Systemic Lupus Erythematosus (SLE) and Antineutrophil ... Case Report Systemic Lupus Erythematosus
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Case ReportSystemic Lupus Erythematosus (SLE) and AntineutrophilCytoplasmic Antibody-Associated Vasculitis (AAV) OverlapSyndrome: Case Report and Review of the Literature
Sathish Itikyala, Debendra Pattanaik , and Syed Raza
University of Tennessee Health Science Center, Division of Rheumatology, Memphis, TN, USA
Correspondence should be addressed to Debendra Pattanaik; email@example.com
Received 24 September 2018; Revised 2 December 2018; Accepted 12 December 2018; Published 6 January 2019
Academic Editor: Jamal Mikdashi
Copyright 2019 Sathish Itikyala et al.*is is an open access article distributed under theCreative CommonsAttribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
We report here the first case of systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitisoverlap syndrome (SLE/AAV) who had granulomatous polyangiitis (GPA) as the initial presentation. SLE/AAV overlap syn-drome is an uncommon entity recently described in the literature. Prior reported patients with SLE/AAV overlap syndromepresented with SLE and microscopic polyangiitis (MPA). Our patient initially presented with granulomatous gastric ulcer andlater developed respiratory failure. She was diagnosed with GPA. While on maintenance treatment with azathioprine 150mg/day,she developed hematuria and proteinuria which turned out to be from class V lupus nephritis instead of relapse of vasculitis.Currently, the patient is doing well after treatment with rituximab. Although rare, this entity should be recognized and need to betreated appropriately.
Systemic lupus erythematosus (SLE) is a multisystem au-toimmune disease characterized by the presence of auto-antibodies and heterogeneous clinical presentation .Antineutrophil cytoplasmic antibody- (ANCA)-associatedvasculitis (AAV) on the other hand is a necrotizing vasculitisinvolving small to medium vessels and presence of anti-neutrophil cytoplasmic antibodies (ANCAs) specific foreither myeloperoxidase (MPO) or proteinase 3 (PR3) .AAV includes three major clinicopathologic variants:granulomatosis with polyangiitis (GPA, Wegeners gran-ulomatosis), microscopic polyangiitis (MPA), and eosino-philic granulomatosis with polyangiitis (EGPA,ChurgStrauss syndrome). *e prevalence of ANCAs isreported to be as high as 31% in lupus patients but its role inSLE has no demonstrable clinical significance . SLE/AAVoverlap syndrome is a recently described entity wheresubjects had SLE and microscopic polyangiitis with rapidlydeveloping glomerulonephritis [4, 5]. Majority of the pa-tients were diagnosed concomitantly with SLE and AAV .
Ninety-two percent of the reported cases presented withserious manifestations, e.g., rapidly progressive glomeru-lonephritis, and were treated aggressively with cortico-steroids and cyclophosphamide . Other commonorgan-threatening manifestations reported include CNSvasculitis and thrombotic cerebrovascular events . *ir-teen percent of the reported cases died of complications .Our patient initially presented with PR3 positive AAV withinvolvement of the GI tract and lungs who eventually de-veloped class V lupus nephritis. All the previously reportedcases of SLE/AAV syndrome had AAV with + P-ANCA andMPO antibody, and most common renal manifestation wasrapidly progressive glomerulonephritis unlike our case.
2. Case Presentation
A 48 -year-old Indian woman presented to the gastroen-terology clinic with complaints of upper abdominal pain,heartburn, and unintentional 10-pound weight loss over aperiod of 6months. Review of the system was negative for
HindawiCase Reports in RheumatologyVolume 2019, Article ID 5013904, 5 pageshttps://doi.org/10.1155/2019/5013904
headache, nasal discharge, cough, chest pain, shortness ofbreath, sinusitis, joint pain, or skin rash. Past medical historyis notable for hypothyroidism only. Family history andpersonal history is otherwise unremarkable. Her medicationsinclude levothyroxine 50 mcg daily. She underwent EGD,which revealed a solitary 1.4 cm ulcer in the gastric fundus.Biopsy of the ulcer revealed active chronic gastritis withlymphoid aggregates and nonnecrotizing granulomatousinflammation with multinucleated giant cells (Figure 1).
Histochemical staining and culture results were negativefor any bacterial, viral, and fungal infections. *e biopsy wasnegative for gastric carcinoma. She was then empiricallytreated with proton pump inhibitors. Two months later, thepatient presented to emergency room with cough, pleuriticchest pain, and hemoptysis. *e CT chest showed two largenecrotic masses (Figure 2): one in the right upper lobe with acavitary lesion and the other in the mediastinum.
