Underlying Autoimmune Condition Research Articles

Severe acquired Factor VII deficiency complicating an aplastic anemia, successfully treated with corticosteroids.

Factor VII deficiency is a rare hemostatic disorder that can lead to severe clinical outcomes. Due to the scarcity of reported cases, treatment guidelines for this condition remain unclear. In this report, we present a case of acquired factor VII deficiency (aFVII) in an elderly female with medullary aplasia. The initial clinical manifestation was hemarthrosis, accompanied by a rapid increase in prothrombin time. Prompt intervention involved supplementation to address the deficiency. Subsequent laboratory testing failed to detect any specific factor VII inhibitor. Considering the patient's frailty, immunosuppressive therapy comprising only corticosteroids was administered. The potential triggering mechanisms may include recurrent episodes of sepsis or an underlying autoimmune condition. Further research is necessary to better understand the etiology and optimal management of aFVII deficiency.

Risk and Outcomes of Hospitalizations in Patients with Anti-Phospholipid Syndrome Admitted with Autoimmune Hemolytic Anemia: A Nation-Wide Analysis

Introduction: Autoimmune hemolytic anemia (AIHA) can occur as a primary disorder or as a secondary manifestation of an underlying autoimmune condition. The coexistence of anti-phospholipid syndrome (APS) and AIHA can be very complex and challenging to manage given the intertwining of the prothrombotic and hemolytic states. In this study, we explored the outcomes of underlying antiphospholipid syndrome in autoimmune hemolytic anemia hospitalizations. Method: The National Inpatient Sample (NIS) database was queried using the International Classification of Diseases (ICD) codes to identify hospitalizations for AIHA and then the data was subclassified into hospitalizations with and without APS. Demographics, comorbidities, and outcomes were identified using appropriate ICD 9/10 codes. Propensity score matched cohorts were generated for APS status and adjusted for age, race, sex, smoking, obesity, DM, CHF, CKD/ESRD, and liver disease. Results: A total of 7,609 AIHA hospitalizations were included, with 76 patients having underlying APS and 7,533 did not have APS. Mean age was younger in the APS cohort and there were also more females, blacks and Hispanics compared to the non-APS cohort. Propensity score matching was used to generate two cohorts, adjusting for age, race, sex, and for co-morbidities including obesity, smoking, DM, CHF, CKD/ESRD and liver disease. The adjusted analysis showed an 8.59 times higher risk of developing venous thromboembolic events (VTE) in AIHA with APS as compared to those hospitalizations without APS (Odds ratio (OR): 8.59, CI: 1.05-70.5; p=0.03). There was also a statistically significant increase in mean hospitalization cost in the APS group (p=0.001). A trend towards more arterial athero-embolic events (AAE), major bleeding events, and AKI as well as longer length of stay was seen in hospitalizations with APS, but it did not reach statistical significance. No significant difference in in-hospital mortality was seen between the two groups. The results are summarized in the Figure 1. Conclusion: APS confers additional risk to AIHA hospitalizations with significantly higher VTE events and added costs. Further studies should address the complex management of anticoagulation and prothrombotic risk in APS in the setting of active hemolytic anemia.

Invasive Fungal Infection of the Duramater as the Presenting Manifestation of Disseminated Sarcoidosis (P10-10.005)

