Exostosin-1/exostosin-2 expression and favorable kidney outcomes in lupus nephritis: a retrospective cohort study.

INTRODUCTION/OBJECTIVES: The heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes. METHODS: The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure. RESULTS: Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure. CONCLUSION: EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points • Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus. • Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function. • The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications.

SARS-CoV-2-Related Subacute Thyroiditis, Myocarditis, and Hepatitis After Full Resolution of COVID-19 Serum Markers.

BACKGROUND Subacute thyroiditis, myocarditis, and hepatitis are inflammatory disorders that may develop after viral infections, including SARS-CoV-2. These entities may appear after resolution of the respiratory syndrome. CASE REPORT A previously healthy 64-year-old male patient came to the hospital reporting severe chest pain. He had a history of a COVID-19 pneumonia with PCR confirmation 4 weeks before. On admission to the Coronary Care Unit (CCU), the patient had a negative PCR for SARS-CoV-2; the following tests were performed: total T3 643.4 ng/dl (reference 35-193 ng/dl), total thyroxine 12.0 µg/dl (reference 4.8-11.7 µg/dl), free T4 1.85 ng/dl (reference 0.7-1.48 ng/dl), TSH 0.01 µIU/ml (reference 0.35-4.94 µIU/ml); total bilirubin 0.76 mg/dl (reference 0.0-1.5 mg/dl), alkaline phosphatase 185 U/L (reference 40-150 U/L), alanine aminotransferase 194.6 U/L (reference 6-66 U/L), aspartate aminotransferase 93.4 U/L (reference 9-55 U/L); on admission to the CCU high-sensitivity troponin I 548.3 pg/ml (reference 0.0-34.2 pg/ml), after 24 h in the CCU 801 pg/ml, and after 11 days (as an outpatient) 4.5 pg/ml. A thyroid gammagram revealed absent uptake of the radionuclide. Normal cardiac gammagraphy and cardiac enzymes ruled out myocardial ischemia and infarction. The following diagnoses were made: myocarditis, subacute thyroiditis, and reactive hepatitis due to SARS-CoV-2 infection. CONCLUSIONS COVID-19 has been demonstrated to be a multisystemic inflammatory disorder. The serious illness that developed in our patient after relief of his pulmonary disease underlines this nature. We suggest close follow-up of patients even after apparent clinical resolution, and performing thyroid, myocardial, and liver tests if clinically indicated.

IgG4-Related Fibrous Thyroiditis (Riedel's Thyroiditis): A Case Report.

BACKGROUND Riedel's thyroiditis is a rare form of immunoglobulin G (IgG) 4-related invasive fibrosis of the thyroid gland; given its scarce incidence, standardized therapeutic guidelines are unavailable. Although complications are unusual, obstructive symptoms produced by the stony-hard goiter may put patients' lives at risk. The diagnosis must be biopsy-proven, and treatment consists of thyroid hormone replacement and anti-inflammatory drugs, although sometimes thyroidectomy may be required. CASE REPORT A 69-year-old woman presented with a 7-month history of progressive hypothyroidism and obstructive dysphagia. On physical examination, she had a large, stony-hard goiter. A Doppler ultrasound study revealed a massive, avascular enlargement of the thyroid gland. A computed tomography scan failed to demonstrate any extrathyroidal extension of the abnormal tissue. A Tru-Cut biopsy of the thyroid was performed. Extensive replacement of thyroid follicles by prominent bands of fibrous tissue was observed, with follicular obliteration and mild focal occlusive phlebitis. A lymphoplasmacytic infiltrate was clearly identified; no oxyphilic nor giant cells were found. On immunohistochemistry, the immunoglobulin G (IgG) 4/IgG ratio in the plasma cell infiltrate was 40%; increased serum IgG4 levels were also found, supporting the diagnosis of Riedel's thyroiditis. The patient was successfully treated with levothyroxine replacement and tamoxifen with prompt resolution of obstructive symptoms. CONCLUSIONS Fibrous thyroiditis should be considered in the differential diagnosis of primary hypothyroidism in a patient with a stony-hard goiter. Although steroids are often used as a therapeutic strategy for this disease, our patient had an excellent therapeutic response to tamoxifen, avoiding adverse effects associated with steroid therapy, the higher cost of monoclonal antibody therapy, and surgery-associated risks.