Hypocomplementemic urticarial vasculitis (HUV) syndrome, or McDuffie syndrome, is a rare autoimmune disorder first described in 1973 (1). It typically affects individuals in the fourth to fifth decades of life and exhibits a marked female predominance, with a ratio of approximately 8:1 (2). The true incidence of HUV is difficult to ascertain due to its wide range of clinical manifestations, diagnostic challenges, and overall rarity, but it is estimated to be around 0.5 cases per 100,000 individuals (3). Although traditionally regarded as a distinct clinical entity, increasing evidence highlights its overlap with systemic lupus erythematosus (SLE) (4, 5). Both HUV and SLE are autoimmune diseases that share a spectrum of clinical and immunological features, including arthralgia, cutaneous involvement, and hypocomplementemia. However, they differ in underlying pathophysiology, prognosis, and therapeutic approaches. The polymorphic nature of HUV, which may occasionally include features typically associated with SLE, challenges the distinction between these two conditions. This overlap has prompted debate among researchers over whether HUV represents a distinct entity or falls within the broader spectrum of lupus-related disorders (6).

Accurate differentiation between HUV and SLE is crucial, as it influences diagnosis, treatment strategies, and long-term prognosis. Here, we present the case of a 34-year-old Tunisian man with overlapping features of both conditions. This rare association exemplifies the diagnostic and therapeutic challenges encountered in such cases and underscores the importance of comprehensive clinical assessment and targeted immunological evaluation.

A 34-year-old Tunisian patient with a history of appendectomy in March 2023 and recurrent episodes of spontaneously resolving subocclusive syndrome, was referred, in April 2024, to the internal medicine department for further investigation of inflammatory polyarthralgia associated with a skin rash that flared up and spontaneously regressed within 24 to 72 hours. There was no known family history of autoimmune disease. Upon physical examination, the patient was afebrile, had a papular, erythematous, edematous, annular rash on the trunk, neck, and palms, consistent with urticaria ( Figure 1 ). The clinical photographs do not fully capture the characteristic features of urticarial vasculitis, given the transient and migratory nature of the eruptions. The eruptions were notably associated with intense pruritus. Abdominal examination was normal. There was a red left eye, but no pain or visual acuity loss. Ophthalmologic examination revealed signs of episcleritis.

Biological tests revealed an inflammatory syndrome with a C-reactive protein (CRP) of 132 mg/l, and serum protein electrophoresis showed hypoalbuminemia (31 g/l), hyper-α1 (4.1 g/l), and polyclonal hypergammaglobulinemia (36.5 g/l). The complete blood count revealed microcytic hypochromic anemia (hemoglobin 9.8 g/dL, MCV 73 fL, reticulocytes 50.000/mm³, ferritin 427 µg/ml) and lymphopenia (930/mm³). Renal function was normal, and 24-hour proteinuria was negative. Hepatitis B and C and HIV viral serologies were negative.

On immunological workup, indirect immunofluorescence (IFI) on Hep2 cells revealed a speckled pattern of positive antinuclear antibodies (ANA) with a strong titer of 1/1600. Immunodot testing revealed positivity for anti-Sm (+++), anti-dsDNA (+++), and anti-SSA (++). The presence of anti-dsDNA antibodies was confirmed by IFI on Crithidia luciliae. Complement protein testing showed decreased C3 (0.677 g/L) and C4 (0.111 g/L) fractions, with a normal C1q level (0.199 g/L). The hemolytic complement test (CH50) was reduced to 66%. Anti-C1q antibodies were positive at 49 U/ml by enzyme immunoassay. ANCA testing by IFI was negative. Skin biopsy showed infiltration of the dermis and subcutaneous tissue by neutrophils and lympho-plasmacytes, with exocytosis along the vessel walls, consistent with leukocytoclastic vasculitis. Additionally, nuclear debris around the vessels and within the dermis, as well as extravasation of erythrocytes between collagen fibers and the dermis, were observed ( Figure 2 ).

Computed tomography of the abdomen performed during the episode of abdominal pain and subocclusive syndrome revealed rectosigmoid colitis associated with jejunal enteritis and moderate peritoneal effusion. A follow-up CT scan a week later showed complete regression of the inflammatory lesions ( Figure 3 ). A chest CT scan was unremarkable.

The diagnosis of SLE was made according to the 2019 EULAR criteria, based on the combination of inflammatory polyarthralgia, lymphopenia, a high-titer ANA, the positivity of specific antibodies like anti-Sm and anti-dsDNA, and consumption of C3 and C4 complement fractions. The diagnosis of HUV was also established based on the presence of two major criteria: chronic urticaria and hypocomplementemia, along with four minor criteria: leukocytoclastic vasculitis, recurrent abdominal pain, episcleritis, and the presence of anti-C1q antibodies.

The patient was initiated on hydroxychloroquine at a dosage of 5 mg/kg/day, resulting in a rapid clinical improvement. Within a few days, urticarial lesions and abdominal pain resolved, and polyarthralgia subsided. Over the 12-month follow-up, the patient remained clinically stable, with no recurrence of symptoms. He experienced no episodes of urticaria, abdominal pain, or lupus flares—particularly renal involvement. Urinalysis consistently showed no proteinuria, and serum creatinine levels remained within normal limits. Immunosuppressive therapy was not required; the patient continued hydroxychloroquine alone, which was well tolerated. This favorable course supports a conservative treatment strategy in selected cases with mild overlapping features and no major organ involvement. However, long-term prognosis remains closely tied to the extent of systemic involvement and the timely management of potential complications associated with both conditions.

HUV is a rare small-vessel vasculitis (7), first described and individualized in 1973 by McDuffie et al. (1), with an estimated incidence of 0.5 cases per 100,000 individuals (3). It typically affects females, with a mean age at diagnosis of 45 years (4). Idiopathic HUV is defined by two major criteria: chronic urticarial lesions and hypocomplementemia, along with at least two minor features such as leukocytoclastic vasculitis, arthralgia or arthritis, ocular inflammation, glomerulonephritis, abdominal pain, or anti-C1q antibodies (8). Historically, its diagnosis excluded conditions such as systemic lupus erythematosus (SLE), cryoglobulinemia, and hereditary complement deficiencies. However, increasing overlap between HUV and connective tissue diseases—particularly SLE—has been documented. HUV is reported in approximately 7–8% of SLE patients, and up to 54% of HUV patients may develop SLE during follow-up (5, 9). Although the clinical manifestations are similar, they primarily differ in frequency (2, 9) ( Supplementary Table S1 ).

This case underscores the diagnostic and therapeutic challenges associated with the rare overlap between Hypocomplementemic urticarial vasculitis (HUV) and systemic lupus erythematosus (SLE). These two conditions share key clinical, immunological, and pathophysiological features, suggesting they may exist along a continuum within the spectrum of autoimmune diseases. In our patient, the absence of major organ involvement and the favorable response to hydroxychloroquine monotherapy highlight the clinical heterogeneity of HUV-SLE overlap and support the potential for a conservative treatment approach in selected cases with mild-to-moderate disease. Nevertheless, due to the rarity and variable presentation of this overlap, individualized management remains essential. Further research is needed to better delineate the disease spectrum and to establish clear, evidence-based therapeutic guidelines for managing overlap syndromes.