Urticarial Plaques With Vesicles in a Young Hispanic Woman

A 22-year-old Hispanic woman with no prior medical history presented with a 4-month history of disseminated skin lesions. Initially, she developed pruritic papules and urticarial plaques in the perioral region, which progressively spread to the neck, chest, and upper extremities. She had been treated with intramuscular dexamethasone (8 mg) and oral loratadine (10 mg every 12 h for 2 weeks), achieving partial improvement. Physical examination revealed polycyclic and annular erythematous plaques with an urticarial appearance and scarce, small vesicles at the periphery (Figure 1). The patient denied systemic symptoms, including asthenia, arthralgia, or fever. Initial laboratory work-up showed hemoglobin 12.9 g/dL, platelets 283 × 10⁹/L, white blood cells 6.0 × 10⁹/L, and no proteinuria. Two skin biopsies were obtained for histopathologic (Figure 2) and immunohistochemical evaluation (Figure 3).

The patient was initially treated with oral prednisone (0.5 mg/kg/day), hydroxychloroquine (0.5 mg/kg/day), and topical corticosteroids. After excluding glucose-6-phosphate dehydrogenase deficiency, dapsone (50 mg daily) was initiated, resulting in significant improvement of lesions within 3 weeks. The patient met the 2019 EULAR/ACR and 2012 SLICC classification criteria for systemic lupus erythematosus (SLE). She was referred to the Rheumatology department, where no additional organ or systemic involvement was identified.

BSLE is a rare cutaneous complication of SLE, with an estimated incidence of 0.19% [1, 2]. Similar to SLE, BSLE predominantly affects young women, often of African descent, in their second to fourth decades of life, although it can also occur in males and other races, or age groups [1, 3]. Autoantibodies targeting the NC1 and NC2 domains of type VII collagen are the immunopathologic hallmark of both BSLE and epidermolysis bullosa acquisita (EBA) [4]. In BSLE, these autoantibodies predominantly belong to IgG2 and IgG3 subclasses, whereas in EBA, they are primarily IgG1 and IgG4 [4]. Additionally, bullous pemphigoid (BP) antigens (BP180 and BP230), laminin 5, and laminin 6 may also contribute to its pathogenesis [5].

By definition, the diagnosis of BSLE requires that patients fulfill the ACR classification criteria for SLE [1, 2]. BSLE typically develops in patients with established SLE but can also present as the initial manifestation in 36%–40% of cases, with onset reported up to 18 years after SLE diagnosis [1, 3]. Clinically, it is characterized by an acute onset of tense vesicles and bullae containing clear or hemorrhagic fluid. These lesions may arise on both inflamed and normal skin, commonly involving sun-exposed areas but occasionally appearing on nonexposed regions [6]. The bullae typically evolve into erosions that heal without scarring, although residual hypopigmentation or hyperpigmentation is frequently observed. Pruritus is generally mild, though some patients report a burning sensation [2].

BSLE is rarely isolated and typically coexists with extracutaneous manifestations of SLE. In a recent study by de Risi et al. [3], moderate to severe disease activity was observed in most patients. Lupus nephritis was observed in 50% of cases, indicating that BSLE may serve as a marker of severe disease. However, it has been suggested that anti-collagen VII antibody levels correlate most strongly with disease activity [3]. Arthralgia or arthritis, and neurological involvement were reported in 50% and 20% of patients, respectively. Interestingly, in this case, BSLE was the initial feature of SLE, with no systemic involvement detected during a 1-year follow-up.

The histopathology of BSLE resembles dermatitis herpetiformis (DH), featuring subepidermal blistering, dermal edema, and a neutrophil-rich infiltrate in the upper dermis, which forms microabscesses within the dermal papillae [2]. Mucin deposits in the reticular dermis serve as a distinguishing feature of BSLE [6]. Classic features of other types of CLE are generally absent [3]. DIF study reveals lineal or/and granular deposits of IgG, IgM, and often IgA and C3 at the DEJ [2, 3]. Autoantibodies targeting the basement membrane zone can be detected by indirect immunofluorescence (IIF) and salt-split skin IIF in approximately half of cases, with predominant binding to the dermal side [1, 3]. More recently, an enzyme-linked immunoassay has been used to detect auto-antibodies against the NC1 and NC2 of type VII collagen [5].

Diagnostic criteria of BSLE were first described by Camisa [7] in 1983 and revised in 1988, incorporating clinical, histopathological, and immunopathological features. Ultimately, BSLE shares similarities with other primary bullous dermatoses, particularly with BP, DH, and EBA [2, 4, 8]. The overlapping patterns highlight the complexity of the diagnosis.

The LBT using a sample of clinically normal skin has been proposed as a useful diagnostic test for SLE. Nonlesion LBT shows high specificity (88.2%–98.8%), supporting its utility in confirming SLE, but its low sensitivity (17.6%–56.5%) limits its value for ruling out the disease [9, 10].

Dapsone is the first-line treatment for mild BSLE, with up to 90% efficacy and a rapid response within days. The typical dose starts at 50 mg daily, increasing to a maximum of 150–200 mg daily, but side effects occur in 23% of cases [3, 6]. For cases of intolerance, contraindications, or systemic SLE manifestations, immunosuppressants such as cyclophosphamide, mycophenolate mofetil, methotrexate, or azathioprine are recommended [1, 3, 6]. Rituximab has shown efficacy in refractory BSLE [11].

This case highlights the importance of recognizing BSLE as a rare manifestation of LES, particularly in underrepresented demographics such as Hispanic women [3]. Enhancing diagnostic accuracy across diverse skin phenotypes remains crucial in dermatology to ensure timely diagnosis and appropriate treatment in all populations.

Valeria Olvera-Rodríguez: conceptualization, acquisition of data, writing original draft preparation. Gerardo González-Martínez: conceptualization, acquisition of data. Sonia Chávez-Álvarez: investigation, supervision. Bárbara Sáenz-Ibarra: interpretation of histopathological and direct immunofluorescence studies of the skin. Minerva Gómez-Flores: supervision. Jorge Ocampo-Candiani: supervision. Erika Alba-Rojas: conceptualization, supervision, final manuscript approval.

All patients in this manuscript have given written informed consent for participation in the study and the use of their deidentified, anonymized, aggregated data and their case details (including photographs) for publication. Ethical Approval: Not applicable.

The authors declare no conflicts of interest.