Improvement of renal and non-renal SLE outcome measures on sirolimus therapy - A 21-year follow-up study of 73 patients.

The safety, tolerance, and selected renal and non-renal outcome measures were evaluated in 73 SLE patients who received sirolimus therapy for more than 3 months in our institution over the past 21 years. In 12 patients who had lupus nephritis, proteinuria (p = 0.0287), hematuria (p = 0.0232), anti-DNA antibody levels (p = 0.0028) and steroid use were reduced (p = 0.0200). In the non-renal cohort of 61 patients, anti-DNA antibody levels (p = 0.0332) and steroid use were reduced (p = 0.0163). Both in the renal and non-renal cohorts, C3 (renal p = 0.0070; non-renal p = 0.0021) and C4 complement levels were increased (renal p = 0.0063; non-renal p = 0.0042) Adverse effects of mouth sores (2/73), headaches (1/73), and gastrointestinal discomfort were noted in a minority of patients (6/73). Sirolimus was only discontinued in two of 73 patients due to headache and recurrent infections, respectively. This study suggests that sirolimus is well tolerated and exerts long-term therapeutic efficacy in controlling renal and non-renal manifestations of SLE.

A rare case of Sweet syndrome secondary to melioidosis.

BACKGROUND: Melioidosis is an emerging infection in South Asia caused by Burkholderia pseudomallei with various clinical presentations that include pneumonia, bacteraemia, arthritis, and deep-seated abscesses. Various cutaneous manifestations have been described in association with melioidosis. However Sweet Syndrome secondary to melioidosis has not been reported in the literature. Herein we describe the first case of Sweet syndrome secondary to melioidosis. CASE PRESENTATION: A 53-year-old previously healthy Sri Lankan female presented with high-grade fever, painful oral ulcers, odynophagia and multiple bilateral cervical lymphadenopathies for 1 month. She also had a loss of appetite and weight. She had oral ulcers and bilateral blepharitis. Dermatological examination revealed multiple tender papules with a mamillated appearance and targetoid lesions with a yellowish centre over the face, upper trunk and upper limbs. She also had multiple tender subcutaneous nodules over the extensor aspect of upper limbs. Her inflammatory markers were significantly elevated. Aspirate from a submental lymph node abscess revealed the growth of Burkholderia pseudomallei. Melioidosis antibody titer was > 10,240. The histology of the skin lesions of the face and left forearm showed a prominent neutrophilic infiltrate in the dermis and the morphological features were in favour of Sweet syndrome with panniculitis. She was started on intravenous meropenem 2 g daily and showed rapid clinical improvement with the disappearance of skin lesions as well as a reduction in inflammatory markers. CONCLUSION: Sweet syndrome is an uncommon inflammatory disorder known to be associated with upper respiratory tract and gastrointestinal infections, malignancies and the use of certain drugs. Melioidosis is an emerging infection with various cutaneous manifestations. This is the first case of melioidosis causing the secondary sweet syndrome. It emphasizes the importance of considering melioidosis as a potential aetiology in patients with Sweet syndrome.

Chorea as an initial and solitary manifestation of systemic lupus erythematosus with antiphospholipid syndrome in an elderly man.

Chorea can be an initial manifestation of systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). It has been mostly described in younger female adults in association with other manifestations of SLE. When chorea appears as an initial and only manifestation in SLE/APS patients, the establishment of the correct diagnosis is difficult, and it may be initially attributed to a more common aetiology. Here we report an elderly man who presented with a new onset of right-sided chorea without other clinical manifestations of SLE/APS. He started on steroids a year later, however, there was no improvement. His chorea was symptomatically managed along with aspirin, and hydroxychloroquine as he refused to be on additional immunosuppression. Anticoagulation was relatively contraindicated, and also not favoured by this patient; therefore, aspirin was initiated. Even in elderly patients, once the common etiologies of chorea have been worked up, we suggest doing a rheumatological evaluation. Early diagnosis and prompt treatment can prevent persistent neurological abnormality.

Embolic myocardial infarction with cardiac arrest as an initial manifestation of non-bacterial thrombotic endocarditis.

