Saudi Journal of Kidney Diseases and Transplantation

: 2017  |  Volume : 28  |  Issue : 4  |  Page : 929--933

Renal manifestations in hypocomplementic urticarial vasculitis syndrome: Is it a distinct pathology?

Badriya AlHermi, Zakiya Al Mosawi, Deena Mohammed 
 Department of Pediatrics, Salmaniya Medical Complex, Manama, Kingdom of Bahrain

Correspondence Address:
Badriya AlHermi
Department of Pediatrics, Salmaniya Medical Complex, P. O. Box 12, Manama
Kingdom of Bahrain


Hypocomplementic urticarial vasculitis syndrome (HUVS) is an autoimmune disease characterized by recurrent urticaria, arthritis, and glomerulonephritis (GN). Anti-C1q antibody is the marker of HUVS together with low levels of classical pathway complements which are C2, C3, C4, and C1q. We report a case of a 6-year-old boy who presented with episodes of rashes, injected conjunctiva, abdominal pain, and arthritis, diagnosed as HUVS. He had low C3, low CH50, normal C4, and positive C1q antibody. His urinalysis showed intermittent microscopic hematuria only. One year later, his laboratories showed persistent low C3 and positive Anti-ds DNA. The urinalysis showed hematuria, pyuria, and nephrotic-range proteinuria. Urine protein to creatinine ratio was 101.8 h mg/mmol. Kidney biopsy showed mesangioproliferative GN consistent with the diagnosis of HUVS. The patient was treated initially with prednisolone then azathioprine was added to the regimen. He showed good response with the disappearance of hematuria and proteinuria. Nine months later, he had no skin rashes with normal urinalysis and normal anti-ds DNA antibody. We report a case with HUVS and GN with positive anti-dsDNA antibody that revealed good response to combination of immunosuppressive therapy.

How to cite this article:
AlHermi B, Al Mosawi Z, Mohammed D. Renal manifestations in hypocomplementic urticarial vasculitis syndrome: Is it a distinct pathology?.Saudi J Kidney Dis Transpl 2017;28:929-933

How to cite this URL:
AlHermi B, Al Mosawi Z, Mohammed D. Renal manifestations in hypocomplementic urticarial vasculitis syndrome: Is it a distinct pathology?. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2020 May 31 ];28:929-933
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Full Text


Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a distinct entity characterized by recurrent urticaria, angioedema, arthritis, and glomerulonephritis (GN). Anti-C1q antibody is the marker of HUVS together with low levels of complements of classical pathway which include C2, C3, C4, and C1q. Criteria for HUVS diagnosis was established that makes HUVS a separate entity rather than other systemic vasculitides. Recently, the causative DNA mutation was identified in two families with autosomal recessive HUVS.[1],[2] We present a child with HUVS and demonstrate the outcome based on renal pathology findings.

 Case Report

A 6-year-old boy presented at the age of four years with recurrent episodes of rashes, periorbital puffiness, and eye redness, associated with abdominal pain for two months duration. He also complained of pain in extremities and swelling in the dorsum of hands, with morning pain and stiffness. He received antihistamine therapy to control his symptoms, and the symptoms did resolve spontaneously after two to three days.

His development was normal. Family history was negative for kidney or autoimmune diseases; the child is a product of a nonconsanguineous marriage.

On examination, he looked thin. Both his weight and height were on the 3rd centile for age. There were urticarial rashes on his abdomen and extremities with bilateral injected conjunctiva. Other systems were normal [Figure 1].{Figure 1}

Initial blood tests revealed: hemoglobin (Hb) 9.1 g/dL, white blood cell (WBC) 6.8 109/L, and platelets 438 109/L. Erythrocyte sedimentation rate, C-reactive protein, liver function tests, blood urea, and creatinine were normal. Antinuclear antibody (ANA), extractable nuclear antigen antibody (ENA), rheumatoid factor, and antistreptolysin O titer were negative. Serum complement levels showed C3: 57 mg/dL (N: 90–180), C4: 16 mg/dL (N: 10–40). Immunoglobulin’s (IgA, IgM, IgG and IgE) were normal. Viral serology was negative. Urine microscopy showed red blood cells (RBCs) of only 20–25/huff with protein: nil. The urine protein/creatinine ratio (PCR) was 9.1 mg/mmol (N: 0–22).

The patient continued to have frequent episodes of rashes, abdominal pain, joints pain, and red eyes. His urine analysis showed intermittent microscopic hematuria only.

Three months later repeated blood tests revealed persistent low C3, with low CH50 <10 u/L (N: 23–46), C2: 10.8 IL (N: 14–22), C1q: 53 IL (N: 50-250), positive C1q antibody, and C1 inhibitor 0.5 g/I (N: 0.18–0.33). Anticyclic citrulinated peptide antibody and antineutrophil cytoplasmic antibodies were negative. HLA class I testing revealed A23, B35.

One year later, his blood tests showed persistent low C3, positive Anti-ds DNA: 94.6 IU/mL (N: <10). The urinalysis showed protein++, Hb +, RBC 10–25/hpf, WBC 5–10/hpf. Blood urea 7.6 mmol/L, creatinine 40 pmol/L, serum albumin 32 g/L, and PCR were 101.8 h mg/mmol.

