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Anti-glomerular basement membrane (anti-GBM) disease and anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis are the main causes of pulmonary-renal syndrome (PRS). The concurrence of both ANCA - myeloperoxidase (MPO) and proteinase 3 (PR3) - and anti-GBM antibodies has been described, although positivity for all three antibodies has rarely been reported. The natural history of triple-positive patients as well as the best therapeutic approach remains unknown. We describe a case of an 80-year-old woman that presented to the emergency department with a 3-month history of progressive fatigue, malaise and anorexia, and 5 weeks of cough with blood-streaked sputum and progressive peripheral edema. Through the complementary study, a rare diagnosis of PRS with triple-seropositive for both ANCA (MPO and PR3) and anti-GBM antibodies was made in a patient with untreated chronic hepatitis B virus infection. She was treated with glucocorticoid, cyclophosphamide, plasma exchange and entecavir, with pulmonary recovery. Renal function did not improve. After 2 years, the patient is still in dialysis, but did not have relapse of alveolar hemorrhage and ANCA and anti-GBM antibody titers remain negative. The authors intend to warn to PRS, in particular this rare cause, since delaying diagnosis can lead to significant morbidity and mortality for patients. J Med Cases. 2021;12(10):405-410 doi: https://doi.org/10.14740/jmc3742

Hydralazine, an arterial vasodilator, is a widely used medication for the management of hypertension and heart failure, especially for patients who cannot tolerate the use of ACEIs or ARBs. It is generally well-tolerated and has a safe profile in pregnancy. However, hydralazine can induce immune-mediated side effects, such as hydralazine-induced lupus and less commonly hydralazine- induced ANCA vasculitis. The latter most commonly affects the kidneys with or without other organ involvement. There are several cases reported in the literature of hydralazine-induced ANCA associated vasculitis (AAV) that have pulmonary manifestations, also known as hydralazine- induced pulmonary-renal syndrome (PRS), a condition with a high risk of mortality. We are reporting a case of Hydralazine-induced ANCA associated glomerulonephritis with severe diffuse alveolar hemorrhage (DAH). In addition, we will review the current literature and discuss the importance of prompt diagnosis and early management to decrease mortality and morbidity associated with this serious condition.

Introduction Anti-glomerular basement membrane (anti-GBM) disease is a small vessel vasculitis affecting the renal and lung capillary beds. We aim to study the clinicopathological characteristics and predictors of poor outcome of this disease in our population. Materials and methods This is a 15 year retrospective, single center observational study of Indian cohort. Patients with biopsy proven anti-GBM disease were studied. Results Anti-GBM disease was found in 0.5% of the total cases. The mean age at presentation was 46.7 years. Compared to renal limited disease those with pulmonary-renal syndrome had a higher frequency of hypertension, oliguria, percentage of crescents, interstitial inflammation and glomerulosclerosis. Double positive (anti-GBM and ANCA antibodies) patients showed more of glomerulosclerosis, tubular atrophy/interstitial fibrosis (IFTA) as well as periglomerular granulomas on biopsy. Patient survival at one year was 40.4% and death censored renal survival was 9.7%. Factors affecting the dialysis dependency at presentation were oligoanuria (p = .04), creatinine levels >5.7 mg/dl (p = .003), and high mean anti-GBM titers (p = .008). Atypical cases accounted for 8.3% of these patients. Oligoanuria (HR = 5.0, p = .05), high serum creatinine (HR = 1.55, p = .05), severe glomerulosclerosis (HR = 1.09, p = .03), and IFTA (HR = 2, p = .04) were associated with poor renal outcome. Advanced age (HR = 1.92, p = .03), high serum creatinine (HR = 1.9, p = .04) and high anti-GBM titers (HR = 1.01, p = .03) were associated with poor patient survival. Conclusions Anti-GBM is a rare disease with poor prognosis and varied presentations. Patients with pulmonary-renal syndrome showed severe disease whereas double positive had more of chronic changes. The predictors of poor prognosis include advanced age, oliguria, serum anti-GBM levels, serum creatinine levels, degree of glomerulosclerosis and IFTA. Atypical anti-GBM cases should be kept in mind while evaluating renal biopsies.

