Immune Complex-mediated Vasculitis Research Articles

Kidney involvement in myelodysplastic syndromes.

The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes. We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9g/g, and median serum creatinine was 3.2mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen. The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV.

APDS patients with immune-complex vasculitis and resolution with leniolisib

Activated phosphoinositide 3-kinase delta syndrome (APDS) is an inborn error of immunity with heterogeneous clinical manifestations of infections, immune dysregulation, autoimmunity; lymphoproliferation; and malignancy. Immune complex-mediated vasculitides have not yet been described in APDS patients. Here we offer a case series of three patients with APDS who have refractory IgA vasculitis (also called Henoch-Schönlein purpura), a form of immune complex-mediated vasculitis that activates complement and attracts neutrophils, macrophages and eosinophils to cause local tissue injury. Leniolisib is an inhibitor of PI3K p110δ and an FDA-approved treatment for APDS. IgA vasculitis resolved upon treatment with leniolisib. Patients with immune dysregulation including IgA vasculitis should be screened for APDS.

Ambroxol-induced leukocytoclastic vasculitis: A case report and literature review

Cutaneous leukocytoclastic vasculitis (LCV) that primarily affects the skin, can be idiopathic or linked to infections, autoimmune diseases, neoplasms, and medications. An immune complex-mediated vasculitis of the dermal capillaries and venules is the histological hallmark of LCV, a small vessel vasculitis. This case report describes a 36-year previously healthy man who was presented to the outpatient department (OPD) with complaints of edema and development of numerous reddish-purple patches (caused by petechiae) after intake of cough syrup containing ambroxol. Ambroxol affects human monocytic cells THP-1, and prevents the generation of platelet-derived growth factor (PDGF)-AB that is produced by lipopolysaccharide (LPS) by inhibiting the expression of PDGF-A messenger Ribonucleic acid (RNA). An extracellular signal-regulated kinase (ERK) on p44/42 is activated by LPS, and ambroxol reduces this activation. In addition, 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD 98059), a Mitogen-Activated Protein Kinase Inhibitors (MEK), MEK-1-specific inhibitor, prevents p44/42 ERK activation and PDGF synthesis brought on by LPS. Megakaryocytes, erythrocytes, leukocytes, and their progenitors are stimulated to multiply by PDGF to the numerous endogenous growth factors that mesenchymal stem and stromal cells secrete. Ambroxol reduces the number of megakaryocytic progenitors and boosts apoptosis by inhibiting the production of PDGF and related signaling pathways. It is strongly advised that patients must be made more aware of the risks associated with using such over-the-counter medications.

Diagnosis and management of autoimmune diseases in the ICU.

Autoimmune diseases encompass a broad spectrum of disorders characterized by disturbed immunoregulation leading to the development of specific autoantibodies, resulting in inflammation and multiple organ involvement. A distinction should be made between connective tissue diseases (mainly systemic lupus erythematosus, systemic scleroderma, inflammatory muscle diseases, and rheumatoid arthritis) and vasculitides (mainly small-vessel vasculitis such as antineutrophil cytoplasmic antibody-associated vasculitis and immune-complex mediated vasculitis). Admission of patients with autoimmune diseases to the intensive care unit (ICU) is often triggered by disease flare-ups, infections, and organ failure and is associated with high mortality rates. Management of these patients is complex, including prompt disease identification, immunosuppressive treatment initiation, and life-sustaining therapies, and requires multi-disciplinary involvement. Data about autoimmune diseases in the ICU are limited and there is a need for multicenter, international collaboration to improve patients' diagnosis, management, and outcomes. The objective of this narrative review is to summarize the epidemiology, clinical features, and selected management of severe systemic autoimmune diseases.