Non-bacterial thrombotic endocarditis, characterised by sterile vegetations, is commonly caused by systemic lupus erythematosus and is known to be complicated with embolic cerebrovascular disease. Embolic myocardial infarction with non-bacterial thrombotic endocarditis is extremely rare. We report a case of ventricular fibrillation arrest from presumed coronary embolisation in non-bacterial thrombotic endocarditis. While there are no standardised guidelines on the management of embolic myocardial infarction in endocarditis, it requires a multidisciplinary approach unique for every encountered clinical scenario.

Strongyloides stercoralis Hyperinfection Syndrome: A Neglected Cause of Abdominal Pain.

Strongyloides stercoralis infection is usually acquired from tropics or subtropics, often causes asymptomatic chronic infection, but in immunosuppressed, it can lead to hyperinfection syndrome. We report a case of chronic abdominal pain resulting from Strongyloides infection in a 55-year-old male with a history of partial small bowel resection for small intestinal lymphoma and a recent diagnosis of chronic kidney disease with proteinuria on steroid therapy. He presented with chronic abdominal pain, nausea, loss of appetite, and weight loss. Initial laboratory workup and imaging including retroperitoneal ultrasound and CT of the abdomen/pelvis were within normal limits, and he was discharged on acid suppression therapy. He was readmitted with worsening symptoms and underwent esophagogastroduodenoscopy (EGD) and duodenal biopsy, which revealed Strongyloides infection. We later discovered a travel history to Cambodia. His symptoms resolved with ivermectin therapy. This case highlights the importance of travel history, which can prevent unnecessary investigations and delay in the diagnosis.

Hypocalcemia with Immune Checkpoint Inhibitors: The Disparity among Various Reports.

Immune-related adverse events affecting parathyroid function are rarely reported with immune checkpoint inhibitors (ICPIs). Activating calcium-sensing receptor antibodies causing autoimmune hypoparathyroidism with nivolumab was recently reported. KEYNOTE-189 and CHECKMATE-067 trials reported a 21-29% hypocalcemia event rate, but the etiology of hypocalcemia was not reported. A chart review was performed to study patients receiving ICPI from 2015 to 2018 at multiple sites affiliated with Saint Vincent Hospital. The study population was divided into two groups based on the presence or absence of calcium altering conditions or medications. True hypocalcemia incidence was calculated after correcting calcium for albumin from the initiation of ICPI to their last follow-up. Group 1 (n = 83) includes patients with no calcium altering conditions or medications. Group 2 (n = 98) includes patients on calcium supplements (n = 17), vitamin D (n = 44), bisphosphonates (n = 24), >stage IIIB chronic kidney disease (CKD) (n = 5), and bone metastasis (n = 38). Hypocalcemia events in Group 1 vs. Group 2 were 8.4% and 19.3%, respectively. Our entire study demonstrated 26.8% vs. 1.1% of Grade I vs. II hypocalcemia events. However, after correcting the calcium for albumin, hypocalcemia incidence was 0.56% (n = 1). No further workup was done to investigate the etiology as that patient passed away. Our data suggest that the true hypocalcemia incidence after using albumin-corrected calcium values is very low in patients receiving IPCI, even in the presence of calcium altering factors. The percentage of patients with hypocalcemia is much higher and similar to the KEYNOTE-189 and CHECKMATE-067 trials when serum calcium values without albumin correction are used. Thus, the higher reported incidence of hypocalcemia in these trials is likely due to the reporting of serum calcium without albumin correction.

Clinical Characteristics of Early-Onset Gout in Outpatient Setting.

OBJECTIVE: The objective of this study is to investigate the clinical characteristics and treatment of patients with early-onset gout. METHODS: We retrospectively reviewed 327 adult patients with a first diagnosis of gout from 2008 to 2016 using the database of a multispecialty group practice in New England. Patients were classified into the following groups: age 30 years or younger at first diagnosis (group 1), age 31-40 years (group 2), and age over 40 years (group 3). The clinical characteristics and treatment of gout were compared among the three groups. RESULTS: We identified 87 patients in group 1 and 140 patients in group 2. Group 3 included 100 patients randomly chosen from the 7216 patients with a first diagnosis at age over 40 years. Patients within group 1 had significantly higher serum uric acid (sUA) levels at the time of diagnosis and a more prominent family history of gout. Younger patients (groups 1 and 2) had a significantly higher body mass index than patients over 40 years of age (group 3). A substantial number of younger patients also had hypertension or hyperlipidemia. The majority of younger patients met the 2012 American College of Rheumatology (ACR) guidelines for initiating urate-lowering therapy (ULT) on the basis of frequency of gout attacks, whereas the majority of patients over 40 years of age met the guidelines for ULT on the basis of chronic kidney disease. Patients over 40 years of age were more likely to achieve an sUA level less than 6.0 mg/dl. CONCLUSION: Patients with a first diagnosis of gout at age 40 years or younger frequently had cardiovascular risk factors and were less likely to achieve an sUA level less than 6.0 mg/dl compared with patients over 40 years of age who were treated in routine clinical practice. Clinicians should be aware that patients with early-onset gout may be an undertreated population with poor adherence to ULT and increased risk of recurrent gout and cardiovascular diseases.

