Early azathioprine in acute Vogt-Koyanagi-Harada disease: a prospective 24-month follow-up study with multimodal imaging and electroretinogram

Background: First-line immunosuppressive therapy (IMT) associated with high-dose corticosteroid (CS) has been proposed for the treatment of acute Vogt-Koyanagi-Harada disease (VKHD) to prevent chronicity and to prevent long-term CS side effects. However, there are very few studies that systematically evaluated visual and inflammatory outcomes in acute VKHD with early IMT. This study aimed to evaluate the outcome of high-dose corticosteroids with early addition of azathioprine (AZA) in patients with acute Vogt-Koyanagi-Harada disease (VKHD) followed for 24-month with systematic multimodal and electroretinogram exams.Methods: Prospective interventional study. Fifteen consecutive patients (30 eyes) with acute VKHD at a tertiary uveitis referral centre were followed for 24 months with systematic multimodal and full-field electroretinogram (ffERG) exams. Patients were treated with intravenous methylprednisolone followed by oral prednisone 1mg/kg/daily (CS) with slow taper and AZA introduction within 4 months. Anterior uveitis relapse, subclinical inflammation, best-corrected visual acuity (BCVA) and ffERG parameters were analyzed.Results: Fifteen patients (14 female) with a median age of 32 years were included. In the first month, 27 eyes (90%) had BCVA ≥20/40; at M24, all eyes (100%) had BCVA ≥20/25. Uveitis resolved in 28 eyes (93.3%) and became chronic recurrent in 2 eyes (6.7%); subclinical inflammation was still present in all eyes during the 24-month follow-up. ffERG parameters initially improved in all eyes; at M24, 23 eyes (76.7%) had subnormal results and 20 eyes (66.7%) had stable parameters. Eyes with very early treatment (n=12) had lower indocyanine green angiography score than eyes with early treatment (n=18) at M1 (p=0.012), but they had similar rates of recurrence, complications and ffERG parameters. Conclusion: Early AZA associated with high-dose corticosteroid was effective in improving BCVA and in controlling clinical inflammation. Isolate subclinical inflammation persisted in all eyes with no impact on ffERG in, at least, two thirds of these eyes, indicating that isolate subclinical inflammation may not be enough to indicate treatment increment.

Subacute thyroiditis during early pregnancy: a case report and literature review

Background Subacute thyroiditis (SAT) is rarely diagnosed in pregnant women, and only 7 cases have been reported to date. Thyroid dysfunction, especially hyperthyroidism, during pregnancy has been associated with both maternal and neonatal complications. Thus, the early diagnosis and treatment of SAT during pregnancy may be beneficial. We present a case report and literature review to complement the diagnostic evaluation and management of SAT during pregnancy. Case presentation A 27-year-old woman presented in gestational week 17 of her first pregnancy and had a negative prior medical history. She presented to the Endocrinology Department complaining of neck pain for one month that had intensified in the last five days. Physical examination revealed a diffusely enlarged thyroid gland that was firm and tender on palpation. The patient also had an elevated temperature and heart rate. The increasing and long-lasting pain coupled with a decreased level of thyroid-stimulating hormone indicated hyperthyroidism. Ultrasound findings were indicative of SAT. Importantly, the pain was so severe that 10 mg of oral prednisone per day was administered in gestational week 18, which was increased to 15 mg/d after 10 days that was discontinued in week 28. Levothyroxine was started in gestational week 24 and administered throughout the pregnancy. The patient responded well to the treatments, and her neck pain disappeared in gestational week 21. She gave birth to a healthy male in gestational week 41. Conclusion SAT can be diagnosed and effectively managed during pregnancy, thus benefiting mothers and infants.

Extensive Longitudinal Transverse Myelitis after Influenza A Virus Infection in a Patient with Systemic Lupus Erythematosus

Transverse myelitis (TM) is a rare complication seen in 1–2% of patients with systemic lupus erythematosus (SLE). Viral infections may cause TM in these patients by causing a dysregulation of their immune system. We report a 30-year-old woman with SLE who had influenza A and a few days later developed urinary retention, bilateral lower extremity paralysis, upper extremity weakness, and optic nerve and macular edema. Magnetic resonance imaging showed C4-T12 hyperintense lesions consistent with TM. She was treated with intravenous methylprednisolone 1 g daily for 3 days and then 6 cycles of monthly intravenous cyclophosphamide. This treatment was followed by oral prednisone. She had a remarkable clinical response. Visual acuity improved to her baseline, and muscle strength almost fully recovered. Clinicians should be aware that viral infections, including influenza, may induce TM. This case highlights the importance of early recognition and prompt treatment with immunosuppressive drugs in such cases.