Pulmonary-renal syndrome refers to the combination of elevated plasma creatinine concentration and/or abnormal urinalysis with diffuse alveolar hemorrhage, and involves both an urgent diagnostic approach and care. We report the case of a 24-year-old man presenting with diffuse alveolar hemorrhage as well as a nephritic syndrome associating kidney failure, moderate hypertension, hematuria and selective glomerular proteinuria. The initial high suspicion of anti-glomerular basement membrane (GBM) disease or ANCA-associated vasculitis justified intravenous pulse-corticotherapy in association with plasma exchange. Renal biopsy was remarkable for an IgA nephropathy, lesions of active thrombotic microangiopathy (TMA) and a positive staining for complement factor C4d. Because anti-GBM and ANCA antibodies returned negative, plasma exchange was discontinued, but oral corticosteroids were maintained to prevent alveolar hemorrhage recurrence. In the absence of renal function recovery, hemodialysis was initiated. TMA lesions are frequently seen in IgA nephropathy and are associated with a poorer prognosis. Complement activation seems to be involved in the development of those lesions and contributes to disease progression. Conversely, alveolar hemorrhage in the setting of IgA nephropathy is uncommon. It is thought to result from non-specific mucosal hemorrhage, an immune complex mediated basement membrane damage and an IgA-mediated capillaritis against basement membrane antigens.

The rare and severe adverse effects associated with coronavirus disease of 2019 (COVID-19) vaccination have been under-appreciated, resulting in many instances of inappropriate management. We describe the case of an elderly woman who developed anti-neutrophil cytoplasmic antibody-associated vasculitis with pulmonary renal syndrome approximately 3 weeks after the first dose of COVID-19 mRNA vaccination (Moderna). Her nasopharyngeal polymerase chain reaction test for the COVID-19 RNA virus was negative. Gross hematuria, heavy proteinuria, acute renal failure (serum creatinine up to 6.5 mg/dL), and hemoptysis coupled with a marked increase in serum anti-myeloperoxidase-O antibody were observed. Renal biopsy showed severe vasculitis with pauci-immune crescent glomerulonephritis. The pulmonary hemorrhage was resolved and renal function improved following combined plasma exchange and the administration of systemic steroids and anti-CD20 therapy. The early examination of urinalysis and renal function may be crucial for identifying glomerulonephritis and acute renal failure in susceptible patients after COVID-19 vaccination.

Background Pauci-immune crescentic glomerulonephritis (CrGN) is one of the most common etiologies of rapidly progressive glomerulonephritis. This condition presents with crescentic glomerulonephritis with little or no immunoglobulin staining and negative serological workup aside from a positive antineutrophil cytoplasmic autoantibody (ANCA). Typically, patients with pauci-immune CrGN have an underlying systemic small vessel vasculitis, but in rare cases, it presents without any known vasculitis or ANCA. Pauci-immune ANCA negative CrGN is often strictly isolated to the kidneys. In this case, we present a patient with ANCA negative, pauci-immune CrGN with severe diffuse alveolar hemorrhage. Case presentation A 66-year-old Hispanic woman with a past medical history of controlled hypertension presented with fatigue and dysphagia. On admission, her vital signs were significant for hypoxia on room air, and her physical exam was remarkable for crackles bilaterally. The initial laboratory results revealed anemia (hemoglobin 5.2 g/dL), hyperkalemia (6.3 mmol/L), elevated creatinine (4.50 mg/dL, with a baseline of 0.9mg/dL). Urinalysis showed moderate blood and urine protein (200 mg/dL). Urine microscopic examination showed 25-50 RBCs seen/high power field. The patient was admitted to ICU due to hypoxia, a computed tomography scan of the chest/abdomen/pelvis was obtained and revealed multifocal pulmonary consolidations. A blood transfusion was ordered. The patient began to have hemoptysis and subsequent bronchoscopy showed diffuse alveolar hemorrhage. ICU team proceeded to intubate her as the hemorrhage continued to worsen. Further workup revealed a positive anti-nuclear antibodies (ANA) of 1:40, but otherwise negative serologies including myeloperoxidase (MPO)-ANCA, glomerular basement membrane antibody, and anti-double stranded DNA. Kidney biopsy showed necrotizing glomerulonephritis with crescents and negative immunofluorescence. She was diagnosed with pauci-immune ANCA-negative vasculitis with associated diffuse alveolar hemorrhage and nephritis based on these results and was started on pulse-dose steroids. The patient was started on intravenous (IV) high-dose cyclophosphamide, which helped improved the overall clinical condition significantly. After creatinine began trending down and urine output improved, the patient was discharged on a regimen of daily oral cyclophosphamide and steroid taper. Patient oxygen requirements decreased and she was sent home with supplemental oxygen while requiring 3L/min of oxygen. Conclusion Pauci-immune and ANCA-negative glomerulonephritis with concurrent diffuse alveolar hemorrhage is exceptionally rare. In this situation, medical management relied on clinical evidence from similar populations in the use of steroids and cyclophosphamide. This case report aims to shed more light on the clinical progression and management of this condition. Here we present a case of pulmonary-renal syndrome with biopsy-proven glomerulonephritis but without ANCA positive serologies.