A rare presentation of spontaneous atheroembolic renal disease: A case report.

BACKGROUND: Atheroembolic renal disease (AERD) is caused by occlusion of the small renal arteries from embolized cholesterol crystals arising from ulcerated atherosclerotic plaques. This usually manifests as isolated renal disease or involvement from systemic atheroembolic disease. Here we report a case of AERD that responded well to steroid therapy. CASE SUMMARY: A 62-year-old woman with a history of hypertension and stage IIIa chronic kidney disease was referred for rapidly worsening renal function over a 4-mo period. She complained of swollen legs, dyspnea on exertion, and two episodes of epistaxis about a month prior to admission. She reported no history of invasive vascular procedures, use of radio contrast agents, or treatment with anticoagulants or thrombolytic agents. Urinalysis showed a few red blood cells and granular casts. Serology was positive for cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). Non-contrast-enhanced computed tomography of the chest, abdomen, and pelvis showed diffuse atherosclerotic changes in the aortic arch. Thus, c-ANCA-associated vasculitis was suspected, and the patient was started on pulse intravenous methylprednisolone. Her renal biopsy showed evidence of AERD. She was discharged with oral prednisone, and her renal function continued to improve during the initial follow-up. CONCLUSION: In cases of non-vasculitis-associated ANCA, a high degree of clinical suspicion is required to pursue the diagnosis of spontaneous AERD in patients with clinical or radiological evidence of atherosclerotic burden. Although no specific treatment is available, the potential role of statins and steroids requires exploration.

Forme Fruste in Recurring Mid-Ventricular Variant of Takotsubo Cardiomyopathy.

BACKGROUND Takotsubo cardiomyopathy (TC) is characterized as acute left ventricular dysfunction precipitated by intense emotional or physiological stress. The mid-ventricular variant of TC usually has akinesis, with or without ballooning of the mid-ventricular segment, and a hyperdynamic base and apex. Recurrence of the typical and atypical (reversed and mid-ventricular type) forms has been reported in only a very small number of cases. We report a forme fruste presentation of mid-ventricular variant of TC. CASE REPORT A 69-year-old woman with a prior history of stress-induced cardiomyopathy presented with complaint of moderate intensity, persistent, sub-sternal chest discomfort. She reported that her symptoms were similar to those she had during a previous hospitalization in 2015, and this time cited the death of her mother as an inciting stressor. No significant obstructive flow-limiting coronary artery disease was found on cardiac catheterization. However, the left ventriculogram was suggestive of mid-ventricular pattern of TC. Her first symptomatic episode of apparent TC did not reveal completion of the mid-ventricular pattern of the TC variant. The subsequent episode, during this hospitalization, manifested as a completed version of her initial apparent forme fruste of mid-ventricular variant of TC. CONCLUSIONS TC may present in a myriad of clinical forms that must be considered in the evaluation of patients with suspected acute coronary syndromes or cardiomyopathy. Treatment is mainly supportive, and recurrence rates range from 7.7% to 11.4%. To the best of our knowledge, this forme fruste presentation has not been previously reported in recurrent variants of TC.

Splenic infarction secondary to myelodysplastic syndrome: unravelling more etiologies.

Myelodysplastic syndrome (MDS) is a neoplastic disorder resulting in dysplasia and apoptosis of the hematopoietic clonal cells. The presenting features of MDS are usually dependent on the cellular lineage affected in the bone marrow (BM). Generally, MDS presents in older adults with recurrent infections, anemia, and bleeding tendencies. However, until now, there are no cases of splenic infarction in MDS. Splenic infarction is a rare event and is often reported in myeloproliferative or thromboembolic disorders. In this case report, we present splenic infarction; a never reported clinical manifestation in an MDS patient.