Effect of pulsed intravenous methylprednisolone with alternative low-dose prednisone on high-risk IgA nephropathy: a 18-month prospective clinical trial

Full-dose prednisone (FP) regimen in the treatment of high-risk immunoglobulin A nephropathy (IgAN) patients, is still controversial. The pulsed intravenous methylprednisolone combined with alternative low-dose prednisone (MCALP) might have a more favorable safety profile, which has not been fully investigated. Eighty-seven biopsy-proven IgAN adult patients and proteinuria between 1 and 3.5 g/24 h after ACEI/ARB for at least 90 days were randomly assigned to 6-month therapy: (1) MCALP group: 0.5 g of methylprednisolone intravenously for three consecutive days at the beginning of the course and 3rd month respectively, oral prednisone at a dose of 15 mg every other day for 6 months. (2) FP group: 0.8–1.0 mg/kg/days of prednisone (maximum 70 mg/day) for 2 months, then tapered by 5 mg every 10 days for the next 4 months. All patients were followed up for another 12 months. The primary outcome was complete remission (CR) of proteinuria at 12 months. The percentage of CR at 12th and 18th month were similar in the MCALP and FP groups (51% vs 58%, P = 0.490, at 12th month; 60% vs 56%, P = 0.714, at 18th month). The cumulative dosages of glucocorticoid were less in the MCALP group than FP group (4.31 ± 0.26 g vs 7.34 ± 1.21 g, P < 0.001). The analysis of the correlation between kidney biopsy Oxford MEST-C scores with clinical outcomes indicated the percentages of total remission was similar between two groups with or without M1, E1, S1, T1/T2, and C1/C2. More patients in the FP group presented infections (8% in MCALP vs 21% in FP), weight gain (4% in MCALP vs 19% in FP) and Cushing syndrome (3% in MCALP vs 18% in FP). These data indicated that MCALP maybe one of the choices for IgAN patients with a high risk for progression into ESKD.Trial registration: The study approved by the Chinese Clinical Trial Registry (registration date 13/01/2018, approval number ChiCTR1800014442, https://www.chictr.org.cn/).

Successful Outpatient Management of Severe Ionized Hypercalcemia Secondary to Cholecalciferol Ingestion in a Puppy

ABSTRACT A 4 mo old female intact boxer was presented because of polyuria, lethargy, and vomiting after ingestion of cholecalciferol rodenticide roughly 3 days prior. Blood work revealed an ionized hypercalcemia 2.23 mmol/L (reference range 1.04–1.33 mmol/L) on presentation. Because of financial limitations, the patient was unable to be hospitalized for standard of care. She was treated with a pamidronate infusion and discharged with medical management to include oral prednisone, furosemide, and subcutaneous fluids. The dog’s signs, body weight, and biochemical parameters were serially monitored over 3 wk as the ionized hypercalcemia resolved. To the authors’ knowledge, this is the first published report documenting a successful outpatient medical protocol for potentially life-threatening hypercalcemia secondary to cholecalciferol toxicosis in a puppy.

A Randomized, Controlled Trial of Prednisone Plus Cyclophosphamide in Patients with Advanced-stage IgA Nephropathy

