Systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis overlap syndrome in a 77-year-old man: A case report

BACKGROUNDSystemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are classically thought to cause renal impairment and small vessel vasculitis with different pathophysiologies. Their overlap constitutes a rare rheumatologic disease. To date, only dozens of such cases with biopsy-proven glomerulonephritis have been reported worldwide typically in women of childbearing age. Here, we present a unique clinical case due to its rarity and individualized treatment of a Chinese man in his eighth decade of life.CASE SUMMARYA 77-year-old man was admitted to several hospitals for shortness of breath and received nonspecific treatments over the past 3 years. As his symptoms were not completely relieved, he visited our hospital for further treatment. Laboratory examinations revealed kidney dysfunction, severe anaemia, hypocom-plementemia, glomerular proteinuria, and microscopic haematuria. Antinuclear antibodies, as well as anti-dsDNA antibodies, were positive. Computed tomography of the chest showed right pleural effusion. Renal biopsy was performed, and histology suggested crescentic glomerulonephritis, pauci-immune type. After treatment with plasmapheresis, glucocorticoid, and cyclo-phosphamide, the disease was in remission, and the patient remained in a stable condition for over 3 years post-hospital discharge.CONCLUSIONDue to its complexity and rarity, SLE and AAV overlap syndrome is easily misdiagnosed. An accurate diagnosis and treatment at the earliest stage may significantly improve the condition and reduce irreversible organ injury.     

抗中性粒细胞胞质抗体相关性血管炎心脏受累影像学所见

抗中性粒细胞胞质抗体(ANCA)相关性血管炎(AAV)为全身坏死性小血管炎,可累及全身多个器官,肾脏和肺最常受累,心脏受累则相对少见,但多与预后不良相关.本文对AAV累及心脏的机制及其常见心电图、超声心动图及心脏M RI表现进行综述.     

ANCA相关性血管炎肾损害合并交通性脑积水一例并文献复习

目的 探讨合并交通性脑积水的ANCA相关性血管炎（AAV）的发病机制、诊治方法,提高临床医师对AAV罕见类型的认识水平。方法 收集1例以交通性脑积水为首发症状的AAV病例的临床资料,以“ANCA相关性血管炎”“脑积水”为关键词（包括中英文）对PubMed和CNKI收录的论文进行检索,结合文献分析病例特点、实验室检查、影像学检查、肾脏活组织检查（活检）和诊治方法。结果 该例71岁男性患者,因头晕伴行走不稳半年余在门诊行CT检查提示交通性脑积水,拟行手术治疗。术前检查发现血清肌酐635 μmol/L,核周型-抗中性粒细胞胞质抗体（p-ANCA）（+）,MPO 293 U/L,尿红细胞位相示畸形红细胞240 000 /μL,经肾脏活组织检查（活检）证实存在AAV肾损害。随访30个月,经糖皮质激素（激素）联合环磷酰胺治疗后,患者血清肌酐降至335 μmol/L并脱离透析,头晕、行走不稳、智力减退症状逐渐好转,后多次复查颅脑MRI,交通性脑积水较前无明显变化。检索数据库后共收集5篇相关病例报道,患者年龄33~76岁,临床表现为脑积水和AAV,予激素联合免疫抑制剂、脑室-腹膜分流术等治疗,随访期间1例患者死亡,另外4例患者症状缓解。结论 以脑积水起病的AAV罕见且血管炎症状隐匿,易被误诊或漏诊,对不明原因伴肾衰竭的神经系统受累病变进行ANCA筛查十分必要,肾穿刺活检有助于明确诊断,及时正规治疗可缓解脑积水症状,有助改善患者预后。     

Activated phosphoinositide 3-kinase delta syndrome misdiagnosed as anti-neutrophil cytoplasmic antibody-associated vasculitis: a case report

Activated phosphoinositide 3-kinase delta syndrome (APDS) is a combined inborn error of immunity mainly caused by PIK3CD mutations. We herein describe a 4-year-old Chinese boy who was admitted for recurrent pneumonia and persistent hematuria and exhibited multisystem involvement and anti-neutrophil cytoplasmic antibody (ANCA) positivity. He was initially diagnosed with ANCA-associated vasculitis. However, genetic testing revealed a c.1574A>G PIK3CD mutation, resulting in a diagnosis of APDS1.     

