Lupus panniculitis (lupus erythematosus profundus [LEP]) is rare, affecting 1% to 3% of patients with cutaneous lupus erythematosus.^1,2 More common in women, lupus panniculitis presents with subcutaneous nodules or plaques on the upper body. The shoulder and upper arms are most frequently involved, but lesions can also occur on the face and buttocks and have been reported in unusual sites such as the breast,^3,4 orbit,^5,6 and periparotid fat.⁷ Epidermal changes compatible with features of discoid lupus may or may not be present.^8,9 Regression of active lesions often leaves persistent atrophy (Fig. 41-1), a characteristic feature that can lead to a retrospective diagnosis of lupus panniculitis.⁸

Lesions may be precipitated by trauma to the subcutaneous fat, such as from previous injections or excisions.¹⁰ Although up to 30% of patients with lupus panniculitis meet the criteria for a diagnosis of systemic lupus erythematosus (SLE),^11,12 the disease course tends to be relatively mild.⁸ The nodules may precede, occur simultaneously, or develop after other manifestations of systemic disease.¹³

Individual lesions of lupus panniculitis may be treated with topical or intralesional corticosteroids; however, in more widespread or persistent disease, systemic treatment with corticosteroids, hydroxychloroquine, or other immunomodulatory agents may be necessary to control disease progression.^8,9

There is a dense lymphocytic inflammatory infiltrate involving the lobules of the subcutaneous fat (Fig. 41-2). The infiltrate may contain plasma cells as well as eosinophils, which are typically not found in other forms of cutaneous lupus.^11,14,15 In about 50% of cases, there are features of DLE, including epidermal atrophy, basal vacuolar change, thickened basement membrane, increased dermal mucin, and a superficial and deep perivascular and periadnexal lymphocytic infiltrate.^9,11 In the remainder of cases, only the subcutis is involved with minimal or no epidermal change.⁸ Other features of lupus panniculitis include the presence of lymphoid follicles, often with germinal centers and numerous plasma cells,^8,11,14 nuclear dust,^9,11 and hyaline necrosis^9,11,16 (Fig. 41-3).

Direct immunofluorescence (DIF) of lesions of lupus panniculitis shows linear deposition of IgM and C3 along the dermoepidermal junction, indicative of a positive “lupus band” test.^8,11 This finding may be helpful in supporting a diagnosis of lupus panniculitis in cases that are clinically compatible with the disease but lacking definitive histologic findings.⁸

The most important differential diagnosis of lupus panniculitis is subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and primary cutaneous γ/δ T-cell lymphoma (PCGDTCL). The distinction between lupus panniculitis and SPTCL is especially problematic given the significant overlap in histologic findings and immunohistochemical studies.^9,16,17 Features common to both entities include lymphocytic atypia, hyaline necrosis of fat lobules, karyorrhexis (Fig. 41-4), and a lymphocytic vasculitis.^9,16 “Rimming” of adipocytes by atypical lymphocytes has been heralded as a clue to the diagnosis of SPTCL, but this feature has also been reported in cases of lupus panniculitis, perhaps making it a less helpful finding to distinguish the two entities.¹⁶ Atypical lymphocytes in both conditions can display variable loss of the T-cell markers CD3, CD5, and CD7^16,18; T-cell gene rearrangement studies do not necessarily clarify the situation.¹⁶ Lastly, the presence of clusters of CD123⁺ plasmacytoid dendritic cells has been suggested to support a diagnosis of LEP.^17,19

Table 41-1 highlights helpful features that favor a diagnosis of lupus panniculitis over SPTCL. However, these findings should be approached cautiously as there have been reports of several cases of SPTCL with overlapping clinicopathologic features of lupus erythematosus.^18,19,21 Additionally, SPTCL is associated with an autoimmune disorder in ∼20% of patients, with SLE being the most common presentation.⁹

The similarities in the histology of lupus panniculitis and SPTCL led Magro et al.¹⁶ to suggest that both entities lie on a disease spectrum that they called “subcuticular T-cell lymphoid dyscrasia”; however, this idea remains somewhat controversial.²²

The distinction between lupus panniculitis and cutaneous γ/δ T-cell lymphoma (CGD-TCL) has become significantly easier to achieve given the development of immunohistochemistry (IHC) targeting the specific T-cell receptors. Using IHC, T-lymphocytes in lupus panniculitis are βF1+ (expressing the γ/δ T-cell receptor) whereas T-cells in CGD-TCL are positive for the γ/δ T-cell receptor.^18,23 Additionally, the atypical lymphocytes in CGD-TCL have a cytotoxic phenotype with CD56 positivity and often are dual negative with CD4 and CD8.^18,23