Jochen Wacker

Detection of periarticular urate deposits with dual energy CT in patients with acute gouty arthritis

The gold standard for establishing the diagnosis of gouty arthritis is the detection of monosodium urate (MSU) crystals in synovial fluid or periarticular tophi. The European League Against Rheumatism recommendations from 2006 state that ‘for typical presentations of gout a clinical diagnosis alone is reasonably accurate but not definitive without crystal confirmation’.1 In addition, various imaging methods can help to non-invasively support the diagnosis of gout. Joint ultrasonography can detect MSU deposits at cartilaginous surfaces (‘double contour sign’) as well as periarticular tophus formation.2 3 Dual energy CT (DECT) is an imaging method that uses x-ray beams of two different energies to differentiate MSU deposits from connective tissues and from calcium containing structures by their absorption properties.4 Choi et al have demonstrated that in tophaceous gout, DECT …

Clinical Images: Hippokrates confirmed by positron emission tomography.

2006;45:269–73. 27. Siebert S, Amos N, Fielding CA, Wang EC, Aksentijevich I, Williams BD, et al. Reduced tumor necrosis factor signaling in primary human fibroblasts containing a tumor necrosis factor receptor superfamily 1A mutant. Arthritis Rheum 2005;52: 1287–92. 28. Rebelo SL, Bainbridge SE, Amel-Kashipaz MR, Radford PM, Powell RJ, Todd I, et al. Modeling of tumor necrosis factor receptor superfamily 1A mutants associated with tumor necrosis factor receptor–associated periodic syndrome indicates misfolding consistent with abnormal function. Arthritis Rheum 2006;54: 2674–87. 29. Lobito AA, Kimberley FC, Muppidi JR, Komarow H, Jackson AJ, Hull KM, et al. Abnormal disulfide-linked oligomerization results in ER retention and altered signaling by TNFR1 mutants in TNFR1-associated periodic fever syndrome (TRAPS). Blood 2006;108:1320–7. 30. Simon A, Park H, Maddipati R, Lobito AA, Bulua AC, Jackson AJ, et al. Concerted action of wild-type and mutant TNF receptors enhances inflammation in TNF receptor 1-associated periodic fever syndrome. Proc Natl Acad Sci U S A 2010;107:9801–6.

Response to: the value of 18(F)-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) and inflammation of unknown origin (IUO): data from a prospective study

Background Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostically challenging conditions. Diagnosis of underlying disease may be improved by 18F-fluorodesoxyglucose positron emission tomography (18F-FDG-PET). Methods Prospective study to test diagnostic utility of 18F-FDG-PET/CT in a large cohort of patients with FUO or IUO and to define parameters that increase the likelihood of diagnostic 18F-FDG-PET/CT. Patients with FUO or IUO received 18F-FDG-PET/CT scanning in addition to standard diagnostic work-up. 18F-FDG-PET/CT results were classified as helpful or non-helpful in establishing final diagnosis. Binary logistic regression was used to identify clinical parameters associated with a diagnostic 18F-FDG-PET/CT. Results 240 patients were enrolled, 72 with FUO, 142 with IUO and 26 had FUO or IUO previously (exFUO/IUO). Diagnosis was established in 190 patients (79.2%). The leading diagnoses were adult-onset Still’s disease (15.3%) in the FUO group, large vessel vasculitis (21.1%) and polymyalgia rheumatica (18.3%) in the IUO group and IgG4-related disease (15.4%) in the exFUO/IUO group. In 136 patients (56.7% of all patients and 71.6% of patients with a diagnosis), 18F-FDG-PET/CT was positive and helpful in finding the diagnosis. Predictive markers for a diagnostic 18F-FDG-PET/CT were age over 50 years (p=0.019), C-reactive protein (CRP) level over 30 mg/L (p=0.002) and absence of fever (p=0.001). Conclusion 18F-FDG-PET/CT scanning is helpful in ascertaining the correct diagnosis in more than 50% of the cases presenting with FUO and IUO. Absence of intermittent fever, higher age and elevated CRP level increase the likelihood for a diagnostic 18F-FDG-PET/CT.