Granulomatosis with polyangitis (GPA) is characterized by a necrotizing granulomatous vasculitis of small arteries and veins. It most commonly affects the upper and lower respiratory tract and kidneys. However, other organs including the gastrointestinal tract can be affected. Gastrointestinal manifestations of GPA are rare and can include ischemia, bowel infarction, and perforation. Hemorrhage is an extremely rare presentation of GPA. We present a case of a woman with GPA and pulmonary renal syndrome on treatment who presents with severe gastrointestinal hemorrhage.

We present a series of two cases of ANCA associated Vasculitis (AAV) presenting as Pulmonary Renal syndrome with associated renal vein thrombosis. Although there are enough evidences suggesting association of venous thrombosis with AAVs, the incidence of renal vein thrombosis is rare. Renal vein thrombosis should be ruled out in cases where there is delay in recovery of renal function in patients with AAV. Positive laboratory values for anti-Proteinase-3 (PR3) and anti-Myeloperoxidase (MPO) ANCA in the cases that presented as Rapidly Progressive Glomerulonephritis, helped in early initiation of treatment with complete recovery of Renal function.

Pulmonary-renal syndrome has rarely been reported as the clinical presentation of vasculitis caused by the consumption of cocaine adulterated with levamisole. We report the case of a patient in whom we detected the clinical manifestations and indicate the difficulties that arose in relation to the diagnostic and therapeutic approach. RESUMEN: El síndrome pulmón-riñón rara vez ha sido reportado como cuadro clínico de presentación de vasculitis causada por el consumo de cocaína contaminada con levamisol. Se reporta el caso de un paciente con este cuadro clínico y se señalan las dificultades que se presentaron durante el abordaje diagnóstico y terapéutico. COL0010959

We present a 61-year-old male with FLT3-mutated acute myeloid leukemia treated with midostaurin who developed acute kidney injury requiring hemodialysis and pulmonary renal syndrome. Antibodies to proteinase-3, myeloperoxidase, and glomerular basement membrane were negative. Renal biopsy confirmed acute pauci-immune focal necrotizing glomerulonephritis (GN) with fibrin crescents indicating rapidly progressing glomerulonephritis. He improved with pulse methylprednisolone, intravenous cyclophosphamide, and plasma exchange with resolution of hemoptysis. This case highlights the importance of prompt renal biopsy to guide early initiation of life-saving therapies. To our knowledge, this is the first reported case of ANCA-negative pauci-immune necrotizing GN likely secondary to midostaurin.

A 63-year-old woman was admitted because of diffuse alveolar haemorrhage complicated with systemic sclerosis. High anti-RNA polymerase III (RNAP III) antibody titre was detected despite normal blood pressure and renal function. Antibodies other than anti-RNAP III antibody were negative. After initiation of methyl-prednisolone pulse therapy, the patient developed thrombotic microangiopathy (TMA) with exacerbation of respiratory failure, which required mechanical ventilation. However, renal function was preserved. We immediately started the patient on plasma exchange; subsequently, her diffuse alveolar haemorrhage and TMA dramatically improved. Diffuse alveolar haemorrhage with systemic sclerosis is generally occurred as pulmonary renal syndrome, and positive anti-RNAP III antibody is recognised as a predictive marker of scleroderma renal crisis. However, this case suggests that high anti-RNAP III antibody titre may play a role in the development of diffuse alveolar haemorrhage without scleroderma renal crisis.

In the article, we report the causes of pulmonary hemorrhage (PH) according to the literature data and own experience, with an emphasis on patients suffering from rheumatic diseases. Methods of diagnosis and modern approaches to the treatment of PH are analyzed.В представленной статье на основе данных литературы и собственного опыта приведены сведения о причинах легочных кровотечений (ЛК) с акцентом на пациентов, страдающих ревматическими заболеваниями. Проанализированы методы диагностики и современные подходы лечения ЛК.

