An Interesting Case of Nonlupus Full-House Nephropathy

Full-house immunofluorescence and endothelial tubuloreticular inclusions are known as characteristic features of lupus nephritis. However, both features are not pathognomonic for lupus nephritis. A kidney biopsy specimen showing full-house immunofluorescence pattern in the absence of autoantibodies and classical clinical features of Systemic Lupus Erythematosus (SLE) is now considered as nonlupus full-house nephropathy (FHN). Nonlupus FHN may be idiopathic or due to other disease processes known as secondary nonlupus FHN. Here, we report the case of a 36-year-old female who presented with nephrotic proteinuria with bland urine sediment. Additional analyses revealed normal serum antinuclear antibody (ANA), normal anti-double-stranded DNA (anti-dsDNA) antibodies, and normal serum C3 and C4 levels. A renal biopsy showed a normal-appearing glomerulus without any proliferation or capillary wall thickening and widespread glomerular immune deposits (full-house effect; IgA, IgG, IgM, C3, and C1Q) on direct immunofluorescence. Renal electron microscopy showed diffuse effacement of visceral epithelial cell foot processes and mesangial electron dense deposits. The patient was diagnosed as nonlupus FHN. There is a controversial role of steroids and other immunosuppressive drugs in the treatment of nonlupus FHN patients, but our case patient responded favourably to steroid therapy. The term nonlupus FHN can be used as an umbrella term for patients who do not satisfy the clinical and serological criteria of SLE.

Sickle Cell Disease with Dermatomyositis - a Rare and Complex Comorbidity

Introduction and Case Presentation - A 4 yrs old female with sickle cell disease (SCD) and intermittent asthma presented with polyarthralgia predominantly involving bilateral hip and knee joints and became non-ambulatory over a course of 2 months. She developed chronic facial swelling, and a pruritic erythematous rash involving face, extensor surface of the hand and the right knee with significant weight loss. Physical examination was significant for heliotropic rash on the eyelids, Also present were Gottron's papules and macules on both hands and right knee along with right leg tenderness, muscle weakness, wasting and decreased range of motion at bilateral hip joints along with inguinal lymphadenopathy. Investigations were significant for severe anemia with hyperactive bone marrow, metabolic acidosis, normonatremic dehydration with absence of any evidence of an ongoing infectious process. Her Anti Nucleic acid antibody (ANA) panel, Aldolase, Rheumatoid factor and Angiotensin-1-Converting Enzyme levels were unremarkable. Creatine kinase levels were near normal. Her Neopterin and LDH levels were significantly elevated. Imaging with MRI scan with multiplanar multisequence of bilateral lower extremities and Pelvis showed significant diffuse myositis and soft tissue swelling. The diagnostic criterion for Juvenile Dermatomyositis include: (1) the typical pathognomonic rashes, (2) elevated muscle enzymes, (3) symmetric proximal muscle weakness and neck flexors, (4) muscle biopsy characteristic of juvenile dermatomyositis, and (5) EMG findings characteristic of juvenile dermatomyositis. Having ruled out an infectious process a muscle biopsy was performed, which also was subjected to Electron Microscopic (EM) analysis as the patient did not have extremely high muscle enzymes, necessitating a muscle biopsy . Hematoxylin & eosin stained sections were compatible with inflammatory myopathy. Ultrastructural examination demonstrated myofiber size variability, frequent rounded atrophic fibers with myofibrillar disarray, internalized nuclei, and increased interstitial collagen deposition. Endomysial capillaries were decreased in number, but showed reactive endothelial changes. Some showed prominent endothelial tubuloreticular inclusions (Figure),characteristic of JD. In summary, absence of serologic and tissue evidence of any other inflammatory myopathy, offending pharmacotherapy, infectious disease and presence of imaging and tissue evidence (vascular injury and tubuloreticular inclusions) comprised the work up of a child with SCD with Dermatomyositis. Management- Prompt treatment with prednisone (2 mg/kg/day), methotrexate (10 mg) weekly and monthly IVIG (2gm/kg/dose) infusions was started, once diagnosis was confirmed showing a dramatic clinical response. Prednisone was slowly tapered after 1 month of treatment. She showed gradual improvement in her symptoms, the strength in proximal muscle in both upper and lower limbs improved eventually to a point where the contractures in the elbows and knees improved and she started ambulating without support. Patient's Hydroxyurea was restarted at a low dose of 15mg/kg/day and increased to 20 mg/kg/day slowly, as her systemic symptoms of Dermatomyositis subsided. Discussion- Working up a child with SCD who presents with sudden onset non weight bearing can be complicated. Vaso-occlusive bony pain crisis , Osteomyelitis , septic arthritis are common clinical scenarios, but an underlying rheumatologic illness in pediatric SCD patient mimicking a sickle cell pain crisis presents a unique diagnostic challenge one which, albeit has been reported in literature, but rarely includes electron microscopic ultrastructural examination as part of evidence and work up. This patient's relatively mild muscle enzyme elevation and Hydroxyurea therapy made the initial diagnosis more challenging. We present the first pediatric SCD patient with clinically and pathologically proven case of Dermatomyositis with EM evidence, highlighting a unique clinical scenario ,diagnostic challenges and management strategies. Figure 1 Figure 1. Disclosures Jain: Octapharma: Consultancy; CSL Behring: Consultancy, Speakers Bureau; GBT: Consultancy; Blue Bird Bio: Consultancy; Takeda: Consultancy, Speakers Bureau.