Serum progranulin as a predictive marker for high activity of antineutrophil cytoplasmic antibody‐associated vasculitis

BackgroundThis study investigated whether serum progranulin could act as a predictive marker for high disease activity of antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV).MethodsFifty‐eight AAV patients were included in this study. Clinical and laboratory data were obtained at blood collection. The Short‐Form 36‐Item Health Survey Physical and Mental Component Summaries (SF‐36 PCS and SF‐36 MCS), Birmingham Vasculitis activity score (BVAS), Five‐Factor Score (FFS), and Vasculitis Damage Index (VDI) were assessed as AAV‐specific indices. Whole blood was collected and serum samples were isolated and stored at −80°C. Serum progranulin concentration was quantified by ELISA kits.ResultsThe median age of patients was 63.0 years (19 men). The median BVAS was 11.0, and the median serum progranulin level was 49.0 ng/ml. Serum progranulin was significantly correlated with BVAS, FFS, erythrocyte sedimentation rate, C‐reactive protein level, SF‐36 PCS, haemoglobin, and serum albumin. Severe AAV was arbitrarily defined as the highest tertile of BVAS (BVAS ≥16). When the cut‐offs of serum progranulin were set as 55.16 ng/ml and 43.01 ng/ml for severe AAV, AAV patients with serum progranulin ≥55.16 and 43.01 ng/ml had significantly higher risks of severe AAV than those without (relative risk (RR) 4.167 and 4.524, respectively).ConclusionsProgranulin might play an anti‐inflammatory role in AAV pathogenesis and serum progranulin could be used as a predictive marker for high activity of AAV.     

Oral cyclophosphamide-induced posterior reversible encephalopathy syndrome in a patient with ANCA-associated vasculitis: A case report

BACKGROUNDPosterior reversible encephalopathy syndrome (PRES) manifests many neurological symptoms with typical features on neuroimaging studies and has various risk factors. Cyclophosphamide is one of the therapeutic agents for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Cyclophosphamide as the sole cause of PRES has been reported in only a few cases. Herein, we report a unique case of early-onset oral cyclophosphamide-induced PRES in a patient with ANCA-associated vasculitis. CASE SUMMARYA 73-year-old man was transferred to our hospital for sepsis due to acute cholangitis. He had already received hemodialysis for two weeks due to septic acute kidney injury. His azotemia was not improved after sepsis resolved and perinuclear-ANCA was positive. Kidney biopsy showed crescentic glomerulonephritis. Alveolar hemorrhage was observed on bronchoscopy. He was initially treated with intravenous methylprednisolone and plasma exchange for one week. And then, two days after adding oral cyclophosphamide, the patient developed generalized tonic-clonic seizures. We diagnosed PRES by Brain magnetic resonance imaging (MRI) and electroencephalography. Seizures were controlled with fosphenytoin 750 mg. Cyclophosphamide was suspected to be the cause of PRES and withdrawal. His mentality was recovered after seven days and brain MRI showed normal state after two weeks. CONCLUSIONThe present case shows the possibility of PRES induction due to short-term use of oral cyclophosphamide therapy. Physicians should carefully monitor neurologic symptoms after oral cyclophosphamide administration in elderly patients with underlying diseases like sepsis, renal failure and ANCA-associated vasculitis.     

The confused puzzles in antineutrophil cytoplasmic antibody‐associated vasculitis activity evaluation: A case report

Antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is a group of chronic multisystem autoimmune diseases with substantial mortality and morbidity and frequent relapses. The complexity of the disease condition and treatment‐related adverse reactions as well as infections play important roles in the poor outcomes. Unfortunately, the subjective symptoms and objective indicators are not fully parallel, and manifestations between disease activity and treatment‐related adverse reactions are often similar. Here, we describe a case of pulmonary mucormycosis in an old female patient with AAV to highlight these challenges.     