At this stage, the patient’s general condition was stable, and clinical examination only revealed scattered urticarial rash. We proceeded to kidney biopsy that showed mesangioproliferative GN (MesPGN) and mild tubulointerstitial damage with no evidence of crescents, but with deposits of IgG, IgM, IgA and C1q in capillary and mesangial deposition (3+), and membranous C3 deposits (3+) [Figure 2]a. The electron microscopy showed sub-endothelial and focal mesangial deposits consistent with immunoglobulin deposits [Figure 2]b and [Figure 2]c.{Figure 2}

Skin biopsy on a fresh rash was done at this stage as well, and the histological findings showed mild hyperkeratosis and mild diffuse mixed perivascular inflammation (focally rich in eosinophil) in the dermis, which was suggestive of urticarial vasculitis.

The patient was treated with pulses of intravenous methylprednisolone followed by oral prednisolone of 2 mg/kg/day. One month later, azathioprine was added since there was no improvement of renal investigations including renal function and urinalysis in aim to help reduction of steroid dosage and minimize adverse effects of steroids. Three months later, the hematuria resolved and the PCR normalized, even after tapering the steroid.

Nine months later, his weight and height increased to 10th centile for age. He had no skin rashes, and clinical condition was good. Urinalysis was still normal, and PCR was 11 mg/ mmol (N: 0–22). Anti-ds DNA antibody decreased to 12.1 IU/mL.


HUVS or McDuffie syndrome is a rare autoimmune disease affecting mainly the small vessels. It is described more often in adults, and the literature review revealed mostly case reports.[1],[3]

HUVS has many overlapping symptoms with other systemic diseases. Some authors have suggested the possible progression of HUVS to systemic lupus erythematosus (SLE) and others have considered it as a minor form of SLE. Yet, the overlapping picture of HUVS and SLE and renal histopathology and immunoflourescent findings in both diseases makes the diagnosis of HUVS uncertain.[4],[5] About 50% of HUVS cases had positive serum ANA while positive anti-dsDNA antibody and ENA are rarely seen and they were considered as exclusion criteria to HUVS.[1],[5]

However, Trendelenburg et al reported a case with positive anti-dsDNA when the patient developed criteria fulfilling SLE disease.[6] Anti-dsDNA antibody was detected in high titer in our case after he developed the significant proteinuria, it became negative one year after treatment, but he had no enough diagnostic criteria for SLE. Since our patient did notfulfil the criteria to diagnose SLE, we consider the positive anti-dsDNA antibody as a serological marker that could be detected in HUV syndrome when patient develops nephrotic range proteinuria.

The HUVS diagnosis can be confirmed by antibodies against C1q which is considered as a serological marker and almost exclusively in HUVS (100%). However, antibodies against C1q are not specific to HUVS alone; they have been observed in other immune-mediated disorders, such as its correlation with the renal flares in lupus nephritis (35%–48%).[7],[8] However, anti-C1q antibodies were detected in our patient since his initial presentation.

Renal involvement in HUVS was reported in more than 50% of the cases. The renal involvement can develop after many years of HUVS symptoms; delay is up to nine years post diagnosis. The renal manifestation ranges from mild proteinuria to nephrotic range, with variable degree of hematuria, or can present as rapidly progressive GN.[9],[10]

Renal biopsy is necessary if the patient has significant proteinuria with or without abnormal renal function. Renal pathology revealed mostly mesingio-or membranoproliferative glomerulonephritis, but focal proliferative GN, membranous GN, minimal change disease, and severe sclerosing proliferative GN were reported as well. Crescentic GN in HUVS is very rare. It has been reported in few cases only; some are children.[11],[12]

We observed the similarity in sequences of events in this patient with another patient which we presented in an earlier publication.[13] Both cases presented around age of three years with recurrent episodes of urticaria, eye redness, and arthritis followed by persistence of significant proteinuria that required kidney biopsy by the age of six years. A lag phase which may take few years between the initial symptoms and the appearance of proteinuria may underestimate the importance of the regular monitoring for renal involvement, especially that both patients were asymptomatic at the time of the proteinuria.

The renal pathology was suggestive of MesPGN in our current patient, but in our previous patient, mesangioproliferative with crescentic GN was seen.[13] Renal immunofluorescence findings in both of the patients were identical to findings in other reported cases which revealed C1q deposits and tubuloreticular inclusions in capillary endothelial cells.

There is no consensus on a specific treatment for HUVS. Multiple immunosuppressive drugs therapy has been used. Some of the common medications are corticosteroids, especially for the glomerular involvement. Other immunosuppressive drugs including azathioprine, mycophenolate mofetil (MMF), methotrexate, and cyclophosphamide alone or in combination with prednisolone were considered for refractory HUVS.[3],[14],[15]

Prednisolone alone was not sufficient to resolve the nephritis in both of our patients, for which second-line immunosuppression medications were necessary to prevent further renal progression. Azathioprine was able to control the GN in this case, but it failed to do so with the previous case for which we used MMF, and only Tacrolimus was able to control the progression of the GN.

Cyclophosphamide is one of the recommended medications for crescentic GN. Enríquez, reported 39-year-old women with HUVS, she had nephrotic syndrome with acute renal failure and crescentic membranoproliferative GN. She was treated initially with corticosteroids and cyclophosphamide with improvement of the renal function and partial remission of the nephrotic syndrome. Later, MMF as monotherapy was administered for nephrotic syndrome relapses, with reduction in proteinuria.[16]


We reported a case with HUVS and glomerulonephritis with positive Anti-dsDNA antibody that revealed good response to combination of immunosuppressive therapy.

Conflict of interest: None declared.


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