<h3>Objective:</h3> To describe a case of invasive fungal infection of the duramater which was the presenting manifestation of Disseminated sarcoidosis <h3>Background:</h3> Invasive Central nervous system fungal infections are usually encountered in the setting of immunosuppressive conditions, craniospinal trauma or instrumentation. It is rare for a treatment naïve patient with sarcoidosis to develop fungal infection of the duramater. <h3>Design/Methods:</h3> We describe the case of a young male who was found to have nodular thickening of the duramater due to Invasive CNS fungal infection. <h3>Results:</h3> We had a 27 year old man who had no prior comorbidities who presented with a single seizure. On evaluation, he was found to have nodular thickening of the Duramater. Differentials of infective, inflammatory, histiocytic and malignant conditions were considered. He underwent detailed evaluation and PET-CT revealed generalized lymphadenopathy. Biopsy from the dural thickening revealed septate hyphae and fungal culture showed Acremonium species. There were granulomas found on histopathologic examination of the dural as well as subcarinal lymphnode biopsy. He was treated with Voriconazole for 24 weeks followed by treatment of sarcoidosis. <h3>Conclusions:</h3> Sarcoidosis may be associated with immunodeficiency due to its effects on the lymphocytes, bone marrow and other organs such as the thymus. There have been several reports of patients with sarcoidosis being predisposed to infections such as Progressive multifocal leukoencephalopathy, fungal infections, tuberculosis and other bacterial infections. These infections may occur de-novo in the absence of immunosuppressant drugs or corticosteroids which have been traditionally used in the management of sarcoidosis with organ threatening or life threatening symptoms. Infections that occur as the first manifestation of an underlying autoimmune condition are challenging to diagnose. Appropriate diagnosis is essential to ensure optimum treatment of both conditions. <b>Disclosure:</b> Dr. Elavarasi has stock in Pfizer. Dr. Elavarasi has stock in PGHL. The institution of Dr. Elavarasi has received research support from All India Institute of Medical Sciences, New Delhi. The institution of Dr. Elavarasi has received research support from Indian Council for Medical Research. Dr. SINGH has nothing to disclose. Dr. CHHATTERPAL has nothing to disclose. Dr. Wig has nothing to disclose. Dr. Mittal has nothing to disclose. Mehar Chand Sharma has nothing to disclose. Dr. DAS has nothing to disclose. Ajay Garg has nothing to disclose. Dr. Jagdevan has nothing to disclose. Dr. Shamim has nothing to disclose. Dr. Tripathi has nothing to disclose. Dr. Vibha has nothing to disclose. Rajesh Kumar Singh has nothing to disclose.

E028 Seronegative arthritis in the context of CHIP: is this a new entity that needs further investigation?

Abstract Background/Aims We describe a seronegative, non-erosive arthritis in the context of clonal haematopoiesis of indeterminant potential (CHIP), the premalignant stage of most myeloid malignancies and myelodysplastic syndromes (MDS). The use of targeted next-generation sequencing (NGS) has helped the clinician to identify the high risk individuals who are at an increased risk of haematological malignancies. Patients presenting with persistent neutropenia and inflammatory arthritis in addition to bone marrow examination, these genomic sequencing should be considered to identify clonal cytopenia and the risk for progression to myeloid malignancies. Methods A 70-year-old man referred to rheumatology clinic with pain and swelling in the small joints of the hands along with shoulder, hip and knee pains. There were few psoriatic patches but no typical features of psoriatic arthropathy. Clinically he had evidence of synovitis in the MCP joints, high inflammatory markers (CRP 157) and a low neutrophil count. Bone marrow examination at time of initial review was reported as completely normal as there was no evidence of MDS and the neutropenia was attributed to his underlying autoimmune condition. His X-rays showed no evidence of erosions and USS scan confirmed synovitis in the MCP joints. He was RF and anti-CCP negative and the diagnosis of suspected seronegative RA was considered. He was initially treated with steroids and hydroxychloroquine but the symptoms relapsed while tapering dose of steroids. A year later, adalimumab was introduced to manage the inflammatory arthritis. He did not show much response to it and golimumab was started, to which he responded very well. He was maintaining excellent clinical remission for 3 years however the neutropenia worsened. He was referred back to haematology for further investigations. Results The neutrophil counts had been fluctuating between 0.3 and 0.9 while receiving golimumab. Slight improvement in the count was noted after taking a 6-month break from biologics. However, this improvement was very transient. A repeat BM biopsy including myeloid next-generation genomic sequencing which diagnosed a high-risk CHIP/clinical cytopenia of unknown significance (CCUS) (mutation profile: IDH 1 R132 (12%VAF), IDH2 R140 (36% VAF), SRSF2 P95 (47% VAF) with no morphological evidence of MDS. Since this is a premalignant condition and there is a significant risk of developing AML, a decision was taken to stop golimumab and start rituximab. The neutrophil count has increased from 0.36 to 1.89 after starting the rituximab and the inflammatory arthritis remains in remission. Conclusion This case highlights low threshold of suspicion of CHIP in patients presenting with features of inflammatory arthritis and neutropenia and/or other cytopenias. Thus, detailed bone marrow sampling including targeted myeloid NGS panels should be undertaken to exclude CHIP or CCUS. This will potentially help us to guide treatment. Disclosure S. Mohamed: None. T. McKerrell: None. D. Makkuni: None.