Associations between ATG16L1 gene polymorphism and antineutrophil cytoplasmic antibody‐associated vasculitis in the Chinese Guangxi population: A case–control study

BackgroundAntineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is an autoimmune disease often accompanied by rapidly progressive renal failure, and the genetic background is still unknown. Our study was performed to test whether autophagy‐related 16 like 1 (ATG16L1) rs4663402 and rs4663396 single nucleotide polymorphisms (SNPs) were associated with AAV in the Chinese Guangxi population.MethodsOne hundred seventy seven unrelated AAV patients and 216 healthy controls were included in this case–control study. Multiplex polymerase chain reaction combined with high‐throughput sequencing was used for typing, and SNPStats and SHEsis were used for association analysis, pairwise linkage disequilibrium, and haplotype analysis.Resultsrs4663402 and rs4663396 were in Hardy–Weinberg equilibrium in AAV and control groups. The frequencies of rs4663402 AA, AT, and TT genotypes were 82.5%, 16.9%, and 0.6%, respectively, in patients with AAV, and 83.5%, 16.2%, and 0.5%, respectively, in controls. The frequencies of rs4663396 CC, CT, and TT genotypes were 63.8%, 33.9%, and 2.3%, respectively, in patients with AAV, and 69.2%, 26.6%, and 4.2%, respectively, in controls. Haplotype analysis revealed two SNPs in a single haplotype block (D′ = 1.0). Our logistic regression adjusted for sex and age showed no association between rs4663402 and rs4663396 and the risk for AAV in genetic models (p > 0.05). However, ATG16L1 rs4663396 CC and CT + TT genotypes exhibited statistically significant differences in the incidence of arthralgia (p = 0.03).ConclusionsOur results indicated that ATG16L1 rs4663402 and rs4663396 polymorphisms were not associated with AAV in the Chinese Guangxi population. ATG16L1 rs4663396 CT + TT genotype may be associated with arthralgia.     

Eosinophilic granulomatosis with polyangiitis presenting with repetitive acute coronary syndrome,refractory coronary vasospasm,and spontaneous coronary dissection: a case report

Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of eosinophilic vasculitis that is mainly limited to small- and medium-sized arteries. Cardiac involvement is the leading cause of death in patients with EGPA. Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome in middle-aged women with no or few traditional cardiovascular risk factors. EGPA manifesting as repetitive acute coronary syndrome and SCAD has not been reported. A 45-year-old woman presented with recurrent chest pain and cardiogenic shock associated with coronary vasospasm refractory to common vasodilators. Coronary angiography showed SCAD at the proximal right coronary artery. Blood tests showed significant eosinophilia. In addition to sinusitis as shown by nasal computed tomography and abnormal nerve conduction velocity, the diagnosis of EGPA was made and immunosuppression commenced. During a 20-month follow-up, the patient remained free from symptoms and adverse cardiovascular events. EGPA can involve coronary arteries and may rarely manifest as SCAD or vasospasm. We herein review the mechanism underlying coronary involvement of EGPA and emphasize special clues for its detection. Early recognition and initiation of immunosuppression therapy are important.     

Analysis of rs1864182 and rs1864183 variants in ATG10 gene and antineutrophil cytoplasmic autoantibody‐associated vasculitis in Chinese Guangxi population

ObjectivesTo investigate the association of autophagy‐associated gene 10 (ATG10) gene polymorphisms (rs1864182 and rs1864183) with antineutrophil cytoplasmic autoantibody (ANCA)‐associated vasculitis (AAV) in Chinese Guangxi population.MethodsThe single nucleotide polymorphisms (SNPs) of ATG10 rs1864182 and rs1864183 in 395 participants (195 AAVs and 200 healthy controls) were genotyped. Generalized multiple dimensionality reduction (GMDR) was used to analyze the SNP‐SNP interactions among two SNPs of ATG10 gene and other SNPs of autophagy gene previously studied by our research team.ResultsIn this study, we found that the two ATG10 SNPs were not associated with AAV risk in Chinese Guangxi population. However, there were statistically significant differences in the incidence of hemoptysis, hematuria, and proteinuria among the three genotypes of ATG10 rs1864182 and rs1864183 (p < 0.05). Moreover, permutation test of GMDR suggested that immunity‐related GTPase M(IRGM) rs4958847, autophagy‐associated gene 7 (ATG7) rs6442260, ATG7 rs2594966, ATG10 rs1864183, protein kinase B(AKT2) rs3730051, and AKT2 rs11552192 might interact with each other in the process of developing AAV (p < 0.05).ConclusionsOur results indicated that there existed no association between ATG10 SNPs and AAV, and SNP‐SNP interactions among IRGM rs4958847, ATG7 rs6442260, ATG7 rs2594966, ATG10 rs1864183, AKT2 rs3730051, and AKT2 rs11552192 may confer AAV risk in the Chinese Guangxi population.     