#2663 KIDNEY INVOLVEMENT IN MYELODYSPLASTIC SYNDROMES

Abstract Background and Aims Myelodysplastic syndromes (MDS) are hematologic disorders characterized by ineffective and dysplastic hematopoiesis that can be associated with systemic inflammatory and autoimmune diseases. The objective of this study was to describe kidney involvement in MDS patients, their treatments, and outcomes. Method We conducted a French and American multicenter retrospective observational study in nine centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results Seventeen patients (males n = 11, median age 76 [70-79]) developed a kidney disease 6 months [0-31] after the diagnosis of MDS. Median urinary protein to creatinine ratio was 1.9g/g [0.8-3.3], and median serum creatinine was 3.5mg/dL [1.5-4.7]. Twelve patients (70%) had AKI at presentation, and 14 (82%) extra-renal symptoms, which consisted mostly in cutaneous and pneumological manifestations. The renal diagnoses included antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis (AAV) (n = 8, 47%), ANCA negative vasculitis (n = 4, 24%), C3 glomerulonephritis (n = 2), immune complex-mediated glomerulonephritis (n = 1), polyarteritis nodosa (n = 1), and IgA vasculitis (n = 1). Kidney biopsies were performed in 10 of the cases. All patients, except one, received a treatment following the MDS-associated kidney injury (n = 16, 94% with steroids). The effect of MDS treatment on kidney injury could be assessed in 8 patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 9 months [4.1-14.2], 4 patients had CKD stage 3, 4 CKD stage 4, 5 an end stage kidney disease. Three patients evolved to an acute myeloid leukemia (AML), and 3 died. Compared to 84 MDS controls, patients who had a kidney involvement were younger (p = 0.03), had a higher number of dysplasia lineages (3 lineages, p = 0.001), and were more eligible to receive hypomethylating agents (p = 0.031), but no survival difference was seen between the two groups (p = 0.5227). Compared to 265 AAV without MDS, MDS-associated AAV were older (p = 0.019), ANCA serology was more frequently negative (p = 0.014), and more cutaneous lesions were seen (p = 0.003). Conclusion The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis, and especially AAV. A diagnosis of ANCA vasculitis in an elderly patient, or with a cutaneous manifestation, or without ANCA positivity, should lead to the search for a possible MDS.

Immunoglobulin A vasculitis (IgAV)

IgA vasculitis (IgAV) is an immune complex-mediated vasculitis characterized by IgA1-dominant immune deposits in small vessels. It is the most common systemic vasculitis in childhood with a mostly uncomplicated and self-limiting course. Adults are less affected but the course is frequently more complicated and more frequently accompanied by renal involvement. IgAV characteristically manifests itself on the skin with palpable purpura and in joints, the kidneys and the gastrointestinal tract. In cases of incomplete or atypical symptoms adifferential diagnostic work-up is required. Anumber of triggers have been suggested, especially infections and drugs. Disease management is tailored to organ manifestations and the severity of the symptoms. For children, optimized supportive care and targeted symptom relief are usually sufficient. Management of renal and gastrointestinal manifestations follows recommendations for ANCA-associated vasculitis and IgA nephropathy. Treatment options include glucocorticoids and immunosuppressive agents with varying and mostly insufficient evidence.

End-Stage Renal Disease, Autoimmune Hepatitis, Alveolar Hemorrhage and ANCA Vasculitis as a Complication of Chronic Hepatitis B Virus: An Unusual Case Report

Background: End stage renal disease, autoimmune hepatitis and alveolar hemorrhage have rarely been reported as the complications of hepatitis B virus infection that can potentially be triggered by an antibody-mediated vasculitis as a result of a viral infection. The following was a case report detailing a patient presenting with all three of the above presentations who was cytoplasmic antineutrophil cytoplasmic antibody-positive and a chronic carrier of hepatitis B virus. Case presentation: A 52-year-old Malagasy woman presented in our intensive care unit for acute respiratory failure with end-stage renal disease and deterioration in general condition. She was managed with steroids, non-invasive ventilation, and hemodialysis. Laboratory test showed elevated levels of serum creatinine and liver enzymes. An extensive workup was done to find the etiology of elevated liver enzymes. Only blood work that came back positive was for chronic inactive hepatitis virus B and positive autoantibody suggestive of autoimmune hepatitis. A computed tomography scan of her lung revealed features suggestive of bilateral alveolar hemorrhage. Workup for other causes of vasculitis, including anti-neutrophil cytoplasmic antibodies (ANCA) was positive for c-ANCA antibody to proteinase 3. Medical investigations allowed excluding other infectious diseases, malignancies and other rheumatic and vasculitis affections. Administration of lamivudine® orally was done. The patient was followed for more than one year and there were no other new systematic symptoms. Conclusion: This case report showed the possibility of hepatitis B virus-induced vasculitis as the cause of alveolar hemorrhage, autoimmune hepatitis, and end stage renal disease. The origin of these symptoms was attributed to immune complex-mediated vasculitis induced by antineutrophil cytoplasmic antibody.