28-Year-Old Man With Recurrent Vertigo, Syncope, and Progressive Memory Impairment

28-Year-Old Man With Recurrent Vertigo, Syncope, and Progressive Memory Impairment

Inflammation at the Tissue-Electrode Interface in a Case of Rapid Deterioration in Hearing Performance Leading to Explant After Cochlear Implantation

The reasons for soft failure after cochlear implantation require investigation. This study proposes a method to study and characterize the tissue response to the array in a case of soft failure in a person undergoing reimplantation. The woman in her 50s, with an underlying autoimmune condition, received a cochlear implant using hearing preservation technique after developing profound hearing loss more than 2 kHz with a moderate loss of less than 500 Hz over a 10-year period. The case was identified as a soft failure due to deteriorating performance, discomfort, and migration over the 10 months after implantation. Impedance telemetry, speech perception measures, and audiometric thresholds are described. At explantation there was evidence of fibrosis. To use histology and immunohistochemistry to determine the cellular response of the tissue associated with the electrode array at time of explantation. Identification of the cell types, regional variations, and inflammatory marker expression in the fibrotic tissue associated with the array. Neutrophils and eosinophils were identified, along with a variable pattern of collagen deposition. CD68 and CD163-positive macrophages and T cells were variably distributed through the tissue and interleukin-1 beta and vascular endothelial growth factor receptor-2 expression was identified. The expression profile is evidence of active inflammation in the tissue despite the time since implantation. This study is the first to characterize the tissue response to the array in a person undergoing reimplantation, and who can be followed to determine the individual response to arrays. It establishes that the investigation of explanted devices after soft-failure is feasible.

TB myositis in a patient with dermatomyositis post immunosuppression

55-year-old African female with a history of initially refractory TIF1-y antibody positive dermatomyositis, with progressive proximal muscle weakness with difficulty swallowing, requiring regular inpatient admissions with the administration of IV steroids and IVIG. The patient was started on immunosuppression with mycophenolate as a steroid sparing agent. The patient slowly improved after initiation of immunosuppression, with a significant reduction in her rash, weakness, and dysphagia. After a few months of therapy, the patient noted pain in the right axilla and proximal right lower extremity with swelling and pain limiting her mobility. There was a concern for underlying malignancy for which PET scan was done, which showed hypermetabolic edema and swelling of musculature involving right thigh, right pectoral minor and left scapularis consistent with infectious or inflammatory myositis. Concern for focal dermatomyositis was raised and the patient received pulse IV steroids over 5 days with initial improvement. The patient later developed fevers, night sweats and chills, for which the patient was seen in ED. Initial vitals were concerning for sepsis, due to which patient was started on broad-spectrum antibiotics. CT scan of the chest and right lower extremity were done which showed, no pulmonary infiltrates, 5 cm right pectoralis minor and 9.4 cm right gluteus minimus fluid collection consistent with abscess.Interventional radiology was consulted, and abscesses were aspirated, aspirate from chest wall was positive acid-fast bacilli, concerning for mycobacterium. Cultures were sent to the health department and were noted to be positive for TB. At this time, it was noted that the patient had a prior diagnosis of latent TB when she moved to the United States. The patient was started on Myambutol, Nydrazid, Levaquin, Rifampin, and Bactrim.Tuberculous infections continue to be one of the deadliest infections around the world, with a significantly low incidence rate (2.8/100000) as compared to developing countries. Even with a low incidence rate, there is always a concern for reactivation of latent TB with the initiation of immunosuppression. Tb myositis is one of rare presentation and that can be difficult with diagnosis, especially in a patient who has an underlying autoimmune condition that could have a similar presentation. We recommend getting prior workup to rule out tuberculosis prior to the initiation of immunosuppression.

Immune related adverse effects (IRAEs) in patients with cancer who received immune checkpoint inhibitors (ICIs): A single center experience from rural Maine.