Immune Checkpoint Inhibitor-Induced Hypoparathyroidism Associated With Calcium-Sensing Receptor-Activating Autoantibodies.

Context: Whereas therapy with immune checkpoint inhibitors (ICIs), such as nivolumab, have substantially improved survival in several types of cancer, increased attention has been given to adverse immune events associated with their use, including the development of endocrine autoimmunity. Objectives: First, to describe a patient with a 2-year history of metastatic small cell lung cancer who had been treated with nivolumab a few months before presentation with the signs and symptoms of severe hypocalcemia and hypoparathyroidism. Second, to investigate the etiology of the patient's hypoparathyroidism, including the presence of activating autoantibodies against the calcium-sensing receptor (CaSR), as humoral and cellular immune responses against the CaSR have been reported in patients with autoimmune hypoparathyroidism. Participants: A 61-year-old female was admitted with persistent nausea, vomiting, epigastric pain, constipation, and generalized weakness. Laboratory analyses showed low total serum calcium, ionized calcium, and parathyroid hormone (PTH). The patient was diagnosed with severe hypocalcemia as a result of autoimmune hypoparathyroidism after testing positive for CaSR-activating autoantibodies. Interventions: She was treated with intravenous calcium gluconate infusions, followed by a transition to oral calcium carbonate, plus calcitriol, which normalized her serum calcium. Results: Her serum PTH remained low during her hospitalization and initial outpatient follow-up, despite adequate repletion of magnesium. Conclusions: This case illustrates autoimmune hypoparathyroidism induced by ICI blockade. As ICIs are now used to treat many cancers, clinicians should be aware of the potential risk for hypocalcemia that may be associated with their use.

A Rare Cause of Ascites-Disseminated TB with Peritonitis in a Middle-Aged Female.

BACKGROUND: Disseminated tuberculosis (TB) has been increasingly recognized in adults in the recent times due to increased prevalence of immune suppression. Here we describe a case of 47-year-old female who presented with disproportionate ascites where the diagnosis of disseminated TB was delayed. CASE REPORT: A 47-year-old previously healthy female presented with generalised body swelling with disproportionate ascites and loss of appetite and weight for four-month duration. She denied any contact or past history of TB and reported no respiratory symptoms. Physical examination revealed significant ascites. There was no lymphadenopathy or hepatosplenomegaly. Respiratory system examination was normal. Her Erythrocyte Sedimentation Rate (ESR) was above 100. Tuberculin skin test was positive with 17mm. Contrast Enhanced Computed Tomography (CECT) abdomen revealed chronic liver disease with ascites. Diagnostic laparoscopy was in favour of miliary TB and the peritoneal biopsy revealed granulomatous inflammation with caseous necrosis, suggestive of TB. The patient was started on antituberculosis treatment and subsequently improved. CONCLUSION: TB peritonitis due to disseminated TB should be considered in the differential diagnosis of disproportionate ascites. Even though the diagnosis is difficult, diagnostic laparoscopy and biopsy is very helpful. It is important to have an early diagnosis since delay in treatment can be detrimental in most cases.

Kikuchi-Fujimoto disease associated with systemic lupus erythematosus complicated with hemophagocytic lymphohistiocytosis: a case report.

BACKGROUND: Kikuchi-Fujimoto disease, which was originally described in young women, is a benign condition characterized by necrotizing lymphadenitis and fever. Even though the clinical course is usually self-limiting, it can be associated with recurrences and rarely can be associated with systemic lupus erythematosus or can be complicated with hemophagocytic lymphohistiocytosis. We report the case of a 17-year-old Sri Lankan Sinhalese schoolboy who presented with fever and cervical lymphadenopathy diagnosed as Kikuchi-Fujimoto disease and was complicated with hemophagocytic lymphohistiocytosis subsequently. Later he fulfilled the criteria for systemic lupus erythematosus. CASE PRESENTATION: A 17-year-old previously healthy Sinhalese schoolboy presented with high-grade fever associated with chills and rigors associated with loss of appetite and loss of weight for more than 40 days. On examination, he had bilateral firm matted tender cervical lymphadenopathy and firm hepatomegaly. An excision biopsy of his right cervical lymph node revealed necrotizing lymphadenitis and immunohistochemistry of a lymph node biopsy favored Kikuchi disease. Initial antinuclear antibody and anti-double-stranded deoxyribonucleic acid tests were negative and his C3 and C4 levels were normal. An infections screening was negative. He was treated with steroids. While in hospital he developed hemophagocytic lymphohistiocytosis and renal impairment. Later his antinuclear antibody titer became positive in 1:160 and fulfilled the diagnostic criteria for systemic lupus erythematosus. He was managed with steroids and immune suppressive drugs and showed remarkable improvement. CONCLUSION: Although Kikuchi-Fujimoto disease is uncommon in male patients, it needs to be considered in patients with lymphadenopathy and fever. The disease can be complicated with hemophagocytic lymphohistiocytosis and the patients need continuous monitoring for the possible development of systemic lupus erythematosus later in the course.