The article analyzes the diagnosis and treatment of anti-GBM antibody disease (Goodpasture's syndrome) - a rare, severe progressive disease, associated with anti-glomerular basement membrane antibody-induced pulmonary hemorrhage and glomerulonephritis. The main problem of this pathology is late diagnosis, resulted in ineffective treatment. The article provides current information on the epidemiology, etiology and pathogenesis, diagnosis, and treatment of Goodpasture’s syndrome, as well as clinical case of a patient with this rare disease.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can present with life-threatening lung-kidney syndromes. However, many controlled treatment trials excluded patients with diffuse alveolar hemorrhage or severely impaired glomerular filtration rates, and so the optimum treatment in these cases is unclear. In this retrospective cohort study, we report the outcomes of 64 patients with life-threatening disease treated with a combination regimen of rituximab, low-dose intravenous cyclophosphamide, oral glucocorticoids, and plasma exchange. At entry, the median estimated glomerular filtration rate was 9 mL/min, 47% of patients required dialysis, and 52% had diffuse alveolar hemorrhage. All patients received a minimum of seven plasma exchanges, and the median cumulative doses of rituximab, cyclophosphamide, and glucocorticoid were 2, 3, and 2.6 g, respectively, at six months. A total of 94% of patients had achieved disease remission (version 3 Birmingham Vasculitis Activity Score of 0) at this time point, and 67% of patients who required dialysis recovered independent kidney function. During long-term follow-up (median duration 46 months), overall patient survival was 85%, and 69% of patients remained free from end-stage kidney disease, which compares favorably to a historic cohort with severe disease treated with a conventional induction regimen. Combination treatment was associated with prolonged B cell depletion and low rates of relapse; 87% of patients were in continuous remission at month 36. The serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment is not associated with an enduring risk of infection. Thus, we suggest that combination immunosuppressive therapy may permit glucocorticoid avoidance and provide rapid and prolonged disease control in patients with severe ANCA-associated vasculitis.

Introduction: Sars-Cov-2 infection has been found to present differently in many patients. Patients have been found to have different degrees of response, likely having to do with variable levels of inflammation within the body. Patients who have recovered from the initial infection can develop long-term symptomatology and chronic conditions. Today, we will describe a unique case of a middle aged-healthy man who developed complications of ANCA-associated vasculitis after recovering from a mild COVID-19 infection. Case: A 51-year-old Hispanic male with no previous past medical history presented to the ED with productive sputum and hemoptysis. The patient had previously tested positive for COVID-19 one month prior, but did not require hospitalization. Physical exam findings were significant for diffuse, bilateral lower extremity palpable purpura. Initial workup was significant for CT Chest findings of diffuse patchy consolidations throughout both lungs with cavitary lesions. Additionally, the patient was found to have an acute kidney injury, with Cr 5.80 and GFR less than 10. UA revealed many red blood cells, +1 protein. Nephrology was consulted, started the patient on hemodialysis, and began workup for suspected acute glomerulonephritis (GN). Pulmonology was consulted and began workup for pulmonary renal syndrome in the setting of acute kidney injury with pulmonary disease.Infectious workup results included;a now negative COVID-19, negative Tuberculosis PCR, Respiratory culture revealing yeast. Additional workup revealed;CRP of greater than 200, D-Dimer of 6.41, Fibrinogen of 561. Notably, the patient had decreased complement C3 and C4 levels, negative Anti-GBM antibody, negative Anti-streptolysin O, positive ANCA assay, positive Proteinase antibody, and mildly positive Myeloperoxidase antibody.The patient was subsequently scheduled for renal biopsy to obtain a definitive diagnosis, but this was delayed due to increased INR. The patient's respiratory status worsened during hemodialysis. CTA at that time revealed markedly increased pulmonary infiltrates. The decision was made to intubate the patient, upon which active frank red bleeding arising from the trachea was noted. Shortly after intubation, the patient continued to hemorrhage and sustained 2 cardiac arrests;unfortunately, the patient expired. Discussion: This case is significant because it highlights a unique complication of COVID-19 leading to a possible ANCA-associated vasculitis. Much is to be learned from the Novel Sars-COV-2 virus and suspected complications and this case highlights the importance of keeping a broad differential when treating patients who have recovered from initial infection.

Oral isotretinoin is a synthetic analog of vitamin - A, reserved for cases with severe resistant acne. We hereby report a case of drug-induced vasculitis (DV) from isotretinoin exposure leading to life-threatening pulmonary-renal syndrome requiring immunosuppression and plasmapheresis. A previously healthy 21-year-old female receiving oral isotretinoin presented with a 10-day history of worsening myalgias, arthralgias, and abdominal pain. Soon after admission she progressed to severe pulmonary-renal syndrome requiring intubation and renal replacement therapy. Urinalysis revealed >50 dysmorphic RBC with casts and renal ultrasound was unremarkable. Serological testing was only positive for antineutrophil cytoplasmic antibodies (ANCA) at 1:80 with Anti- proteinase 3 (PR3) at 830 AU/mL and Anti-histone Ab at 2.9. As clinical presentation and serology are highly suggestive of ANCA associated DV, plasmapheresis, and rituximab were also initiated along with the continuation of steroids. She clinically improved but remained dialysis dependent and received a live donor renal transplant. The temporal relationship of symptom onset and drug initiation with no other possible identifiable etiologies-DV in our case was attributed to isotretinoin exposure. Though considered safe, oral Isotretinoin in rare instances can cause the life-threatening pulmonary-renal syndrome. Given its widespread use, it is prudent that prescribers should educate patients regarding the possible symptoms of vasculitis and to seek immediate medical attention when warranted. Physicians should also be vigilant of this complication and should act swiftly to avoid uneventful outcomes.

