Purpose To describe an unusual case of Whipple’s disease (WD) complicated by uveitis, and subsequent paradoxical worsening after effective antibiotic treatment targeting Tropheryma whipplei (TW). Methods Case report. Results A 53-year-old male presented with bilateral knee arthritis, weight loss, chronic low-grade fever, and cognitive disorders. He was under treatment with tumor necrosis factor α inhibitors (TNFi) for seronegative spondyloarthritis. Given this unusual clinical presentation, further investigations were performed and revealed blood, saliva, stool, synovial fluid and cerebrospinal fluid positivity for TW, confirming the diagnosis of systemic WD. Ophthalmologic examination revealed bilateral posterior uveitis and an aqueous humor sample confirmed the presence of intraocular TW. TNFi were stopped, and the patient was subsequently treated with adequate antibiotics (ceftriaxone, followed by doxycycline and hydroxychloroquine), and subconjunctival corticosteroid injections. After a transient improvement of the ocular symptoms, he presented a recurrence of posterior segment inflammation, leading to repeated PCR testing for TW which were negative. Therefore, paradoxical worsening of the inflammation in the context of immune recovery uveitis (IRU) was thought to be the culprit. The patient was treated with systemic corticosteroid therapy, allowing for rapid improvement of the ocular findings. Conclusions This case underlines the possibility of IRU complicating WD. Ophthalmologists, rheumatologists, and internists should be aware of this rare complication, particularly in the context of previous immunosuppressive therapy.

Granulomatous myositis is a clinical-pathological entity, which has been rarely reported, mostly described in sarcoidosis. Currently, no clear and simple prognostic factor has been identified to predict granulomatous myositis evolution. The clinical, anatomopathological, imaging, and biological characteristics of 26 patients with granulomatous myositis were retrospectively collected to describe clinical presentation and outcomes of this condition. Twenty-six patients with granulomatous myositis were included (14 males) with a median age of symptom onset of 65 years. 54% of patients presented a severe form of the disease defined as a Rankin score ≥2 at last follow-up visit or a progressive form of the disease (no improvement under treatment). Etiology were sarcoidosis (n=14), inclusion body myositis (n=4), autoimmune disease (n=1), hematological malignancy (n=1), and idiopathic (n=6). Distal deficit and amyotrophy were more frequent among those with a severe disease. Corticosteroids led to improvement in 75% of cases, but 66% of responders relapsed. Methotrexate appeared as a promising second line therapy with clinical improvement in 50% of patients, and no relapse in responders. Granulomatous myositis is often a severe and difficult-to-treat disease in which patients frequently progress towards severe disability. The presence of muscle atrophy and distal weakness appears to be frequently associated with a severe form of the disease.

Diagnosis of histiocytosis can be difficult and one of the biggest challenges is to distinguish between reactive and neoplastic histiocytes on histology alone. Recently, OCT2 nuclear expression was reported in Rosai-Dorfman disease (RDD). Our purpose was to expand the testing of OCT2 on a broader variety of sporadic or H syndrome-related histiocytoses. Cases of histiocytoses were retrieved from the files of Ambroise Paré Pathology Department. All slides and molecular analyses were reviewed, and staining was completed with immunohistochemistry for OCT2. A total of 156 samples from different localizations were tested. Among sporadic cases, 52 patients had RDD, and 10 patients had mixed histiocytosis combining RDD with Erdheim Chester disease (ECD, n = 8), Langerhans cell histiocytosis (LCH, n = 2) or juvenile xanthogranuloma (JXG, n = 1). All these patients were positive for OCT2 in RDD characteristic histiocytes. Twenty-three patients had ECD and all but two (91

Sarcoidosis is a multisystemic disease characterized by non-caseating granuloma infiltrating various organs. The form with symptomatic muscular involvement is called muscular sarcoidosis. The impact of immune cells composing the granuloma on the skeletal muscle is misunderstood. Here, we investigated the granuloma–skeletal muscle interactions through spatial transcriptomics on two patients affected by muscular sarcoidosis. Five major transcriptomic clusters corresponding to perigranuloma, granuloma, and three successive muscle tissue areas (proximal, intermediate, and distal) around the granuloma were identified. Analyses revealed upregulated pathways in the granuloma corresponding to the activation of T-lymphocytes and monocytes/macrophages cytokines, the upregulation of extracellular matrix signatures, and the induction of the TGF-β signaling in the perigranuloma. A comparison between the proximal and distal muscles to the granuloma revealed an inverse correlation between the distance to the granuloma and the upregulation of cellular response to interferon-γ/α, TNF-α, IL-1,4,6, fibroblast proliferation, epithelial to mesenchymal cell transition, and the downregulation of muscle gene expression. These data shed light on the intercommunications between granulomas and the muscle tissue and provide pathophysiological mechanisms by showing that granuloma immune cells have a direct impact on proximal muscle tissue by promoting its progressive replacement by fibrosis via the expression of pro-inflammatory and profibrosing signatures. These data could possibly explain the evolution towards a state of disability for some patients.