Skin testing might have a diagnostic role in immune complex-mediated hypersensitivity reactions.

Clinical applications of skin testing are known to help diagnose IgE-mediated and T-cell-mediated delayed cutaneous reactions. By contrast, drug-induced immune complex-mediated vasculitis is primarily diagnosed based on medical history, clinical setting and laboratory evidence of immune-complex formation, as there are no proven methods to identify the suspect culprit. We report three cases of drug- or biologic-induced immune complex-mediated vasculitis, in which the culprit agents could be confirmed by a positive intradermal test with later reading (between 12 and 24 h after the test), with verification by immunohistochemical or immunofluorescent results. The findings of our study suggest that skin tests with a delayed reading could have a potential role in diagnosing some instances of immune complex-mediated hypersensitivity reactions.

Recent topics related to etiology and clinical manifestations of cutaneous arteritis.

Cutaneous polyarteritis nodosa (cPAN) was first reported by Lindberg in 1931. It has been recognized as a skin-limited vasculitis whose cutaneous histopathological features are indistinguishable from those of PAN. Cutaneous arteritis (CA) was defined as a form of single-organ vasculitis in the revised Chapel Hill Classification and was recognized as the same disease as cPAN. It became known that deficiency of adenosine deaminase 2 (DADA2) cases were included in cases that had been diagnosed with CA. Because of their similarity and differences in the treatment methods, DADA2 should be considered in CA cases, especially if they are diagnosed or developed in early childhood. Cutaneous arteritis may be classified as an immune complex-mediated vasculitis. It was reported that the pathogenesis of anti-lysosomal-associated membrane protein-2 (LAMP-2) antibodies and anti-phosphatidylserine-prothrombin complex (PS/PT) antibodies as good parameters in CA. The main skin manifestations include livedo racemosa, subcutaneous nodules, and ulcers. Although CA is recognized to have a benign clinical course, it has become known that it is easy to relapse. The existence of skin ulcers upon diagnosis or sensory neuropathies was suggested to be a predictor of poor prognosis. Cutaneous arteritis with them may need to be treated with more intensive therapies.

Hepatitis Virus C-associated Nephropathy: A Review and Update.

Hepatitis C virus (HCV) infection causes hepatic and extrahepatic organ involvement. Chronic kidney disease (CKD) is a prevalent non-communicable disorder, accounting for significant morbidity and mortality worldwide. Acute kidney injury and CKD are not uncommon sequels of acute or chronic HCV infection.The pathogenesis of HCV-associated kidney injuries is not well explored. Excess cryoglobulin production occurs in HCV infection. The cryoglobulin may initiate immune complex-mediated vasculitis, inducing vascular thrombosis and inflammation due to cryoglobulin deposits.Furthermore, direct damage to nephron parts also occurs in HCV patients. Other contributory causes such as hypertension, diabetes, and genetic polymorphism enhance the risk of kidney damage in HCV-infected individuals. Implementing CKD prevention, regular evaluation, and therapy may improve the HCV burden of kidney damage and its related outcomes.Therefore, in this review, we discuss and update the possible mechanism(s) of kidney injury pathogenesis with HCV infection. We searched for related published articles in EMBASE, Google Scholar, Google, PubMed, and Scopus. We used various texts and phrases, including hepatitis virus and kidney, HCV and CKD, kidney pathology in viral hepatitis, kidney transplantation in HCV-infected patients, kidney allograft survival in viral hepatitis patients, mechanism of kidney pathology in viral hepatitis, dialysis and viral hepatitis, HCV infection and kidney injuries, and viral hepatitis and CKD progression, etc. to identify relevant articles.