e19265 Background: ICIs are used for a variety of malignancies and have shown to improve survival, but they are associated with IRAEs. We aim to identify the frequency and severity of new IRAEs and flares of preexisting autoimmune (AI) disorders excluding thyroid disorders in cancer patients treated with ICIs at our institution. Methods: We conducted a retrospective chart review analysis of all cancer patients who received ICIs: nivolumab, pembrolizumab, atezolizumab and durvalumab at the Northern Light Cancer Institute from June 2015 to March 2019. We excluded patients who received ipilimumab. We then studied those who developed IRAEs. Results: Out of 465 who received ICIs, 115(24.7%) developed IRAEs. 83 out of 298 (27.9%) nivolumab recipients, 20/121 (15.7%) pembrolizumab recipients, 5/26 (19.2%) atezolizumab and 7/20 (35%) durvalumab recipients developed IRAEs. Some patients had multiple toxicities. Median age at cancer diagnosis was 66 years, evenly split among males and females. Majority (63%) were treated for Lung cancer, followed by melanoma (20%) and genitourinary cancers (12%). Summary of new IRAEs are as noted in the table below. In patients with new IRAEs treatment was held in 29(6%) for a median duration of 7.2 wks. Upon rechallenge with the same ICI in 27 patients, 20(74%) tolerated and 7 did not leading to permanent discontinuation. Majority were treated with steroids and some required immunomodulators. Interestingly 39(8%) patients with underlying AI condition received ICIs. Of these 11(28.2%) developed flares, resulting in permanent discontinuation of drug in 4. The majority tolerated the treatment well. Treatment was permanently discontinued in 70(15%), 26(6%) required hospital admission for IRAEs. Pneumonitis was the most common toxicity necessitating treatment discontinuation and hospital stay. Conclusions: In real world setting the frequency and severity of IRAEs was more than the reported literature data, leading to higher rates of permanent discontinuation of treatment. [Table: see text]

21. Sepsis?

IntroductionSepsis is a major cause of mortality and there have been many patient safety initiatives to improve the outcome such as ‘Think Sepsis’ and ‘Sepsis 6’. It is essential to consider mimics of sepsis in those presenting with fever, particularly when there is no improvement despite antimicrobials. Macrophage activation syndrome (MAS) is a complication of uncontrolled inflammation from underlying connective tissue disease resulting in a sepsis-like condition. Delay to the detection and treatment of this condition can also result in significant morbidity and mortality.Case descriptionWe report a 28-year-old female presenting with shortness of breath, chest pain, bilateral leg swelling and fevers. Relevant past medical history included a recent diagnosis of Graves’ disease for which she had been commenced on carbimazole. On presentation CRP 53 mg/L and d-dimer 14100, chest X-ray; cardiomegally and bilateral pleural effusions, CT thoracic aorta angiogram; large pericardial effusion with maximum depth 5.9cm and compression of the cardiac chambers. Echocardiogram; preserved ejection fraction of 55-60%. The patient was commenced on intravenous antibiotics, furosemide and pericardial drain removed 1.5L. The patient was referred to the rheumatology team on day 10. She reported episodic arthralgia, recurrent mouth ulcers, anaemia; with no evidence of haemolysis and pericardial effusion (serositis). Serology; ANA 1:1280 fine speckled pattern, dsDNA > 200, ENA positive (RNP and Smith antibodies) and low complement; C3 (0.35) and C4 (0.005), ferritin 1400, CRP 40 and ESR 62; consistent with a diagnosis of systemic lupus erythematosus (SLE). The patient was pulsed with IV methylprednisolone 500mg on Day 13 and started on prednisolone 40mg and azathioprine.Day 16; the patient developed a new pyrexia and profound hypotension resulting in admission to intensive care unit for inotropic support and escalation of antibiotics. Bedside echo revealed a small volume pericardial fluid; no tamponade, but significant new biventricular failure. Repeat ferritin was 8489, Triglycerides 5.5, LDH 331. The patient had persistent fevers and blood dyscrasias consistent with macrophage activation syndrome (MAS) with lupus myocarditis. The patient was pulsed with a further two doses of IV methylprednisolone 750mg and commenced on ciclosporin 3mg/kg.Day 18; the patient became increasingly tachycardic with increasing oxygen demands and a worsening metabolic acidosis despite renal replacement therapy. Based on the rapidity of deterioration, and lack of response to intervention the patient was transferred for extracorporeal membrane oxygenation (ECMO).DiscussionThis case was of interest due to the diagnostic difficulties the team faced as an underlying autoimmune condition was not initially considered. Distinguishing the need for antibiotics versus immunosuppression can be daunting for general medical teams. This case highlights the importance of involving rheumatology early in the course of a patient presenting with fever not responding to conventional therapies. Lupus myocarditis was confirmed by cardiac biopsy after the patient went into cardiogenic shock with a LVEF 10% due to lupus myocarditis requiring ECMO support showing the severity of disease activity. The use of ECMO remains rare in our practice and there are only five centres within the UK offering this service.The patient has made an excellent response to treatment and is well maintained on mycophenolate mofetil and hydroxychloroquine; most recent echocardiogram May 2018 shows resolved effusion with normal biventricular size, ejection fraction 50 to 55%.Key learning pointsMAS secondary to underlying rheumatic and connective tissue disease can present with fever and features that mimic sepsis. An awareness of MAS is needed as early diagnosis and prompt initial treatment are both key factors for a favourable outcome. This case resulted in a change to clinical practice. A Trust-wide guideline on the management of MAS has now been produced to guide teams on the management of MAS in the patient with sepsis who is not improving. This case also shows the importance of collaborative team working (physicians, ICU, tertiary centre).Conflicts of interestThe authors have declared no conflicts of interest.