BackgroundTreatments with glucocorticoids or immunosuppressants in IgA nephropathy remain controversial, especially in IgA nephropathy patients with renal insufficiency and small quantities of proteinuria. So far, no randomized controlled study has investigated whether cyclophosphamide has a protective effect on IgA nephropathy independent of glucocorticoids.MethodsWe conducted a single-center, randomized, controlled trial ((NCT01758120)). 135 IgA nephropathy patients with elevated plasma creatinine concentrations (1.3-3.0 mg/dl in males and 1.0-3.0 mg/dl in females), regardless of proteinuria level, were enrolled in and randomized 1:1 to the prednisone alone group or prednisone plus cyclophosphamide group. The daily dosage of oral prednisone was initiated at 0.5 mg/kg/d taken every morning for 2 months and then tapered by 20% each month for the next 4 months in prednisone alone group. In prednisone plus cyclophosphamide group cyclophosphamide was given in monthly pulses of 1.0 g for 6 months, while the prednisone dosage was the same as prednisone group. The two primary end points were a combination of reaching end-stage renal disease (ESRD) or doubling of serum creatinine or death and absolute changes in eGFR (estimated glomerular filtration rate) at 36 months.ResultsOverall, 135 patients were enrolled in our study. There was no significant difference between the two groups at baseline. The two groups had similar primary composite renal outcomes, which occurred in 4 participants (5.97%) in the prednisone alone group and 5 (7.35%) in the prednisone plus cyclophosphamide group (hazard ratio, 1.13 [95% CI, 0.30 to 4.19]; P = 0.861). Additionally, no significant difference in eGFR absolute change in three years was found between the two groups (0.09 (-7.42, 12.00) ml/min/1.73 m2 in the prednisone alone group vs. 3.24 (5.025, 9.59) ml/min/1.73 m2 in the prednisone plus cyclophosphamide group; P = 0.578). Proteinuria was reduced similarly in both groups. Treatment with cyclophosphamide led to more adverse events.ConclusionsOur study showed that corticosteroids plus cyclophosphamide did not increase the renal benefit of patients with advanced-stage IgA nephropathy but increased adverse effects compared with corticosteroids alone. Trial registration: ClinicalTrials.gov, NCT01758120. Registered 1 July 2012, https://clinicaltrials.gov/ct2/show/NCT01758120

Encephalopathy With Alternating Hemispheric MRI Abnormalities

A 21-year-old woman with a long-standing history of migraine sought care at her local provider for a 1-week history of confusion and mixing up her words. She then had a witnessed seizure, with dyscognitive features and secondary generalization. On hospitalization, electroencephalography demonstrated left temporal theta slowing and sharp waves. Magnetic resonance imaging showed patchy T2-signal abnormality, nonenhancing, in the left temporal region (only a report was available). Thyroid peroxidase antibodies were increased at 271 IU/mL. A diagnosis of an autoimmune encephalopathy was made, and the patient was treated with phenytoin, levetiracetam, and high-dose corticosteroids, followed by a slow oral prednisone taper. The patient improved cognitively but had considerable emotional lability and an increase in headache frequency and severity and, thus, sought a second opinion. Blood was drawn for genetic testing. The patient died in her sleep a short time later, most likely in the context of sudden unexplained death in epilepsy. Her genetic testing results became available 1 month later, which showed findings consistent with MELAS syndrome: heteroplasmic sequence variation m.3243A>G (tRNA Leu) and homoplasmic rare variant m.2294A>G (16S rRNA). Encephalopathy or encephalitis of subacute onset with fluctuating course is not unique to autoimmune encephalitis. Common acquired metabolic disorders must be considered and excluded in all cases, such as deficiencies of vitamin B12 and folate, hypothyroidism, sepsis, and central nervous system–active medications.

Goose Bumps and Memory Loss

A 46-year-old man had an episode of loss of awareness while driving home. He was found in a cul de sac by his neighbor and was acting confused. He was brought to the emergency department; while there, he started having recurrent episodes of goose bumps (goose flesh) involving half of his body associated with a “wavelike” sensation that would typically begin in the lower extremities and spread upward. He also had some speech difficulty. Physical and neurologic examinations were unremarkable, except for mild cognitive deficits. Video electroencephalographic monitoring showed frequent independent left and right temporal ictal and interictal discharges. Magnetic resonance imaging of the brain showed fluid-attenuated inversion recovery hyperintensity in the bilateral hippocampi. Cerebrospinal fluid analysis showed a mildly increased total protein concentration but no supernumerary oligoclonal bands and normal nucleated cell count and immunoglobulin G index. Serum autoimmune epilepsy evaluation was remarkable for leucine-rich, glioma-inactivated protein 1-immunoglobulin G seropositivity. The patient was diagnosed with leucine-rich, glioma-inactivated protein 1- immunoglobulin G antibody–associated autoimmune seizures presenting with pilomotor seizures. Before autoimmune work-up, the patient had been treated with a gradual escalation of antiseizure medications. The seizures continued. He was subsequently started on intravenous methylprednisolone. He was seizure free and was transitioned to an oral prednisone taper. He was subsequently started on a 6-week regimen of intravenous immunoglobulin. He was also started on mycophenolate mofetil. On follow-up clinic visits, the patient had no recurrence of seizures and disclosed no cognitive dysfunction except for mild inattention. Three years after the patient’s initial episode, the antiseizure medications and mycophenolate mofetil were gradually tapered, without recurrence. Leucine-rich, glioma-inactivated protein 1-immunoglobulin G–associated autoimmunity is typically seen among older patients (>50 years), more commonly men. Symptoms commonly include seizures and cognitive dysfunction, presenting as memory loss and disorientation.