BackgroundAnti-glomerular basement membrane disease (GBM) disease is a rare autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary haemorrhage. Recently, an association between COVID-19 and anti-glomerular basement membrane (anti-GBM) disease has been proposed. We report on a patient with recurrence of anti-GBM disease after SARS-CoV-2 infection.Case presentationThe 31-year-old woman had a past medical history of anti-GBM disease, first diagnosed 11 years ago, and a first relapse 5 years ago. She was admitted with severe dyspnoea, haemoptysis, pulmonary infiltrates and acute on chronic kidney injury. A SARS-CoV-2 PCR was positive with a high cycle threshold. Anti-GBM autoantibodies were undetectable. A kidney biopsy revealed necrotising crescentic glomerulonephritis with linear deposits of IgG, IgM and C3 along the glomerular basement membrane, confirming a recurrence of anti-GBM disease. She was treated with steroids, plasma exchange and two doses of rituximab. Pulmonary disease resolved, but the patient remained dialysis-dependent. We propose that pulmonary involvement of COVID-19 caused exposure of alveolar basement membranes leading to the production of high avidity autoantibodies by long-lived plasma cells, resulting in severe pulmonary renal syndrome.ConclusionOur case supports the assumption of a possible association between COVID-19 and anti-GBM disease.

BACKGROUND: Pulmonary renal syndrome (PRS) is not a single entity but is caused by varied etiologies, including anti-neutrophil cytoplasmic antibody (ANCA), associated small vessel vasculitis (such as Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss vasculitis), Goodpasture’s syndrome, systemic lupus erythematosus, Henoch-Schonlein purpura, cryoglobulinemia, and rare causes such as druginduced vasculitis and subacute endocarditis. CASE REPORT: We report a case of a 51-year-old man who was referred to our hospital with a 2-month history of breathing difficulties, mild hemoptysis, and deteriorated renal function with a serum creatinine of 269 μmol/L. Serological testing was negative for anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) antibody, and also all cultures, including blood and urine, remained negative. In the renal biopsy, not linear deposition of IgG along the GBM and crescents at varying stages with extracapillary glomerulonephritis emphasizes the possibility of a double-seronegative pulmonary renal syndrome. Regarding therapeutic dilemmas, on the 3rd day of hospitalization, we initiated immunosuppression with cyclophosphamide and corticosteroids as well as plasma exchange (5 treatments). Under immunosuppressive therapy and plasma exchange, the patient’s status continually improved; there was no pulmonary bleeding, but the serum creatinine remained high and renal function remained in stage 4 chronic kidney disease. Four weeks later, he was hospitalized again, and we faced a new therapeutic dilemma because of the rapid relapse during immunosuppressive therapy and renal function deterioration that required hemodialysis treatment. Despite repeatedly negative results for anti-GBM and ANCA, initial immunosuppressive therapy with plasma exchange (9 treatments) was included again. The patient was discharged 30 days after admission in a stable general condition, with the maintenance immunosuppressive therapy with mycophenolate mofetil and hemodialysis 3 times/week. After 24 months, we have received information from the hemodialysis center that he is on regular hemodialysis and that he is in good condition. CONCLUSION: We think that in this atypical case, intensive plasma exchange and immunosuppressive therapy are crucial in the early stage and maintenance therapy is necessary for vasculitis in remission. This reported case has important clinical implications because pulmonary-renal syndrome with negative ANCAs and anti-GBM antibodies is extremely rare and no treatment recommendations have been established yet.

Description C3 glomerulonephritis (C3GN) is a rare disease that falls under the umbrella of C3 glomerulopathy (C3G). Classic manifestations of C3G include acute renal failure, proteinuria, and hematuria. In some cases, extrarenal manifestations can include ocular drusen. Until recent reports, C3G manifesting with pulmonary symptoms has not been reported. In this report, we describe a patient that initially presented with hemoptysis and acute renal failure, eventually leading to a diagnosis of pulmonary renal syndrome. Renal biopsy showed C3GN. The patient’s symptoms improved with pulse dose steroids, plasmapheresis and mycophenolate mofetil. C3G presenting with pulmonary symptoms is rare. Further research is needed to understand the mechanism of complement deposition in the lung parenchyma and to determine a standard therapy to treat these patients. Clinicians should be aware of the potential pulmonary manifestations that can be caused by C3GN.