SUN-285 Autoimmune Brain Disease Associated with Severe Obesity and Progressive Hypothalamic and Pituitary Dysfunction

Hypothalamic dysfunction can lead to rapidly progressive severe obesity, which has been observed in the pediatric age group after an insult to the hypothalamus, such as tumors, trauma, inflammatory disease, or surgical treatment. We present here the progression of hypothalamic and pituitary dysfunction associated with severe obesity due to a primary inflammatory process in the brain and the therapeutic effect of immunosuppressants and aggressive weight management. The patient presented with new onset focal epilepsy refractory to anti-epileptic medications at age 6 years 8 months (illness month 0) at 23.6 kg and BMI-Z of -0.07. At month 2, he had a 2 kg weight gain thought to be due to anti-epileptics. At month 7 (35.6 kg, BMI-Z 2.10), he had gained 12 kg, precocious puberty was noted and he was started on a GnRH agonist. He was also having behavioral changes, including decreased cognition, hyperphagia, and difficulty sleeping. At month 10 (45.5 kg, BMI-Z 2.57), a brain biopsy showing lymphocytic infiltration confirmed the primary diagnosis of autoimmune brain disease as the cause of hypothalamic dysfunction and seizure disorder; therefore, a methylprednisone burst was started at month 11 (48.2 kg, BMI-Z 2.63), followed by monthly cyclophosphamide and a 7 month oral prednisone taper. By month 12, he developed respiratory symptoms requiring hospital admission. Indirect calorimetry revealed resting energy expenditure of 802 kcal/day; topiramate was initiated, and he was discharged home on a 1200 kcal/day diet. At month 13, central hypothyroidism was diagnosed (TSH 0.34, free T4 0.61) and levothyroxine started. At month 13.5, he was at maximum weight (60.1 kg, BMI-Z 2.88, 36.5 kg total gain) and he again had worsened respiratory distress requiring admission; at this time phentermine was started, CPAP was initiated, diet was decreased to 1000 kcal/day and changed to ketogenic. From months 13 to 18, he had his first weight reduction of 5.5 kg with a noted decrease in appetite. He was continued on monthly cyclophosphamide and IV methylprednisone through month 16 when a brain MRI was showed improvement; cyclophosphamide discontinued and prednisone weaned. Adrenal insufficiency was found, although it was unclear if iatrogenic or central. By month 19 (57.1 kg, BMI-Z 2.73) off immunosuppression, he had worsened hyperphagia and seizure activity and decreased cognitive abilities, possibly suggestive of a flare of the brain inflammation; thus aggressive immunosuppression was reinitiated. This case demonstrates severe obesity related to progressive hypothalamic and pituitary dysfunction secondary to inflammatory brain disease. The management of weight gain for this patient remains difficult due to hyperphagia related to behavior dysregulation and low basal metabolic rate, in addition to continued need for immunosuppressants to treat the underlying autoimmune condition. Funding: NIDDK K23

Autoimmune vertigo: an update on vestibular disorders associated with autoimmune mechanisms.