A Woman With Subacute Numbness of the Trunk, Arms, and Legs

A 39-year-old woman had development of new-onset numbness in her left arm. This progressed over 2 to 3 weeks to involve the left axilla, trunk, lower extremities, and genital region. She had mild imbalance and left-sided weakness but remained ambulating without a gait aid. Repeated magnetic resonance imaging of the cervical spine showed the longitudinally extensive T2 lesion in a central location on axial sequences, with linear, dorsal, subpial gadolinium enhancement extending more than 2 vertebral segments. The magnetic resonance image findings were most suggestive of spinal cord neurosarcoidosis. Computed tomography of the chest showed bilateral hilar adenopathy. Serum levels of angiotensin-converting enzyme were normal. Transbronchial lung biopsy showed noncaseating granulomas. Noncaseating granulomas were confirmatory of pulmonary sarcoidosis, which led to a diagnosis of spinal cord neurosarcoidosis. Treatment with intravenous methylprednisolone for 5 days was repeated, followed by oral prednisone for 2 months. Her neurologic symptoms improved, and repeated magnetic resonance image showed a marked decrease in T2 hyperintensity and gadolinium enhancement consistent with interval response to treatment. A slow prednisone taper over 9 months was initiated. Spinal cord neurosarcoidosis often presents with an isolated myelopathy without symptoms of pulmonary sarcoidosis (eg, cough, dyspnea). The presentation can range from a subacute onset mimicking transverse myelitis (as in this case patient) to a more insidious progressive myelopathy over months to years.

Personality Changes, Cognitive Decline, and Jerking Movements

A 64-year-old man had development of abnormal movements characterized by grimacing of the left hemiface and posturing of the ipsilateral arm. He had a generalized tonic-clonic seizure, followed by cognitive decline requiring assistance for most activities of daily living. He was readmitted to the hospital for neurologic evaluation. His heart rate was 120 beats/min, he was afebrile. On neurologic examination, he had a Mini-Mental State Examination (MMSE) score of 16/30. The patient was oriented to person only, and he had multiple, frequent, left hemibody jerks during examination. Cerebrospinal fluid analysis indicated increased protein concentration but otherwise normal findings. Laboratory abnormalities included a serum sodium and antibodies to leucine-rich, glioma-inactivated protein 1. Electroencephalography revealed diffuse slowing and bilateral temporal lobe epileptiform discharges. Magnetic resonance imaging of the brain showed T2/fluid-attenuated inversion recovery hyperintensities in the bilateral hippocampi and amygdalae and gadolinium enhancement in the same regions. Brain 18F-fludeoxyglucose–positron emission tomography demonstrated hypermetabolism in the mesiotemporal lobes bilaterally. A diagnosis of limbic encephalitis associated with leucine-rich, glioma-inactivated protein 1-immunoglobulin G antibodies was. The unilateral facial and arm movements were consistent with faciobrachial dystonic seizures and are pathognomonic of the disorder. The patient’s seizure frequency did not improve with antiepileptic drug therapy. The patient was treated with intravenous methylprednisolone, followed by plasmapheresis. This resulted in substantial improvement of his cognitive dysfunction and decrease in the faciobrachial dystonic seizures frequency. Therapy was transitioned to oral prednisone and the patient was discharged from the hospital. This patient had classic features of leucine-rich, glioma-inactivated protein 1 antibody encephalitis: faciobrachial dystonic seizures, personality changes, subacute cognitive decline, hyponatremia, and improvement with immunotherapy.