Ticagrelor-induced Angioedema After Percutaneous Coronary Intervention in a Patient with a History of Ischemic Stroke and Low Response to Clopidogrel: A Rare Dilemma.

Dual antiplatelet therapy (DAPT) is widely recognized as the mainstay of treatment after percutaneous coronary intervention (PCI). Premature discontinuation may pose a risk of in-stent thrombosis, acute myocardial infarction, and death. With the increased usage of antiplatelet agents, increased attention has been drawn to their potential allergic reactions. A 66-year-old male with a history of coronary artery disease and ischemic stroke was admitted with worsening severity angina for cardiac catheterization. He was on dual antiplatelet agents, clopidogrel, and aspirin prior to admission. He had PCI and a drug-eluting stent deployment to the culprit vessel. Due to low responsiveness to clopidogrel, he was started on ticagrelor, as prasugrel was contraindicated due to the history of ischemic stroke. A few hours after ticagrelor initiation, he developed shortness of breath, swelling of the throat and tongue, and was diagnosed with angioedema. He didn't have any prior reported history of allergy to any medications to the contrast medium or heparin. The offending medication, ticagrelor, was discontinued. He was managed with intravenous steroids and antihistamines. After the resolution of angioedema, he was discharged with double the dose of clopidogrel in addition to aspirin. The patient did not have any ischemic symptoms or coronary events for the following six-month period of follow-up. The case highlights a relatively rare side effect of ticagrelor. Health care providers should be vigilant about the angioedema following ticagrelor administration. In our patient, it was effectively managed by discontinuing the offending medication and the administration of steroids and histamine blockers. The recovery was prompt, without any serious untoward effects. The DAPT was changed to clopidogrel, double the conventional dose, in addition to aspirin.

Sensory neuronopathy complicating systemic lupus erythematosus: a case report.

INTRODUCTION: Systemic lupus erythematosus is a multi-system connective tissue disorder. Peripheral neuropathy is a known and underestimated complication in systemic lupus erythematosus. Ganglionopathy manifests when neuronal cell bodies in the dorsal root ganglion are involved. Autoimmune disorders are a known etiology, with systemic lupus erythematosus being a rare cause. CASE PRESENTATION: A 32-year-old South Asian woman presented with oral ulceration involving her lips following initiation of treatment for a febrile illness associated with dysuria. She had a history of progressively worsening numbness over a period of 4 months involving both the upper and lower limbs symmetrically while sparing the trunk. Her vibration sense was impaired, and her reflexes were diminished. For the past 4 years, she had had a bilateral, symmetrical, non-deforming arthritis involving the upper and lower limbs. Her anti-nuclear antibody and anti-double-stranded deoxyribonucleic acid status were positive. Although her anti-Ro antibodies were positive, she did not have clinical features suggestive of Sjögren syndrome. Nerve conduction studies revealed sensory neuronopathy. A diagnosis of systemic lupus erythematosus complicated by sensory neuronopathy was made. Treatment with intravenous immunoglobulin resulted in clinical and electrophysiological improvement. CONCLUSION: Peripheral neuropathy in systemic lupus erythematosus can, by itself, be a disabling feature. Nerve conduction studies should be considered when relevant. Neuropathy in systemic lupus erythematosus should be given greater recognition, and rarer forms of presentation should be entertained in the differential diagnosis when the clinical picture is atypical. Intravenous immunoglobulin may have role in treatment of sensory neuronopathy in systemic lupus erythematosus.