the two subgroups, but the disease duration was shorter in patients with borderline lupus. The occurrence of arthropathy (non-erosive), serositis, thrombocytopenia, hemolytic anemia, and malar eruption was common to both subgroups. Patients with borderline SLE lacked other mucocutaneous manifestations of lupus and major organ disease involvement. A number of other clinical features were also observed in the latter subgroup, including antiphospholipid (APL) syndrome. In addition, patients with borderline SLE expressed a multiple autoantibody profile, but had lower titers of antinuclear factor (ANF) and anti-double-stranded DNA (anti-dsDNA) antibodies than those with classic SLE. None progressed to full-blown SLE after a mean period of follow-up of 21.2 months. CONCLUSIONS: In our patients, borderline SLE was milder than classic lupus, yet shared a wide spectrum of non-criterial features and also produced clinical subsets. The clinical heterogeneity and multiple antibody profile may suggest that borderline SLE is a forerunner to SLE rather than a separate entity. A regular and longer period of follow-up is required, however, to ultimately determine the fate of these patients.

[Cutaneous lupus erythematosus. Part 1: clinical manifestations and classification]. / Kutaner Lupus erythematodes. Teil 1: Klinik und Klassifikation.

Cutaneous lupus erythematosus (CLE) is a heterogenous disorder with a wide range of skin manifestations. Therefore, it has been difficult to develop a unifying concept for classifying CLE from the dermatologic perspective in the past. In 2004, the classification system was updated and includes now acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), and intermittent CLE (ICLE). Additional rarely described variants are not listed as separate entities but are included in the classical forms. Diagnosis of the different subtypes of CLE is made by considering genetic, clinical, histopathologic, and immunoserologic findings, with a systematic analysis of individual criteria. In the past years, the etiology and pathogenesis of CLE has been subject of intensive research and it has been shown by several groups that exogenous factors, such as ultraviolet light and drugs, can induce CLE. The first part of this review will enable the reader to identify the various clinical manifestations of CLE and to employ characteristic criteria to assess differential diagnostic considerations.

Paniculitis lúpica en un niño con lupus discoide crónico / Lupus panniculitis in a boy with chronic discoid lupus

La paniculitis lúpica o lupus eritematoso profundo (LEP) es una forma poco frecuente de lupus eritematoso, que suele presentarse en mujeres de edad media. Son raros los casos comunicados en edad pediátrica. Clínicamente se caracteriza por la presencia de nódulos firmes en cara, nalgas y parte proximal de extremidades con tendencia a dejar áreas deprimidas de atrofia cutánea en su resolución. Puede presentarse aislado o asociado a lesiones de lupus eritematoso discoide (LED) o lupus eritematoso sistémico (LES). La histología se considera característica. Se presenta el caso de un varón con lesiones de lupus discoide desde los 4 años de edad, que a los 12 años desarrolló lesiones de LEP (AU)

[A case of systemic lupus erythematosus complicated with psoriasis vulgaris].

A 49-years-old female admitted to our hospital because of skin eruptions on the extremities in 1985. She had suffered from polyarthralgia, skin eruptions since 1983. Physical examinations revealed discoid lesion, central nervous system involvement, and polyarthritis. Laboratory tests revealed leukopenia, thrombocytopenia, and hypocomplementemia. Antinuclear antibody, ant-DNA antibody, LE test were positive. From these findings, she was diagnosed as systemic lupus erythematosus (SLE). She developed lupus peritonitis in 1990 and 1994, which was successfully treated by steroid pulse therapy. Since then, the activity of SLE was in good control under administration of prednisolone 10 mg/day. Chilblain lupus was seen from 1993, Raynaud's phenomenon from 1996, and she further developed subcutaneous induration on her chest, back and upper extremities in 1999. Skin biopsy findings were compatible with lupus panniculitis. In 2002, erythematous patches with scales were observed on her right hand and left knee, and these skin lesions were histologically diagnosed as psoriasis vulgaris. An autoimmune response similar to SLE is speculated in psoriasis. We describe a rare case of SLE with various skin lesions including psoriasis vulgaris.

Paniculitis lúpica asociada a lupus eritematoso sistémico / Lupus panniculitis associated with systemic lupus erythematosus

La paniculitis lúpica o lupus eritematoso profundo es una paniculitis mixta de localización preferente a nivel facial, región proximal de extremidades, tronco o región glútea. Aparece en el 2% de los pacientes con lupus eritematoso. Los anticuerpos antinucleares son positivos en aproximadamente el 70% de los casos, pero sólo el 25%-50% cumplen los criterios de la American Rheumatism Association para considerarse lupus eritematoso sistémico. Presentamos a una mujer de 54 años de edad que presentó nódulos eritematosos de consistencia firme en región facial, tronco y glúteos. El estudio histopatológico mostró una paniculitis mixta con necrosis hialina de la grasa y calcificación. La analítica reveló linfopenia y anemia. Los anticuerpos antinucleares (ANA) y anti-ADN fueron positivos. Durante los meses previos la paciente había presentado artralgias y brotes de inflamación articular, sobre todo en muñecas y articulaciones interfalángicas de las manos. Estos hallazgos clínicos y serológicos fueron compatibles con el diagnóstico de paniculitis lúpica asociada a lupus eritematoso sistémico de intensidad leve. El tratamiento se realizó con antipalúdicos de síntesis y bajas dosis de corticosteroides, con lo que las lesiones regresaron, excepto la localizada en región glútea, que permaneció como una única placa, con intensa calcificación (AU)