Sensitivity and Specificity of Pathologic Findings to Diagnose Lupus Nephritis

Background and objectivesIn 2012, the Systemic Lupus International Collaborating Clinics proposed that lupus nephritis, in the presence of positive ANA or anti-dsDNA antibody, is sufficient to diagnose SLE. However, this “stand-alone” kidney biopsy criterion is problematic because the ISN/RPS classification does not specifically define lupus nephritis. We investigated the combination of pathologic features with optimal sensitivity and specificity for the diagnosis of lupus nephritis.Design, setting, participants, & measurementsThree hundred consecutive biopsies with lupus nephritis and 560 contemporaneous biopsies with nonlupus glomerulopathies were compared. Lupus nephritis was diagnosed if there was a clinical diagnosis of SLE and kidney biopsy revealed findings compatible with lupus nephritis. The control group consisted of consecutives biopsies showing diverse glomerulopathies from patients without SLE, including IgA nephropathy, membranous glomerulopathy, pauci-immune glomerulonephritis, membranoproliferative glomerulonephritis (excluding C3 GN), and infection-related glomerulonephritis. Sensitivity and specificity of individual pathologic features and combinations of features were computed.ResultsFive characteristic features of lupus nephritis were identified: “full-house” staining by immunofluorescence, intense C1q staining, extraglomerular deposits, combined subendothelial and subepithelial deposits, and endothelial tubuloreticular inclusions, each with sensitivity ranging from 0.68 to 0.80 and specificity from 0.8 to 0.96. The presence of at least two, three, or four of the five criteria had a sensitivity of 0.92, 0.8, and 0.66 for the diagnosis of lupus nephritis, and a specificity of 0.89, 0.95, and 0.98.ConclusionsIn conclusion, combinations of pathologic features can distinguish lupus nephritis from nonlupus glomerulopathies with high specificity and varying sensitivity. Even with stringent criteria, however, rare examples of nonlupus glomerulopathies may exhibit characteristic features of lupus nephritis.

Tubuloreticular Inclusions in the Absence of Systemic Lupus Erythematosus and HIV Infection: A Report of Three Pediatric Cases

Tubuloreticular inclusions (TRIs) are subcellular structures located within the cisternae of endoplasmic reticulum. Formation of TRIs has been linked to the exposure of excess interferon (IFN), either from endogenous or exogenous sources. In renal disease, TRIs have been most commonly associated with systemic lupus erythematosus (SLE), and human immunodeficiency virus-associated nephropathy (HIVAN). Case reports of patients with renal biopsies showing TRIs without underlying SLE or HIV are infrequent in adults, and to our knowledge none have been reported in children. We report 3 pediatric cases in which the renal biopsy showed TRIs on electron microscopy without underlying SLE or HIV infection. The first patient presented at 2 years of age with nephrotic syndrome and renal failure. His renal biopsy revealed focal segmental glomerulosclerosis and TRIs. The second patient presented at 6 months of age with infantile nephrotic syndrome, and his renal biopsy revealed membranous glomerulopathy and TRIs. The last patient presented at 4 years of age with acute kidney injury of unclear etiology leading to chronic kidney disease. Her biopsy revealed acute and chronic tubulointerstitial nephritis with TRIs. Despite extensive evaluation in all 3 patients, including testing for HIV infection and SLE, we could not identify an underlying etiology to explain the presence of TRIs. In conclusion, renal biopsy with TRIs in the absence of underling SLE and HIV remains obscure. We propose a possible role for excess IFN triggered by an abnormal immune response to common viral infections in the formation of TRIs and renal injury.