A 9-year-old child with painful nodules on the leg

A 9-year-old girl presented with a 6-month history of painful erythematous nodules on her left thigh. There was no history of fever or trauma. Intense pain affected ambulation and on physical exam, the left leg was flexed and externally rotated. Skin exam showed erythematous nodules with microulcerations on the left leg from mid-thigh to the knee (Figure 1), with no lesions noted on the right leg. Dermoscopy demonstrated linear-branching vessels on a whitish background (Figure 2). Complete blood count (CBC), c-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and complement were normal. Antinuclear antibodies (ANA), extractable nuclear antibodies (ENA), serology for SARS-Cov2, Epstein Barr virus, cytomegalovirus, hepatitis B and C virus, and tuberculosis screen (QuantiFERON-TB Gold®) were negative. Expression of interferon-regulated genes (interferon signature) was normal. Urinalysis and fecal calprotectin were normal. Cardiac and abdomen ultrasound revealed no abnormalities. Biopsy of a skin lesion was performed (Figures 3 and 4). Histopathology showed a perivascular and periadnexal lymphocytic infiltrate in the dermis extending to the dermo-hypodermic interface. Within this lymphocytic infiltrate, small aggregates of epithelioid histiocytic cells were present. A lymphocytic infiltrate was also observed in the deep adipose tissue in a lobular pattern (Figures 3 and 4). Immunohistochemical stains of the lymphocytic infiltrate showed a presence of T lymphocytes (CD3+, with a presence of CD4+ elements) and a minority population of B lymphocytes (CD20+). Also, clusters of plasmacytoid dendritic cells (CD 123+) were detected. The cell proliferation index (Ki67) in the lymphocytes was low. Based on the histopathologic findings, lupus panniculitis (LP) was diagnosed. Magnetic resonance imaging showed signal hyperintensity of skin tissue and muscle, suggesting an inflammatory condition. The patient was treated with prednisone (2 mg/kg/day), subcutaneous methotrexate (15 mg/m2/week), and folic acid (7.5 mg on the day after methotrexate). Prednisone was tapered over 2 months. After 6 months of treatment, the erythematous nodules had completely disappeared and the patient was able to walk and run. LP is a rare variant of cutaneous lupus erythematosus with few cases reported in children in the literature.1, 2 It typically presents in the third to sixth decades of life with a female predilection. LP most often presents as recurrent subcutaneous nodules or plaques, sometimes ulcerated that may heal with scarring and lipoatrophy.1-5 In children, the most commonly involved areas are the face and upper limbs (66% and 40% of cases, respectively),3-5 while lower limbs are involved in few cases (20%).3-5 LP can arise on its own or in association with systemic lupus erythematosus (SLE) or discoid lupus erythematosus (DLE). In children with LP, the risk of progression to SLE is unknown.3-5 LP may also be present in association with other connective tissue disorders, such as scleroderma or polymyositis.6-8 The differential diagnosis for LP includes erythema nodosum, pancreatic panniculitis, morphea profunda, cold panniculitis, panniculitis associated with interferonopathies,9 and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), which may be clinically identical to LP.10 Laboratory testing, including ANA, ENA, inflammatory markers, complement, and CBC, can be normal as in our case, so histopathology is crucial to confirm a diagnosis of LP.1-4 Histopathologic features of LP are characterized by a lobular panniculitis with limited extension into adjacent septa, predominant lymphoplasmacytic infiltrate, clusters of plasmacytoid dendritic cells, hyalinizing fat necrosis and paraseptal nodular lymphocytic aggregates with plasma cells.1-4 Features of lupus erythematosus, such as follicular plugging and vacuolar alteration at the dermo-epidermal junction or superficial and deep perivascular lymphocytic infiltrate with histiocytes and plasma cells can be seen.1-4 In our patient, the intense lymphocytic infiltrate with extension to lobular fat tissue and not to the septa ruled out erythema nodosum. The absence of abundant, closely packed thickened hyalinized collagen bundles in the dermis and subcutaneous fat excluded morphea.8 Differentiating LP from SPTCL can be challenging. In fact, clinically LP and SPTCL can have a similar presentation. Patients with SPTCL often have constitutional symptoms such as fever and asthenia, leukopenia, and high ESR.10 In our patient, the lack of fever or other constitutional symptoms, the normal ESR and CRP, the of presence of clusters of plasmacytoid dendritic cells (CD 123+), and the low cell proliferation index (Ki67) in the lymphocytes on skin biopsy supported our diagnosis of LP.10 Treatment of LP depends on the severity of disease and location. In adult patients with localized skin disease, topical steroids or tacrolimus may be useful while children rarely respond to topical treatment.11 There is only one report of a child with LP responding to topical steroids.12 In the majority of patients systemic treatment with corticosteroids and antimalarial drugs such as hydroxychloroquine is needed.11 For more aggressive LP or recurrent disease, methotrexate, cyclophosphamide, cyclosporine, and rituximab may be required.1-5, 11, 13 Our patient presented with intense pain on walking and MRI showed the inflammation in the muscle, so systemic steroids and methotrexate were used LP is rare and difficult to diagnose, particularly in patients without SLE or DLE at presentation. Early diagnosis and treatment of LP in childhood are important to prevent complications, such as pain, scarring, lipoatrophy, and calcinosis. Open Access Funding provided by Universita degli Studi della Campania Luigi Vanvitelli within the CRUI-CARE Agreement.