Acute myocardial infarction induced by eosinophilic granulomatosis with polyangiitis: A case report

BACKGROUNDEosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem disease characterized by allergic rhinitis, asthma, and a significantly high eosinophil count in the peripheral blood. It mainly involves the arterioles and venules. When the coronary arteries are invaded, it can lead to acute myocardial infarction (AMI), acute heart failure, and other manifestations that often lead to death in the absence of timely treatment.CASE SUMMARYA 69-year-old man was admitted to the emergency department due to chest pain for more than 1 h. He had a past history of bronchial asthma and chronic obstructive pulmonary disease and was diagnosed with AMI and heart failure. Thrombus aspiration of the left circumflex artery and percutaneous transluminal coronary angioplasty were performed immediately. After surgery, the patient was admitted to the intensive care unit. The patient developed eosinophilia, and medical history taking revealed fatigue of both thighs 1 mo prior. Local skin numbness and manifestations of peripheral nerve involvement were found on the lateral side of the right thigh. Skin biopsy of the lower limbs pathologically confirmed EGPA. The patient was treated with methylprednisolone combined with intravenous immunoglobulin and was discharged after 21 d. On follow-up at 7 d after discharge, heart failure recurred. The condition improved after cardiotonic and diuretic treatment, and the patient was discharged.CONCLUSIONAsthma, impaired cardiac function, and eosinophilia are indicative of EGPA. Delayed diagnosis often leads to heart involvement and death.     

A novel GHR-ALK fusion gene in a patient with metastatic lung adenocarcinoma and its response to crizotinib: a case report

Anaplastic lymphoma kinase (ALK) rearrangement occurs in approximately 5% of non-small cell lung cancers (NSCLCS), and EML4-ALK is the most commonly observed ALK fusion variant in NSCLC. However, growth hormone receptor (GHR) as the fusion partner for ALK and the clinical response to ALK tyrosine kinase inhibitors in patients with metastatic lung adenocarcinoma (LUAD) who carry the GHR-ALK variant have not been documented. This case describes a 63-year-old woman diagnosed with metastatic LUAD. Immunohistochemistry revealed positive ALK expression, and the patient was treated with crizotinib. After 3 weeks of treatment, the patient had a partial response. Because of treatment-related adverse events, the dose of crizotinib was reduced. After 3.7 months, computed tomography uncovered disease progression. Next-generation sequencing identified a novel GHR-ALK fusion in the plasma of the patient. The patient was treated again with crizotinib, but the disease progressed again 2 months later. Then, the patient received chemotherapy. She succumbed to her disease 11 months after the initial diagnosis. Our work provides evidence supporting the use of crizotinib in patients with metastatic LUAD harboring GHR-ALK.     

Unusual presentation of granulomatosis with polyangiitis causing periaortitis and consequent subclavian steal syndrome: A case report

BACKGROUNDGranulomatosis with polyangiitis (GPA) is a rare autoimmune disease that involves small-to-medium-sized vessels and forms necrotizing vasculitis with granulomatous inflammation. The formation of a large vessel lesion in GPA patients has been scarcely reported, and it can cause confusion in the diagnosis. CASE SUMMARYA 27-year-old man presented with mild left-sided pleuritic chest pain that started one year prior. An imaging study revealed up to 2.5 cm-sized two irregular nodular consolidation nodule in the left lower lobe. Both nodules showed central necrosis. Also, there was a periaortic mass occluding the branching porting of the subclavian artery. He had positive anti-neutrophil cytoplasmic antibodies (ANCAs), but myeloperoxidase-ANCAs and proteinase 3-ANCAs were negative. The patient also developed symptoms of subclavian vein syndrome during the follow-up. Wedge resection of the lung revealed necrotizing vasculitis, destructive parenchymal abscess and surrounding granuloma, and therefore diagnosed of GPA. The patient started on methotrexate and steroid therapy with a relief of symptomatic.CONCLUSIONHere, we present an unusual manifestation of GPA with periaortitis and consequent subclavian steal syndrome, which has never been previously described. This case alerts us that we should include GPA in the differential diagnosis of large vessel vasculitis as well as subclavian steal syndrome.     