Pulmonary syndrome is defined by occurrence of lung involvement (alveolar haemorrhage) in association with renal failure (with a typical crescentic necrotizing rapidly progressive glomerulonephritis). It is caused by an autoimmune disease, most frequently ANCA-associated vasculitides and anti-GBM (glomerular basement membrane) disease. Early establishment of the right diagnosis and immediate treatment are crucial for favourable prognosis of the patients. First choice therapy includes high-dose corticosteroids and cyclophosphamide, usually with plasma exchange added. Newer therapeutic possibilities include especially rituximab even though there is limited experience with its use in the settings of the most severe cases of pulmonary syndrome.

Background Antiglomerular basement membrane (anti-GBM) antibody disease is a rare condition causing pulmonary hemorrhage and necrotizing glomerulonephritis (pulmonary renal syndrome). Case We report a 30-year-old woman who presented with life-threatening pulmonary hemorrhage and an active urinary sediment, with normal glomerular filtration rate in the 13th week of pregnancy. Anti-GBM antibodies in serum were negative, but perinuclear antineutrophil cytoplasmatic antibodies (p-ANCA) were detected. A renal biopsy revealed necrotizing glomerulonephritis with linear IgG deposits along the glomerular basement membrane. A diagnosis of pulmonary renal syndrome caused by anti-GBM antibodies and p-ANCA (double-positive) was made. Plasma exchange was started but had to be changed to immunoadsorption because of an allergic reaction to fresh frozen plasma. Oral steroids were introduced. The patient also received one dose of intravenous cyclophosphamide followed by two 1-g doses of rituximab. The patient responded quickly to treatment with resolution of pulmonary hemorrhage and urinary abnormalities. The infant was delivered in the 38th week of pregnancy by caesarian section. It was small for age but otherwise completely healthy with a normal B-cell count. Conclusion To our knowledge, this is the first report of a double-positive pulmonary renal syndrome in pregnancy. Presentation in mid-pregnancy allowed for the application of cyclophosphamide without causing malformations and rituximab without B-cell depletion in the infant. .

C3 Glomerulopathy is a rare form of kidney disease due to dysregulation of the alternative complement pathway. We report a case of a college-aged woman with C3 glomerulonephritis (C3GN), presenting with the unexpected extrarenal manifestation of pulmonary hemorrhage. The patient presented with a nephritic urinary sediment and acute kidney injury after a recent infection. Kidney biopsy demonstrated focal endocapillary proliferative, crescentic, and necrotizing glomerulonephritis with bright glomerular C3 staining only. Electron microscopy revealed mesangial, intramembranous, and subendothelial deposits. After 2 doses of intravenous methylprednisolone, the patient developed spontaneous hemoptysis and respiratory compromise requiring emergent intubation. Bronchoscopy and computed tomography findings were consistent with diffuse alveolar hemorrhage. Notable laboratory results included C3, 40 (reference range, 75-175) mg/dL, and negative antinuclear antibody, antineutrophil cytoplasmic antibody, and anti–glomerular basement membrane serology results. As an outpatient, genetic testing revealed the presence of C3 glomerulopathy risk alleles. A diagnosis of C3GN complicated by pulmonary hemorrhage was made. There was initial response to treatment with steroids and mycophenolate mofetil; however, after repeated relapses of proteinuria and hematuria, treatment with eculizumab showed an initial response, but the patient subsequently became hemodialysis dependent. Our case highlights that C3GN can present with crescents and have other extrarenal manifestations such as pulmonary hemorrhage and should also be considered part of the differential diagnosis in patients presenting with pulmonary renal syndrome. Index Words: C3 Glomerulonephritis, pulmonary hemorrhage, complement pathway

Background Hydralazine is a common vasodilator which has been used for the treatment of hypertension and heart failure. Hydralazine can induce antineutrophil cytoplasmic antibody-associated vasculitis due to its auto-immunogenic capability and one of the very rare presentations is pulmonary–renal syndrome. Case presentation We report a case of a 64-year-old African American woman, who presented to our emergency room with shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, leg swelling, fatigue, loss of appetite, cough with clear sputum, and lightheadedness. On admission, she developed acute hypoxic respiratory failure requiring intubation and acute renal failure requiring hemodialysis. A serologic workup was positive for antineutrophil cytoplasmic antibody, antinuclear antibody, anti-histone, anti-cardiolipin IgM, and anti-double-stranded DNA antibodies. A renal biopsy was done due to persistent deterioration in kidney function and demonstrated classic crescentic (pauci-immune) glomerulonephritis. Hydralazine was empirically discontinued early in the admission and she was started on corticosteroids and cyclophosphamide following biopsy results. She was clinically stable but remained dependent on hemodialysis after discharge. Conclusion Hydralazine-induced antineutrophil cytoplasmic antibody-associated vasculitis with pulmonary–renal syndrome is a rare occurrence. In the setting of hydralazine use, multiple positive antigens, and multisystem involvement, clinicians should consider this rare condition requiring prompt cessation of offending drug, early evaluation with biopsy, and contemplate empiric immunosuppressive therapy while biopsy confirmation is pending.