She eventually underwent elective bronchoscopy withtransbronchial biopsies and bronchoalveolar lavage (BAL).Right upper lobe transbronchial biopsy showed bronchialmucosa with acute and chronic inflammation (lymphocytes,neutrophils, eosinophils, and rare histiocytes) and smallsubmucosal microabscess. Lung alveolar parenchyma waswithout significant histopathological changes. *e biopsywas negative for any form of lung malignancy. *e BAL wasnegative for pulmonary hemorrhage. No fungi, pneumo-cystis, or viral inclusion bodies were identified in BAL.Bacterial and fungal and mycobacterial cultures of BAL werenegative as well. Infectious disease workup showed positivehistoplasma serum antibody but histoplasma urine antigenwas negative. Presumed diagnosis of histoplasmosis wasmade, and she was started on oral itraconazole as outpatienttherapy. *e patient did not respond well, and her clinicalstatus continued to decline. She then presented to theemergency room with spiking fevers and recurrence ofhemoptysis. She was admitted to the inpatient service andstarted on IV amphotericin-B per infectious disease servicerecommendations. During hospitalization, she complainedof epigastric discomfort. CT abdomen showed opacityaround the previously found gastric ulcer and fluid col-lection adjacent to the stomach and pancreatic bed. RepeatEGD showed further development of a sinus tract in theulcer, leaking exudate, and necrotic debris. Biopsies of theulcer again showedmild active chronic gastritis. No evidenceof infection or malignancy was identified. During thehospital course, she developed arthralgia and maculopapularpruritic skin lesions on the right flank and both legs. After aweek into the hospitalization, the patient developed severeshortness of breath and acute respiratory failure that re-quired intubation and mechanical ventilation. CT chestrevealed worsening of the previous right upper lobe cavitarylesion with pleural effusion. Skin biopsy showed leukocy-toclastic vasculitis. Further workup showed positive ANA inthe low titer (1 : 40, homogenous pattern). Specific anti-bodies, e.g., anti-dsDNA, anti-Smith ab, anti-SSA and SS-B,were negative. Complements, C3: 113 (90180mg/dl) andC4: 12 (1040mg/dl), were within normal limits. *eC-reactive protein level was 86mg/dl (normal< 0.5mg/dl).Serum protein electrophoresis showed polyclonal acute
phase reactant pattern. C-ANCA was positive with positivePR3: 7.21 (0.81.19AU/mL). Anti-MPO antibody wasnegative. At this point, the diagnosis of GPAwas established.
She was treated with pulse methylprednisolone 1 g IVdaily for 3 days and IV cyclophosphamide 750mg/m2.During hospitalization, she received a course ofsulfamethoxazole-trimethoprim (800160mg DS) tab POtwice daily for 5 days for urinary tract infection. Sheresponded very well and was promptly extubated and dis-charged in two weeks. She was maintained on PO predni-sone 1mg/kg/day and IV cyclophosphamide 750mg/m2monthly for the next 6months. At 3months post-hospitaldischarge follow-up, she was completely asymptomatic.Repeat anti-PR3 titer was 3.6 (normal 0.81.19AU/mL).*ere was a near-complete resolution of pulmonarymasses on repeat CT (Figure 3) and complete healing of theulcer on follow-up EGD.
Prednisone was tapered to 10mg/d over 6 months whileshe received monthly IV cyclophosphamide inductiontherapy. *e PR3 antibody level was 1.0 and within normallimits. She was eventually started on PO methotrexate15mg/week as maintenance therapy for GPA.While she wason methotrexate, 6 months follow-up CT chest showedrelapse of the necrotic lung lesions at the same place asbefore in the right upper lobe. *e ANCA (PR-3) antibodylevel was 2.8 (normal 0.81.19AU/mL). Clinically, she wasasymptomatic. Again, she underwent extensive workup withbronchoscopy, and bronchoalveolar lavage was negative for
Figure 1: Gastric biopsy showing chronic gastritis with lymphoidaggregates and nonnecrotizing granulomatous inflammation withmultinucleated giant cells.
Figure 2: CT chest showing large necrotic mass.
2 Case Reports in Rheumatology
any infection or malignancy. She was diagnosed with GPArelapse and treated with rituximab 375mg/m2 every weekfor 4weeks and was started on azathioprine 50mg/day formaintenance therapy. Gradually, the azathioprine dose wasincreased to 150mg/day over next 2 months. She was fol-lowed up as outpatient closely with repeat CT chest every 6months, which showed regression of the lung lesion. Ap-proximately, 2 years since her initial presentation, she was incomplete remission with resolution of the lung lesion. In-terestingly, about a year later, routine follow-up labs in theclinic revealed hematuria with 6 RBCs per high-power field(normal 04 per high-power field) and urine protein cre-atine ratio of 0.67 equivalent to 24 hours urinary protein of670mg. Follow-up 24-hour urine collection showed pro-teinuria of