Lupus profundus, indeterminate lymphocytic lobular panniculitis and subcutaneous T-cell lymphoma: a spectrum of subcuticular T-cell lymphoid dyscrasia.

INTRODUCTION: The diagnosis and classification of lymphocytic lobular panniculitis (LLP) has historically proven to be a difficult challenge. We encountered 32 cases of primary LLP which could be categorized as: 1) lupus erythematosus profundus (LEP) (19 patients); 2) an indeterminate group termed indeterminate lymphocytic lobular panniculitis (ILLP) (6 patients); and 3) subcutaneous T-cell lymphoma (SCTCL) (7 patients). OBJECTIVE: We attempted to better define the subtypes of LLP by morphologic, phenotypic and genotypic features and to correlate those features to clinical presentation and outcome. METHOD: Skin biopsy material was studied by conventional light microscopy, through immunophenotyping performed on sections from paraffin-embedded, formalin-fixed tissue and in some cases on sections of tissue frozen after receipt in physiological (Michel's) medium, and by polymerase chain reaction single-stranded conformational polymorphism analysis to assess for clonality of T-lymphocytes. Clinical features were correlated to histologic, phenotypic, and genotypic analyses. RESULTS: Patients with LEP had a prior diagnosis of LE or overlying skin changes which light microscopically were characteristic of LE. Patients with ILLP had no concurrent or prior history of LE, no systemic symptoms or cytopenias, and a clinical course not suggestive of lymphoma. Cases of SCTCL showed hemophagocytic syndrome and/or lesional progression with demise attributable to the disease. Lesions in all groups showed proximal extremity predilection. Females predominated in the LEP group. The average age of onset was 38, 40 and 55 years in the LEP, ILLP and SCTCL groups, respectively. Cytopenia was seen in 4 LEP patients; 1 also developed fever. In LEP and ILLP, lesions resolved with hydroxychloroquine and/or steroid therapy, with recurrences following cessation of therapy. In the SCTCL group 4 developed hemophagocytic syndrome, 4 died within 2 years of diagnosis, and 3 went into remission following chemotherapy. The LEP and SCTCL groups manifested histological similarities: dense perieccrine and lobular lymphocytic infiltration, lymphoid atypia, histiocytes with ingested debris, eosinophilic necrosis of the fat lobule and thrombosis. The atypical lymphocytes although pleomorphic did not have a cerebriform morphology. The infiltrate in ILLP had a similar cytomorphology and distribution with variable angioinvasion which in all save one case was of lesser intensity and was not associated with significant fat necrosis or vasculitis. Germinal centers, dermal/subcuticular mucin deposition and an atrophying interface dermatitis with hyperkeratosis and follicular plugging were largely confined to the LEP group. Erythrophagocytosis, characteristic of SCTCL, usually indicated a supervening subcuticular lymphoid dyscrasia when encountered in ILLP and LEP. SCTCL showed a selective loss of CD5 expression with or without diminution in CD7 and monoclonal CD3 expression. Of 4 cases studied, 3 showed a CD8 dominant infiltrate while 2 others exhibited CD56 and CD30 positivity, respectively. All cases of SCTCL with amplifiable DNA showed T-cell clonality. Similar molecular and phenotypic features indicative of subcuticular lymphoid dyscrasia were encountered in cases of LEP and ILLP including a reduction in CD5, CD7, and/or monoclonal CD3 expression, a preponderance of CD8 lymphocytes within the subcutaneous fat and T-cell clonality. These cases showed lymphoid atypia with variable erythrophagocytosis. Cases of phenotypically abnormal and/or clonal LEP showed one or more of local destruction, lesional size progression, fever, and cytopenias, but lesions responded to hydroxychloroquine and/or prednisone therapy and death attributable to panniculitis could not be documented. Cases that were phenotypically normal and without clonality had none of the aforesaid atypical clinical features. CONCLUSION: Lymphoid atypia, erythrophagocytosis, loss of certain pan T-cell markers, a reduced CD4/8 ratio and TCR rearrangement define subcuticular T-cell lymphoid dyscrasia, including a subset of LEP and ILLP. The subcuticular lymphoid infiltrates represent a spectrum of histologic, immunophenotypic, and molecular abnormalities which range from those which are clearly benign to those which are clearly neoplastic, and also encompasses those cases which defy precise classification into the two aforesaid poles.