IgA vasculitis - similarities and differences to IgA nephropathy

IgA vasculitis - similarities and differences to IgA nephropathy Abstract. IgA vasculitis (IgAV), formerly called Henoch-Schönlein Purpura (HSP) is an immune complex-mediated vasculitis of small vessels typically affecting the skin, gastrointestinal tract, and the kidneys. Based on distinct histopathological and pathophysiological commonalities of IgAV and IgA nephropathy (IgAN) they are viewed as part of a spectrum of IgA-mediated inflammatory syndromes. While the disease course in children is most often benign, IgAV has a high risk of renal and gastrointestinal complications when first appearing in adulthood. Acute morbidity and mortality in IgAV are determined by gastrointestinal complications such as intussusception or perforation, while chronic morbidity depends on renal involvement. Nephritis symptoms can appear, subclinically, many weeks after the initial manifestation of IgAV, and can therefore be missed. Continuous monitoring of renal parameters and blood pressure is therefore recommended even after apparent remission of the disease. As there are no data from randomized controlled trials available, the treatment of IgAV is currently based on consensus-based expert opinions.

Immunoglobulin A vasculitis post‐severe acute respiratory syndrome coronavirus 2 vaccination and review of reported cases

Immunoglobulin (Ig)A vasculitis/nephropathy is a systemic immune complex‐mediated vasculitis. Although severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination is widely recommended in individuals without specific allergy to the vaccine components, it is arguable whether vaccination is advisable for patients with IgA vasculitis or for predisposed individuals. We and others have presented cases of IgA vasculitis occurring after SARS‐CoV‐2 vaccination. In total, these 19 cases, including ours, involved predominantly female patients, and half of them were suffering from de novo vasculitis onset. The most frequent manifestation was gross hematuria (89.5%) while skin lesions were relatively infrequent, occurring in only five cases (26.3%), of which three (15.8%) were confirmed to be IgA vasculitis. Taken together, these cases suggest that SARS‐CoV‐2 vaccination might be a trigger for development/deterioration of IgA vasculitis/nephropathy.

Acute Hemorrhagic Edema following COVID-19 Infection

Background: Acute hemorrhagic edema of infancy (AHEI) is an immune complex-mediated leukocytoclastic vasculitis. Despite its worrisome appearance, it has a benign disease course with rare systemic involvement. Clinical Description: A 25-month-old male patient was brought to the pediatric outpatient clinic with a pink oval-shaped plaque-like rash all over the body and edema on the lower extremities and left auricle. The child was diagnosed as a case of coronavirus disease 2019 (COVID-19) 5 days before the present complaints. History and physical examination were otherwise unremarkable. Because of the patient's age, the purpuric appearance of lesions, distribution pattern of the rashes, localized edema, and no end-organ involvement, a possibility of AHEI, triggered by COVID-19, was considered and the patient was evaluated for the same. Management and Conclusions: The patient recovered in 15 days with no end-organ involvement. He was advised to continue regular follow-ups to look for long-term complications. AHEI is a benign condition which may occur in children following COVID-19 infection. It is essential to recognize the condition to avoid unnecessary investigations and treatment.

Case Report on Systemic Lupus Erythematosus

Background: Systemic Lupus Erythematous (SLE) is a multi-system chronic but often episodic,autoimmune condition defined by widespread inflammation of connective tissues and immune complexmediated vasculitis as well as the involvement of Antinuclear Antibodies.Case Presentation: The 11 years old female patient who was apparently alright 2 months back admittedin “Acharya Vinoba Bhave Rural Hospital Sawangi (M), Wardha,” Maharashtra on date 22/02/2020 withthe chief complaint of high-grade fever on and off since 2 months and facial puffiness since 6 days, ascites,constipation and pain in joints. The patient started experiencing fever 02 months back which was highgrade and she took treatment on an OPD basis but there was no relief. After that she was admitted at GMCChandrapur for the complaint of cough, cold, fever and oral ulcer and symptomatic treatment was given andgot discharged after 12 days. Fever, facial puffiness, pain in knee joints. The patient had undergone variousinvestigations like complete blood count, urine analysis, lipid profile, anti-nuclear antibodies (ANA), ANTIDSDNA (Anti-Double Stranded DNA). The patient was treated with antibiotics, corticosteroid, antacid,DMARD (Disease-Modifying Anti-Rheumatic Drug), a loop diuretic, antiemetic and oral paste to treatmouth ulcers. Monitor all vital signs, checked and recorded intake and output, administered medication asprescribed.Conclusion: The patient was admitted to AVBRH with chief complaints of fever on and off, facial puffiness,ascites, constipation and pain in joints. Immediate treatment was started by health team members and nowthe patient’s condition is satisfactory.