The role of the immune system in mediating cochleovestibular pathologies has received increasing attention in recent years. Autoimmune vertigo may be an invalidating condition and may worsen the quality of life of affected patients, especially in the cases of delayed diagnosis. Since the etiopathogenesis is still not clear, also the treatment is not yet completely delineated. According to the clinical presentation, autoimmune vertigo can present as an isolated disorder or in association with systemic autoimmune diseases. The main feature in autoimmune vertigo is the presence of an abnormal immune response, in either absence or presence of systemic autoimmune disease, directed against delicate components of the inner ear. This may determine a functional or anatomical alteration, with an inflammatory reaction often devastating for hearing and balance. Being the exact pathogenesis unknown, the diagnosis of autoimmune vertigo is based either on clinical criteria or on a positive response to steroids. The earlier the diagnosis is made, the sooner the therapy can be installed, giving a chance to the recovery of inner ear damages. Corticosteroids represent the most effective and universally accepted treatment, even if other immunomodulatory drugs are now having a more extensive use. HIGHLIGHTS: Vertigo is relatively frequent in autoimmune diseases; however, it is often misdiagnosed or attributed to central nervous system alterations rather to specific inner ear involvement. Vertigo and other audiovestibular symptoms may be the first manifestation of an autoimmune disease and if correctly addressed could significantly contribute to early diagnosis of the underlying autoimmune disease. Early diagnosis of immune-related vertigo can lead to prompt initiation of targeted therapy with elevate chances of preventing irreversible damages to the inner ear. The presence of alternating phases of well-being and disabling symptoms in patients with vertigo should always been considered, as they could suggest an underlying autoimmune condition.

Use of PD-1 pathway inhibitors among patients with non-small cell lung cancer (NSCLC) and preexisting autoimmune disorders.

9081 Background: Since patients (pts) with NSCLC and autoimmune (AI) disease were largely excluded from immune checkpoint inhibitor clinical trials, we aimed to determine the safety of PD-1 inhibitors in NSCLC pts with a history of AI diseases. Methods: As part of a multi-center, retrospective study, we collected clinicopathologic data from pts with advanced stage IIIB or stage IV NSCLC with a history of AI disease and who received treatment with a PD-1 inhibitor as monotherapy. Qualifying AI disorders included but were not limited to: thyroiditis (excluding hypothyroidism without clear autoimmune etiology), inflammatory bowel disease, as well as rheumatologic, neurologic and dermatologic conditions. Results: We identified 46 pts with NSCLC treated with a PD-1 inhibitor who also had a history of AI disease. At the time of PD-1 inhibitor treatment initiation, 13% of pts had active AI symptoms and 19% were receiving immunomodulatory agents for their AI condition. The median period of follow up after initiation of anti-PD-1 therapy was 17.4 weeks (range 0.6-72.1 weeks). Exacerbation of the underlying AI condition occurred in 8 pts (17%). Two of these pts required steroid treatment (both for rheumatoid arthritis), and three of these pts required temporary interruption of treatment due AI disease flare. Overall, twelve (26%) pts developed at least one immune-related adverse event (irAE) unrelated to the underlying AI condition (8 grade 1-2, 4 grade 3); there were no cases of grade 4-5 irAEs. PD-1 therapy was permanently discontinued in 3 cases due to the development of an irAE (1 for grade 1 pneumonitis, 1 for grade 3 transaminitis, 1 for grade 3 diabetes insipidus). Conclusions: In pts with NSCLC and a history of AI conditions treated with PD-1 blockade, symptomatic flare of underlying AI disease was uncommon. The rate of immune-related toxicities in this population appears similar to published studies in pts without baseline AI conditions. Further analysis of pts with active AI conditions is needed to clarify the safety profile in this population.

Handy Hints About Raynaud's Phenomenon in Children: A Critical Review.

Raynaud's phenomenon (RP) is a vasospastic disorder characterized by recurrent self-limited episodes of skin pallor, cyanosis, and hyperemia caused by paroxysmal spasms in the small arteries of the fingers and toes and can occur in any age group. Hands, feet, nose, ears, and nipples can be affected. The diagnosis is made clinically, assessing varying degrees of ischemia in the involved areas of skin, but this transient ischemia may also herald the onset of connective tissue disease. Investigation is recommended when RP starts in childhood to exclude an underlying autoimmune condition and close follow-up for its development. Management of RP in children includes conservative and pharmacologic treatments.

Autoantibodies in Neuropsychiatric Disorders.

