From membranoproliferative glomerulonephritis to a final diagnosis: Hypocomplementemic urticarial vasculitis syndrome

Membranoproliferative glomerulonephritis describes a glomerular-injury pattern common to a heterogeneous group of diseases. Evaluation based on clinical and laboratory presentation and immunofluorescence staining on kidney biopsy allows identification of underlying pathophysiological processes and may facilitate proper diagnosis and treatment. Hypocomplementemic urticarial vasculitis syndrome is a rare autoimmune disease of multi-organ involvement. The diagnosis is based on well-defined clinical and laboratory criteria. The pathophysiology is not completely understood but the presence of anti-C1q antibody seems to be involved. Renal involvement occurs in up to 50% of cases. It can be heterogeneous and can be indistinguishable from lupus nephritis. Serological findings and skin involvement distinguish these two entities. We report the case of a 40-year-old female who presented with urticarial skin lesions, hypocomplementemia and nephrotic syndrome. Kidney biopsy showed membranoproliferative glomerulonephritis with full house immune complex deposits. The diagnosis of hypocomplementemic urticarial vasculitis syndrome was made and the patient was successfully treated with prednisolone and mycophenolate mofetil.

Heart valve disease in hypocomplementemic urticarial vasculitis syndrome. From immune mediated degeneration to embolic complications of infective endocarditis. A case report

Introduction Hypocomplementemic Urticarial Vasculitis Syndrome is a rare disease due to small vessel inflammation and characterized by chronic urticarial vasculitis and arthritis. Multi-organ manifestations may include glomerulonephritis, ocular inflammation (uveitis, episcleritis), and recurrent abdominal pain. To our knowledge, just other nine cases of HUVS with cardiac valvular involvement have been reported in the literature. Case summary A 32-year-old woman presented to the emergency department because of a cerebral Haemorrhage. She suffered from a severe HUVS form with cardiac valvular involvement. In the previous years, she underwent cardiac surgery twice for aortic and mitral valves immune-mediated degeneration. The neurologic event was secondary to Listeria monocytogenes aortic endocarditis, complicated by a cerebral embolism and periaortic abscess. Discussion Patients with HUVS rarely present valvular heart disease. The latter is mostly secondary to an inflammatory process. Valve degeneration and immunosuppressive therapy increase the risk of infective endocarditis, with dramatic consequences for the prognosis of these patients. Valvular involvement is a sporadic but potentially fatal complication of HUVS, which should be taken in mind in the multidisciplinary evaluation of these patients.

DNASE1L3 Deficiency, New Phenotypes and Evidence for a Transient Type I Interferon Signaling

Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3 pathogenic variants have been associated to a lupus phenotype. It is unclear whether interferon signaling is sustained in DNASE1L3 deficiency in humans. Here we report four new patients carrying biallelic DNASE1L3 pathogenic variations, including two previously unreported mutations. Disease in one patient was characterized by lupus nephritis and skin lesions, while two others exhibited hypocomplementemic urticarial vasculitis syndrome. The fourth patient presented with early-onset inflammatory bowel disease. To explore whether or not the interferon cascade was strongly and sustainably induced, Interferon stimulated genes (ISGs) expression was assessed for each patient. Contrary to canonical type-I interferonopathies, we noticed a transient increase of ISGs in blood, which reverted to normal with disease remission. Reviewing previous reports, DNASE1L3-related disease appears to carry a significant risk of lupus nephritis and a poor outcome together with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). DNASE1L3 deficiency may share the pathogenesis with C1q deficiency by affecting efferocytosis, and this report suggests that interferon production is not directly driven by DNASE1L3 pathogenic variants.

Hypocomplementemic urticarial vasculitis syndrome presenting with bilateral scleritis

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare autoimmune disorder characterised by recurrent urticarial lesions and acquired hypocomplementemia with systemic manifestations. The authors present the case of a 70-year-old man who presented to the ophthalmology clinic with bilateral scleritis and ocular hypertension. He was diagnosed with HUVS after a 6-month period of bilateral scleritis, vestibulitis, significant weight loss, mononeuritis multiplex and recurrent urticarial vasculitis with pronounced persistent hypocomplementemia and the presence of anti-C1q antibodies. Disease control was eventually obtained with mycophenolate and prednisolone.