S2300 Henoch-Schönlein Purpura Induced Terminal Ileitis Mimicking Crohn's Disease

INTRODUCTION: Henoch-Schönlein purpura (HSP), also known as immunoglobulin A (IgA) vasculitis, is an acute generalized immune complex-mediated small-vessel vasculitis. It characteristically presents with palpable purpura on buttocks and lower extremities. Renal dysfunction, joint involvement and gastrointestinal (GI) symptoms are also frequently seen. Although gastrointestinal involvement is common, it primarily shows up in the form of nonspecific symptoms such as abdominal pain, nausea, vomiting, diarrhea or constipation. Terminal ileitis associated with HSP has rarely been reported in the medical literature. CASE DESCRIPTION/METHODS: A 22-year-old male presented with bilateral knee arthralgia, abdominal pain and intractable nausea and vomiting accompanied by a non-blanching erythematous coalescing maculopapular rash on the dorsal aspect of the feet and around the ankles bilaterally (Figure 1). CT (Figure 2) showed fold thickening of proximal loops of jejunum and wall thickening and luminal narrowing of the terminal ileum extending several centimeters proximally. Fluid-filled mildly dilated small bowel loops measuring up to 3 cm in diameter were visualized. Additionally, significant abdominal and pelvic ascites was noted. There was no evidence of bowel obstruction. During colonoscopy (Figure 3), granular, erythematous, ulcerated, hemorrhagic and ecchymotic mucosa was visible in the terminal ileum. There was blood in the terminal ileum and the colon. However, no discrete areas of bleeding were identified. These findings were consistent with moderate to severe active terminal ileitis. A skin biopsy was performed which confirmed the diagnosis of HSP. Methylprednisolone was commenced and the patient experienced relief in his GI symptoms. DISCUSSION: Although terminal ileitis is the pathognomonic hallmark of Crohn’s disease, it is important to consider alternative causes such as HSP in the differential diagnosis of ileitis indicative of Crohn’s disease. The resemblance between inflammatory lesions in the terminal ileum in HSP and those seen in Crohn’s disease hints at a potential pathophysiological link between the two disorders which is supported by an emerging body of literature.Figure 1.: Non-blanching erythematous coalescing maculopapular rash on the dorsal aspect of both feet and around the ankles.Figure 2.: CT Abdomen & Pelvis Coronal Section: small bowel inflammatory changes involving the jejunum and ileum.Figure 3.: Colonoscopy showing moderate to severe active terminal ileitis.

Leukocytoclastic vasculitis as a rare dermatologic manifestation of Crohn\u2019s disease mimicking cellulitis: a case report

BackgroundLeukocytoclastic vasculitis (LCV) is an immune-complex mediated vasculitis characterized by neutrophilic inflammation and nuclear debris in post capillary venules. LCV is a rare dermatologic manifestation of Crohn’s disease (CD) and may occur with the onset of the disease or any time after the diagnosis including the period of exacerbation.Case presentationWe present a 70 year old woman with history of psoriasis and treatment refractory CD requiring monoclonal antibody therapy with ustekinumab. One month prior to the current admission, she developed abdominal pain, worsening diarrhea and was diagnosed with CD exacerbation for which she was given ustekinumab. While her abdominal symptoms mildly improved with ustekinumab, she developed new bilateral lower extremity rash initially treated with levofloxacin for presumed cellulitis. The rash consisted of mild erythematous, non-scaling patches with scattered non-palpable petechiae on the lower extremities with subsequent involvement of abdomen, lower back and buttocks. Abdominal exam showed diffuse tenderness without mass, guarding or rebound while reminder of physical exam was unremarkable. Following the failure of antimicrobial therapy, she was diagnosed with LCV by skin biopsy. Complete work up was negative for infectious, malignant and inflammatory etiologies of LCV. Patient improved with increased dose of budesonide and subsequently continued to tolerate ustekinumab without recurrence of LCV.Discussion and conclusionLCV is a rare form of vasculitis and one of the rarest dermatologic manifestations of CD, appearing at any stage of the disease. LCV has been associated with autoimmune diseases, infections, specific drugs (levofloxacin, ustekinumab), and malignancy. Clinical presentation of LCV is variable and frequently mistaken for cellulitis. LCV should be considered in differential diagnosis of bilateral lower extremity rash in patients with CD after infectious, malignant and auto-immune/inflammatory etiologies are excluded. Unlike erythema nodosum (EN) and pyoderma gangrenosum (PG), LCV requires biopsy for diagnosis. Most patients respond well to steroids without scarring.