A significant interaction between kidneys and lungs has been shown in physiological and pathological conditions. The two organs can both be targets of the same systemic disease (eg., some vasculitides). Moreover, loss of normal function of either of them can induce direct and indirect dysregulation of the other one. Subjects suffering from COPD may have systemic inflammation, hypoxemia, endothelial dysfunction, increased sympathetic activation and increased aortic stiffness. As well as the exposure to nicotine, all the foresaid factors can induce a microvascular damage, albuminuria, and a worsening of renal function. Renal failure in COPD can be unrecognized since elderly and frail patients may have normal serum creatinine concentration. Lungs and kidneys participate in maintaining the acid-base balance. Compensatory role of the lungs rapidly expresses through an increase or reduction of ventilation. Renal compensation usually requires a few days as it is achieved through changes in bicarbonate reabsorption. Chronic kidney disease and end-stage renal diseases increase the risk of pneumonia. Vaccination against Streptococcus pneumonia and seasonal influenza is recommended for these patients. Vaccines against the last very virulent H1N1 influenza A strain are also available and effective. Acute lung injury and acute kidney injury are frequent complications in critical illnesses, associated with high morbidity and mortality. The concomitant failure of kidneys and lungs implies a multidisciplinary approach, both in terms of diagnostic processes and therapeutic management.

Immunoglobulin A (Ig A) nephropathy is the most frequent primary glomerulonephritis. Renal limited disease is the most widespread clinical form of the disease. Pulmonary involvement may also be seen concomitantly and capillaritis with pulmonary hemorrhage is the most frequent pulmonary involvement. In this paper, for the first time in literature, we describe an Ig A nephropathy patient with multiple pulmonary cavities as one of the presenting features of the disease. Also, no other etiology for the cavities was found other than Ig A nephropathy. Herein, possible pathogenesis might be capillaritis or deposition of immune complexes. As a result, it should be kept in mind that pulmonary cavity may be the presenting feature of Ig A nephropathy especially with other frequent signs of the disease.

Goodpasture's syndrome is a triad of anti-glomerular basement membrane (anti-GBM) circulating antibodies, glomerulonephritis and pulmonary hemorrhage. We reported a 65-year-old woman with headaches, asthenia and weight loss. Giant cell arteritis was confirmed by temporal artery biopsy. The patient had associated renal condition with moderate acute renal failure, proteinuria and haematuria. Renal biopsy showed extracapillary glomerulonephritis and linear staining of immunoglobulins G along glomerular basement membrane. There was no clinical pulmonary involvement. Anti-MBG antibody was positive and allowed Goodpasture's syndrome diagnosis. The patient was treated with corticoids and cyclophosphamide. Patient's condition and renal function improved quickly and anti-MBG antibodies became negative. Goodpasture's syndrome may be characterized by isolated renal expression without pulmonary involvement. We described for the first time association of Goodpasture's syndrome with giant cell arteritis.

Scleroderma associated Pulmonary–Renal Syndrome is a rare but severe complication with a poor prognosis and high mortality. A high index of suspicion is needed for early recognition of this potential complication in patients with systemic sclerosis and institution of appropriate treatment. With more data showing an increased association between scleroderma and malignancy, a heightened vigilance should also be exercised in patients with malignancy and scleroderma-like presentation. We report of a case rapid onset systemic sclerosis complicated by acute renal failure and diffuse alveolar hemorrhage in a woman with stage IIB right breast cancer and elevated RNA Polymerase III IgG Ab. To our knowledge, this the first case of a patient with breast cancer associated with systemic sclerosis and pulmonary-renal syndrome. Keywords: Systemic sclerosis, Pulmonary-renal syndrome, Scleroderma renal crisis, Diffuse alveolar hemorrhage, Breast cancer, Positive anti-RNA polymerase III Ab, Pleural effusion, Pericardial effusion

Pulmonary renal syndrome (PRS) is a high mortality, rare disorder presenting with diffuse alveolar hemorrhage and progressive acute glomerulonephritis. This syndrome is often caused by autoimmune entities, the most frequent being ANCA positive vasculitis and anti-GBM disease. We report a case of a 34-year-old Chilean woman, who initially presents with anemia and after a few days of inpatient management, starts with progressively worsening dyspnea, decrease in renal function and hematuria. The patient is initially diagnosed with pneumonia, but further evaluation using Thorax CT scan and renal biopsy confirms the suspicion of PRS. The case is of particular interest due to the lack of extensive bibliography on anti-GBM and ANCA negative pulmonary-renal syndrome, an uncategorized subtype of this syndrome with unknown optimal management.