Little is known about the etiology of neuropsychiatric disorders. The identification of autoantibodies targeting the N-methyl-d-aspartate receptor (NMDA-R), which causes neurological and psychiatric symptoms, has reinvigorated the hypothesis that other patient subgroups may also suffer from an underlying autoimmune condition. In recent years, a wide range of neuropsychiatric diseases and autoantibodies targeting ion-channels or neuronal receptors including NMDA-R, voltage gated potassium channel complex (VGKC complex), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R), γ-aminobutyric acid receptor (GABA-R) and dopamine receptor (DR) were studied and conflicting reports have been published regarding the seroprevalence of these autoantibodies. A clear causative role of autoantibodies on psychiatric symptoms has as yet only been shown for the NMDA-R. Several other autoantibodies have been related to the presence of certain symptoms and antibody effector mechanisms have been proposed. However, extensive clinical studies with large multicenter efforts to standardize diagnostic procedures for autoimmune etiology and animal studies are needed to confirm the pathogenicity of these autoantibodies. In this review, we discuss the current knowledge of neuronal autoantibodies in the major neuropsychiatric disorders: psychotic, major depression, autism spectrum, obsessive-compulsive and attention-deficit/hyperactivity disorders.

Life-threatening colitis and complete response with ipilimumab in a patient with metastatic BRAF-mutant melanoma and rheumatoid arthritis

Immune checkpoint inhibitors, such as ipilimumab (an anti-CTLA4 antibody), have become a commonly used therapy in cancer. To date, safety data of patients with underlying autoimmune disease is limited. We present a case of a patient with rheumatoid arthritis who was diagnosed of a BRAF-mutant metastatic melanoma. The patient was treated with ipilimumab and presented with high-grade colitis requiring immunosuppressors. Despite of the immune-related adverse event, no exacerbation of the rheumatoid arthritis was observed and the patient achieved a complete response. This case report contributes to the scarce literature on the use of immune checkpoint inhibitors in patients with an underlying autoimmune condition.

Graves' Disease, Hypoparathyroidism, Systemic Lupus Erythematosus, Alopecia, and Angioedema: Autoimmune Polyglandular Syndrome Variant or Coincidence?

Data on coexisting Graves' disease (GD), hypoparathyroidism, and systemic lupus erythematosus (SLE) are limited. The thyroid and parathyroid glands may be extra sensitive to irradiation damage in an underlying autoimmune condition. A 34-year-old black woman presented with tetanic-like cramps, easy skin bruising, fatigue, weight gain, nocturia and back pain. She was previously diagnosed with GD in 2001 and underwent radioiodine therapy (RAI) in 9/01 using 6 mCi. PostRAI (November 2001) she developed hypocalcemia and hypothyroidism (2/02). In 2007, SLE was diagnosed. In October 2009, s-calcium and PTH were still low at 7.1 mg/dl and 9 pg/mL, respectively, although the patient denied symptoms on vitamin D and calcium supplementation. To identify possible autoimmune damage of the parathyroids, we evaluated the presence of activating antibodies to the CaSR and also analyzed the DNA sequence of all 6 translated exons and flanking intronic sequences of her CaSR gene for a functionally significant CaSR mutation but neither was positive. The initial autoimmune damage to her thyroid and possibly parathyroid glands followed by irradiation of them seems to have contributed to her developing both hypoparathyroidism (11/01) and hypothyroidism (2002). The patient could potentially have had parathyroid autoantibodies in 2001 that disappeared by 2009 when she was tested for them. We consider that the multiple autoimmune conditions developed over the past decade of her life with the concurrent irradiation contributing to her brittle hypoparathyroidism. Select patients with GD and perhaps parathyroid autoantibodies with a slowly developing destructive impact on the parathyroid glands may then develop overt hyoparathyroidism with rather low dose RAI ablation. This patient adds to the evolving spectrum of polyglandular syndrome variants.

Post-partum pituitary insufficiency and livedo reticularis presenting a diagnostic challenge in a resource limited setting in Tanzania: a case report, clinical discussion and brief review of existing literature

BackgroundPituitary disorders following pregnancy are an important yet under reported clinical entity in the developing world. Conversely, post partum panhypopituitarism has a more devastating impact on women in such settings due to high fertility rates, poor obstetric care and scarcity of diagnostic and therapeutic resources available.Case presentationA 37 year old African female presented ten years post partum with features of multiple endocrine deficiencies including hypothyroidism, hypoadrenalism, lactation failure and secondary amenorrhea. In addition she had clinical features of an underlying autoimmune condition. These included a history of post-partum thyroiditis, alopecia areata, livedo reticularis and deranged coagulation indices. A remarkable clinical response followed appropriate hormone replacement therapy including steroids. This constellation has never been reported before; we therefore present an interesting clinical discussion including a brief review of existing literature.ConclusionPost partum pituitary insufficiency is an under-reported condition of immense clinical importance especially in the developing world. A high clinical index of suspicion is vital to ensure an early and correct diagnosis which will have a direct bearing on management and patient outcome.