TYPE II MIXED CRYOGLOBULINEMIA-INDUCED HEART FAILURE

Type II mixed cryoglobulinemia can cause immune complex-mediated vasculitis with involvement of multiple organs. The impact of mixed cryoglobulinemia on the heart is controversial. We report a rare case of cryoglobulinemia-induced heart failure. A 66-year-old male with no significant past medical

A fatal case of severe gastrointestinal and renal involvement in Henoch–Schönlein purpura

Henoch-Schönlein purpura (HSP) is an immune-complex mediated vasculitis affecting small vessels with dominant IgA deposits. It is seen mostly in children, with a self-limiting disease, but can present with more severe clinical features in older patients, such as gastrointestinal (GI) involvement, with a propensity for rapid progression. In this report, we describe our experience with a male HSP patient who presented with pneumonia, palpable purpuric rash, severe GI involvement with hemodynamic compromise and acute kidney injury. Even though we escalated therapy over time given the lack of response with each previous strategy, with corticosteroids and cyclophosphamide, he developed massive lower gastrointestinal hemorrhage that was not responsive to any supportive measure and died as a result of hemorrhagic shock. There was no established protocol that guided this treatment due to lack of rigorous data, which emphasizes the need for more studies on adult HSP in order to establish the optimal management for HSP patients with severe gastrointestinal manifestations.

Cryoglobulinemia: An update in 2019.

Cryoglobulinemia is defined as the persistent presence in serum of abnormal immunoglobulins (Igs) that precipitate at low temperatures and dissolve again upon warming. Cryoglobulins may be composed only of a monoclonal Ig (simple type I cryoglobulinemia), of a monoclonal Ig bound to the constant domain of polyclonal Ig heavy chains (mixed type II cryoglobulinemia), or only of polyclonal Igs (mixed type III cryoglobulinemia). The manifestations of type I cryoglobulinemia are often related to intravascular obstruction, whereas those seen in the mixed cryoglobulinemias often originate in true immune complex-mediated vasculitis. The main clinical manifestations affect the skin (purpura, necrotic ulcers), joints, peripheral nervous system, and kidneys (membranoproliferative glomerulonephritis). Patients with type I cryoglobulinemia should be investigated for hematological malignancies (myeloma and B-cell lymphoma). Hepatitis C is the main diagnosis to consider in patients with mixed cryoglobulinemia, followed by connective tissue disease and B-cell non-Hodgkin's lymphoma. The treatment depends mainly on the cause of the cryoglobulinemia. For instance, hepatitis C virus (HCV) eradication is in order in patients with HCV-associated cryoglobulinemia vasculitis, and the underlying hematological malignancy must be treated in patients with type I cryoglobulinemia.

Systemic lupus erythematosus of the urinary tract: focus on lupus cystitis.

Systemic lupus erythematosus (SLE) frequently manifests as urinary tract disease, most commonly in the form of lupus nephritis. Bladder involvement in the disease course takes a subclinical form and may affect both children and adults. Lupus cystitis can precede SLE diagnosis and may present with very unspecific urinary and digestive tract symptoms or no symptoms at all. The exact mechanism of bladder inflammation in lupus is not fully understood; however, histopathological studies suggest a possible role of immune complex-mediated small vessel vasculitis. Lupus cystitis is a rare SLE manifestation, but poses a challenge for physicians, due to its complex diagnostics and treatment.