Histology transformation-mediated pathological atypism in small-cell lung cancer within the presence of chemotherapy: A case report

BACKGROUNDThe treatment of small-cell lung cancer (SCLC) has progressed little in recent years because of its unique biological activities and complex genomic alterations. Chemotherapy combined with radiotherapy has been widely accepted as the first-line treatment for SCLC.CASE SUMMARYHere, we present a 68-year-old male smoker who was diagnosed with SCLC of the right lung. After several cycles of concurrent chemoradiotherapy, the tumor progressed with broad metastasis to liver and bone. Histopathological examination showed an obvious transformation to adenocarcinoma, probably a partial recurrence mediated by the chemotherapy-based regimen. A mixed tumor as the primary lesion and transformation from SCLC or/and tumor stem cells may have accounted for the pathology conversion. We adjusted the treatment schedule in accord with the change in phenotype.CONCLUSIONAlthough diffuse skeletal and hepatic metastases were seen on a recent computed tomography scan, the patient is alive, with intervals of progression and shrinkage of his cancer.     

Recurrent paroxysmal cold haemoglobinuria in a 3-year-old child: a case report

We present the case of a 3-year-old girl who presented on two separate occasions, eight months apart, with typical features of paroxysmal cold haemoglobinuria (PCH). On each occasion, she suffered malaise and fever with dark urine following an upper respiratory tract infection. She developed severe anaemia and required transfusion of red cells on both occasions, although each time she made a quick recovery. She was found to be direct antiglobulin test-positive with anti-C3d, and agglutination was observed on the blood film. A biphasic Donath-Landsteiner antibody was demonstrated. The specificity of the antibody was not identified, although it was not anti-P. As far as we are aware, recurrence of acute PCH in a child has not been previously reported in the literature.     

Paraneoplastic immunoglobulin A nephropathy in a patient with lung adenocarcinoma: A case report and literature review

Immunoglobulin A nephropathy (lgAN) is a common primary glomerulonephritis, but paraneoplastic IgAN has been rarely reported. This current case report describes a 49-year-old male patient that was referred with proteinuria, oedema and hypoproteinaemia after lung cancer surgery and before the first cycle of chemotherapy. Renal biopsy confirmed lgAN. The patient received four cycles of chemotherapy (first cycle: pemetrexed + nedaplatin; second to fourth cycle: pemetrexed + carboplatin). The symptoms of IgAN were gradually relieved with additional cycles of chemotherapy. At the latest follow-up on 10 February 2020, there was no evidence of lung cancer recurrence and all symptoms of lgAN had disappeared. lgAN combined with lung adenocarcinoma is quite rare, which suggests that IgAN might be a paraneoplastic manifestation of lung adenocarcinoma.     

Eye metastasis in lung adenocarcinoma mimicking anterior scleritis:A case report

BACKGROUND The eye is a rare site for lung cancer metastasis. Indeed, ocular metastasis is one of the greatest challenges to quality of life in a cancer patient. Here we present a patient with lung adenocarcinoma and ocular metastasis.CASE SUMMARY The patient was a 70-year-old man diagnosed with lung adenocarcinoma who developed eye metastasis mimicking anterior scleritis. Brain magnetic resonance imaging showed an abnormal signal in the right eye. Based on next generation sequencing of the surgical specimen, the patient was shown to have a KRAS point mutation(p.G12D).CONCLUSION Multidiscipline expertise collaboration is needed to make the early diagnosis and determine the prompt treatment in patients. We hope to increase the awareness of the possibility of lung cancer metastasizing to the eye.