URTICARIAL VASCULITIS IN CHILDREN

URTICARIAL VASCULITIS IN CHILDREN O. M. Оkhotnikova, O. A. Oshlyanskaya Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine Abstract. Different autoimmune diseases can present with organs malfunctioning and chronic urticaria symptoms in particular such urticarial vasculitis. This variant of vasculitis can be a separate nosological form, which includes a rare disease as hypocomplementemic urticarial vasculitis syndrome. In addition to chronic urticaria symptoms, hypocomplementemic urticarial vasculitis syndrome is characterized by severe systemic manifestations in different organs, decreased serum level of complement components, and appearance of specific markers, such as anti-C1q-antibodies. The diagnosis is confirmed by the results of skin biopsy, which is the «gold standard» of diagnosis. The condition often requires combined treatment with two immunosuppressive drugs. Hypocomplementemic urticarial vasculitis syndrome is a very rare disease, but, because of the multisystem manifestations, it can be encountered by any specialist (pediatrician, general practitioner, allergist, rheumatologist, ophthalmologist, dermatologist, nephrologist, etc.), therefore doctors should consider this condition when dealing with such patients in order to reduce the risk of hypocomplementemic urticarial vasculitis syndrome misdiagnosis as the variants of chronic urticaria or another immunopathogenetic disease. That is why doctors should be well aware of the features of the course of this disease, not only to reduce the likelihood of erroneous diagnosis of urticarial vasculitis as chronic urticaria or another disease of immunopathological genesis, but also because modern therapy of these conditions is radically different from each other: сhronic idiopathic urticaria requires adherence to a modern patient management algorithm with the initial use of H1-antihistamines with a possible increase in the dose (up to a 4-fold increase), and with their low efficiency — the transition to the use of cytostatics, monoclonal antibodies against immunoglobulin E –omalizumab, and is extremely limited and only for short-term use of glucocorticosteroids. Key words: urticarial vasculitis, its forms, hypocomplementemia, chronic urticaria, children. Olena Okhotnikova MD, PhD, professor, Head Department of Pediatrics #1, Shupyk National Healthcare University of Ukraine, 9, Dorogozhytska str., 04112, Kyiv, Ukraine e-mail: [email protected] Аsthma and Allergy, 2021, 3, P. 16–29.

Kidney Involvement in Hypocomplementemic Urticarial Vasculitis Syndrome—A Case-Based Review

Hypocomplementemic urticarial vasculitis syndrome (HUVS), or McDuffie syndrome, is a rare small vessel vasculitis associated with urticaria, hypocomplementemia and positivity of anti-C1q antibodies. In rare cases, HUVS can manifest as an immune-complex mediated glomerulonephritis with a membranoproliferative pattern of injury. Due to the rarity of this disorder, little is known about the clinical manifestation, pathogenesis, treatment response and outcome of such patients. We describe here three cases of HUVS with severe renal involvement. These patients had a rapidly progressive form of glomerulonephritis with severe nephrotic syndrome against a background of a membranoproliferative pattern of glomerular injury with extensive crescent formation. Therefore, these patients required aggressive induction and maintenance immunosuppressive therapy, with a clinical and renal response in two patients, while the third patient progressed to end-stage renal disease. Because of the rarity of this condition, there are few data regarding the clinical presentation, pathology and outcome of such patients. Accordingly, we provide an extensive literature review of cases reported from 1976 until 2020 and place them in the context of the current knowledge of HUVS pathogenesis. We identified 60 patients with HUVS and renal involvement that had adequate clinical data reported, out of which 52 patients underwent a percutaneous kidney biopsy. The most frequent renal manifestation was hematuria associated with proteinuria (70% of patients), while one third had abnormal kidney function on presentation (estimated glomerular filtration (GFR) below 60 mL/min/1.73 m2). The most frequent glomerular pattern of injury was membranoproliferative (35%), followed by mesangioproliferative (21%) and membranous (19%). Similar to other systemic vasculitis, renal involvement carries a poorer prognosis, but the outcome can be improved by aggressive immunosuppressive treatment.