Key Clinical Message Hemophagocytosis Lymphocytosis (HLH) is a rare and life‐threatening illness that is more commonly seen in infants; however, its incidence in adults is becoming more common. Recognizing HLH in a complicated clinical scenario is key to early recognition, treatment, as well as improved morbidity and mortality.

Antineutrophil cytoplasmic antibody (ANCA) has been known to cause pauci-immune crescentic glomerulonephritis. In addition, several reports described membranous glomerulonephritis (MN) concurrent with ANCA-associated glomerulonephritis. Because the two glomerular diseases simultaneously appear in an ANCA-positive patient, the mechanisms whereby ANCA causes the two different glomerular diseases remain ambiguous. Herein, we report a case of 19-year-old man who presented with hematuria, pre-nephrotic proteinuria, and high titer of myeloperoxidase (MPO)-ANCA. The first renal biopsy revealed MN with chronic glomerular scar lesions of unknown etiology. Predominant immunoglobulin (Ig) G1 subclass and negative phospholipase-A2 receptor staining, together with granular-positive glomerular capillary co-localization of MPO and IgG staining, suggested secondary MN due to MPO-MPO-ANCA immune-complex. Five years later, the patient presented with fever, severe renal dysfunction, and alveolar hemorrhage with high titer of MPO-ANCA that indicated pulmonary renal syndrome due to ANCA-associated vasculitis. The second renal biopsy revealed pauci-immune crescentic glomerulonephritis without either apparent MN-lesion or glomerular IgG staining. This is the first reported case showing that MPO-ANCA caused two different glomerular diseases, MN and pauci-immune crescentic glomerulonephritis, in the same patient at the different time points. Our case indicated that common MPO-ANCA might cause different glomerular diseases by different immune mechanisms.

Pulmonary renal syndrome refers to an association of pulmonary and glomerular disease and includes disorders, such as the ANCA-associated vasculitides, anti-glomerular basement membrane antibody disease, systemic lupus erythematosus, and IgA vasculitis (Henoch-Schönlein purpura). We present the medical history of a 26-month-old boy with an extensive purpuric rash, involving the limbs, trunk, and face, who developed clinically significant pulmonary hemorrhage and renal involvement. Rapid recognition of this rare but potentially life-threatening condition is crucial. In this report, we discuss the differential diagnosis, diagnostic studies, and treatment options to consider when facing a young child presenting with a pulmonary renal syndrome.

This article aims to report a case of a young female patient with anti-neutrophil cytoplasmic antibodies-associated vasculitis complicated with pulmonary renal syndrome, multiple relapses, and who later developed venous thromboembolism. Pulmonary renal syndrome is a well- recognized and lethal complication; however, incidence of venous thromboembolism has not been well-described. In this article, we described a 38-year-old Malay female patient admitted in 2008 with three-month history of peripheral neuropathy of lower limbs and right ankle ulcers. Initial inflammatory markers were high and perinuclear Anti-Neutrophil Cytoplasmic Antibodies were positive. She was diagnosed as anti-neutrophil cytoplasmic antibodies-associated vasculitis and started on intravenous methylprednisolone with methotrexate. She presented with relapse of skin vasculitis complicated with pulmonary renal syndrome after being stable for one year. She was intubated and proceeded with plasmapheresis and hemodialysis. She completed six cycles of cyclophosphamide. Renal biopsy revealed chronic changes consistent with end stage renal disease. She further relapsed in 2011 with nasal blockage, epistaxis, and nasal deviation. Chest X-ray revealed lung nodules. Prednisolone was increased, her symptoms settled, and she was discharged with azathioprine. She was readmitted at the end of the same year due to two-day history of right deep vein thrombosis and she later succumbed to methicillin-resistant Staphylococcus aureus sepsis.

The etiology of pulmonary renal syndrome can be broadly divided into infectious and autoimmune (predominantly ANCA vasculitis). The importance of timely differentiating between them stems from the deleterious effects of their respective treatment if misdiagnosed. Serology and tissue evaluation by pathology are employed to aid in this, however, in rare cases, this can be difficult. We present a case of infectious endocarditis that presented with pulmonary renal syndrome but had positive ANCA serology and a pauci-immune glomerulonephritis picture on kidney biopsy that posed diagnostic difficulty. Factors most helpful in differentiating between the two conditions are highlighted as well as treatment options. .