A 33-year-old man was referred to our internal medicine department after an ophthalmic examination revealed a bilateral granulomatous anterior and intermediate uveitis with papillitis (figure A) associated with retinal dystrophy features (figure B). The patient had been experiencing decreased vision for several months and had a history of childhood-onset bilateral arthritis, involving proximal and distal inter pha lan geal and meta carpophalangeal joints. His sister, mother, and uncle were previously treated for idiopathic uveitis and papillitis. He reported recurrent headaches and anhidrosis. Physical examination revealed hand deformities (figure C) with nail dystrophy and melanonychia (figure D) and an enlarged spleen (20 cm). X-rays showed erosions of the proximal and distal interphalangeal joints (figure E). Laboratory investigations found elevated C-reactive protein

Abstract Background: Whipple's disease is a rare infectious systemic condition caused by Tropheryma whipplei which, can involve several organs such as the gastrointestinal tract, joins, skin, central nervous system, and eyes. Because of its non-specific symptoms and frequent join involvement preceding other Whipple's disease symptoms, a relevant percentage of patients are treated as inflammatory arthritis and received immunosuppressive treatment such as tumor necrosis factor α inhibitors, associated with Immune Reconstitution Inflammatory Syndrome (IRIS), complicating antibiotic therapy. Case presentation: A 53-year-old male presented with bilateral knee arthritis, a weight loss of 30 kg in 6 months without diarrhea, a chronic febricula at 38°C, and cognitive disorders. He was under treatment with tumor necrosis factor α for a misdiagnosis of presumed post-viral spondyloarthritis. Given the unusual clinical presentation for spondyloarthritis, further tests were performed as Polymerase Chain Reaction (PCR) in blood, saliva, stools, joint fluid of the left knee, and cerebrospinal fluid and revealing the presence of the T. whipplei genome, confirming the diagnosis of WD and antibiotic treatment was started. In addition, an ophthalmic examination revealed that the patient presented bilateral posterior uveitis and an aqueous humor sample confirmed the presence of T.whippley. Thus, the patient was treated with classical Whipple’s disease therapy and subconjunctival corticosteroid injections. At three months, he presented persistent ocular posterior segment inflammation, leading to repeated PCR tests in blood, saliva, cerebrospinal fluid, stools, and aqueous humor, which were negatives. Therefore, an ocular IRIS was considered in the context of posterior uveitis recurrence after the effectiveness of antibiotic therapy and negative samples. Thus, the patient was treated with systemic corticosteroid therapy, allowing ocular inflammatory signs to disappear in both eyes. Conclusions: This case revealed the existence of IRIS-induced uveitis complicating Whipple’s disease. Therefore, ophthalmologists, rheumatologists, and internists should be aware of this rare complication, particularly in the context of previous immunosuppressive therapy.

We describe the case of a woman in her 60s admitted to the intensive care unit after a first generalised tonic-clonic seizure in the context of alcohol withdrawal. She was placed under invasive mechanical ventilation due to persistence of coma despite antiepileptic treatment. Despite continuous sedation with propofol, the frequency and intensity of seizure increased. Seizures were very similar to epileptic tonic-clonic seizures and were recorded with video and electroencephalogram (EEG). A diagnosis of tetanus was considered after a scalp wound was discovered. The patient’s husband revealed that a trismus had appeared a few days before hospital admission after a head trauma. EEG showed a pattern of diffuse spikes, which disappeared after a cisatracurium bolus. The diagnosis of tetanus was later confirmed by cultures from wound samples. Therefore, severe tetanus can mimic both the clinical and EEG features of status epilepticus and could be added to the differential diagnosis of epilepsy.

Crystal Storing Histiocytosis and Bing Neel Syndrome are two diseases induced by paraprotein. Herein, we report a rare case of Crystal Storing Histiocytosis associated with Bing-Neel-like neurological manifestations in the context of marginal zone lymphoma with plasmacytic differentiation.