Influence of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone on serologic parameters and clinical course in lymphoma patients with autoimmune diseases

As patients with B-cell lymphomas suffering from an underlying autoimmune condition undergoing therapy with the CD20 antibody rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) offer the unique possibility of monitoring effects of therapy on various rheumatologic parameters, we have evaluated serologic autoimmune markers and the clinical outcome of patients with autoimmune diseases (ADs) who received lymphoma treatment with R-CHOP during the course of their disease. We have retrospectively analysed 13 patients with non-Hodgkin's lymphoma who concurrently suffered from ADs and were treated with the R-CHOP regimen. Subjective parameters along with rheumatoid factor (RF) and antinuclear antibodies (ANA) were serially measured. The median levels of RF were 901 IU/ml [inter-quartile-range (IQR) 189-2520] before and 75 IU/ml (IQR 45-644) after therapy (P = 0.028). The median levels of ANA were 800 (IQR 140-2560) before and 100 (40-1280) after therapy (P = 0.027). Ten (77%) patients showed clinical improvement of their autoimmune symptoms, two (15%) reported no difference and one (7%) patient with rheumatoid arthritis-related worsening symptoms during therapy with R-CHOP. The autoimmune-related symptoms recurred after a median time of 7 weeks (IQR 6-8) in seven patients. In terms of lymphoma response, 11 patients achieved a complete remission and two a partial remission. This analysis indicates that R-CHOP given for lymphoma treatment is also effective for therapy of concurrent rheumatoid diseases. Both rheumatoid parameters as well as clinical symptoms showed a significant decrease during treatment with this immunochemotherapy. The effects on the rheumatic diseases, however, seem to be of limited duration.

Early Cancer of the Stomach Arising after Successful Treatment of Gastric MALT Lymphoma in Patients with Autoimmune Disease

Background: Extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma) arises in lymphoid tissue acquired through chronic antigenic stimulation as exemplified by Helicobacter pylori. Secondary development of gastric cancer, however, is thought to be a rare event. The detection of a signet ring cell carcinoma during follow-up endoscopy after successful therapy of MALT lymphoma in a patient with Sjogren's syndrome prompted us to analyse the frequency of subsequent gastric cancer in patients with underlying autoimmune disease (AD). Methods: Patients with early stage MALT lymphoma and an underlying AD were evaluated for the occurrence of a secondary gastric cancer during the course of follow-up. Data analysed included the type of AD, stage of MALT lymphoma, H. pylori status, treatment for MALT lymphoma and response, follow-up, the presence of a secondary cancer, and time to development of cancer. In all patients, histologic samples were reassessed for the extent of gastritis, presence of intestinal metaplasia or focal atrophy at the time of lymphoma diagnosis. Results: A total of eight patients with overt AD at the time of diagnosis of MALT lymphoma were identified. All patients were women aged between 56 and 77 years; 5 had Sjogren's syndrome, 2 had autoimmune thyroiditis (1 along with psoriasis) and 1 suffered from polymyalgia rheumatica. All patients had early stage MALT lymphoma restricted to the mucosa and submucosa at the time of diagnosis, and the presence of H. pylori was found in all cases. Two of these patients achieved complete remission (CR) of the lymphoma following H. pylori eradication, while six were judged unresponsive and underwent chemotherapy, resulting in CR in all cases. One patient died from stroke while being in CR for 2 months following chemotherapy. Two patients (25%) developed early cancer limited to the gastric mucosa while being in CR from lymphoma for 9 and 27 months, respectively, and underwent partial gastrectomy. Final staging of gastric cancer revealed pTlpNOMO in both cases. Of the remaining 5 cases, 1 patient had a local lymphoma relapse 18 months after CR and was salvaged with radiotherapy. In the remaining 4 patients, no evidence of lymphoma recurrence or a second malignancy has been found so far by regular follow-up every 3 months for a time-span between 52 and 63 months after initial diagnosis. Conclusion: Patients with concurrent MALT lymphoma and an underlying autoimmune condition show not only an impaired response to H. pylori eradication but might also be at increased risk for the development of gastric cancer. In view of this, such patients should be followed closely by regular endoscopies after remission of MALT lymphoma.