[Hypertrophic osteoarthropathy. Bamberger-Marie disease].

Hypertrophic osteoarthropathy (HOA) is the classical neoplastic disease in rheumatology characterized by a combination of digital clubbing, joint and bone pain, and proliferative periostitis. This combination of symptoms should initiate an intensive search for an underlying malignant disease usually of thoracic organs. Here we report the case of a patient with HOA and neuroendocrine carcinoma of the esophagus. Other non-malignant disorders of the lungs, heart and other organs should be considered in the differential diagnosis. In addition, rare cases of a primary hereditary form of HOA exist and the genetic background has recently been discovered. Thus, new insights into the pathophysiology have improved diagnostic and therapeutic options for this disorder.ZusammenfassungDie hypertrophe Osteoarthropathie (HOA) ist die klassische paraneoplastische Erkrankung in der Rheumatologie, charakterisiert durch die Trias aus Trommelschlegelfingern mit Uhrglasnägeln, Gelenk- und Knochenschmerzen sowie proliferativer Periostitis. Diese Konstellation sollte Anlass zu einer intensiven Tumorsuche sein, wobei in der Regel intrathorakale Malignome zugrunde liegen. Wir berichten hier über einen Patienten mit HOA im Rahmen eines neuroendokrinen Ösophaguskarzinoms. Differenzialdiagnostisch kommen eine Reihe anderer nichtmaligner Erkrankungen der Lunge, des Herzens oder anderer Organe in Frage. Selten tritt auch eine primäre, familiäre Form der HOA auf, deren genetischer Hintergrund vor Kurzem entschlüsselt wurde. Neue Erkenntnisse zur Pathophysiologie dieser Erkrankung haben auch zu einer Erweiterung der diagnostischen und therapeutischen Möglichkeiten geführt.AbstractHypertrophic osteoarthropathy (HOA) is the classical neoplastic disease in rheumatology characterized by a combination of digital clubbing, joint and bone pain, and proliferative periostitis. This combination of symptoms should initiate an intensive search for an underlying malignant disease usually of thoracic organs. Here we report the case of a patient with HOA and neuroendocrine carcinoma of the esophagus. Other non-malignant disorders of the lungs, heart and other organs should be considered in the differential diagnosis. In addition, rare cases of a primary hereditary form of HOA exist and the genetic background has recently been discovered. Thus, new insights into the pathophysiology have improved diagnostic and therapeutic options for this disorder.

A Multiplex Kindred with Hennekam Syndrome due to Homozygosity for a CCBE1 Mutation that does not Prevent Protein Expression

Collagen and calcium-binding EGF domain-containing protein 1 (CCBE1) bi-allelic mutations have been associated with syndromes of widespread congenital lymphatic dysplasia, including Hennekam Syndrome (HS). HS is characterized by lymphedema, lymphangiectasia, and intellectual disability. CCBE1 encodes a putative extracellular matrix protein but the HS-causing mutations have not been studied biochemically. We report two HS siblings, born to consanguineous parents of Turkish ancestry, whose clinical phenotype also includes protein losing enteropathy, painful relapsing chylous ascites, and hypogammaglobulinemia. We identified by whole exome and Sanger sequencing the homozygous CCBE1 C174Y mutation in both siblings. This mutation had been previously reported in another HS kindred from the Netherlands. In over-expression studies, we found increased intracellular expression of all forms (monomers, dimers, trimers) of the CCBE1 C174Y mutant protein, by Western blot, despite mutant mRNA levels similar to wild-type (WT). In addition, we detected increased secretion of the mutant CCBE1 protein by ELISA. We further found the mutant and WT proteins to be evenly distributed in the cytoplasm, by immunofluorescence and confocal microscopy. Finally, we found a strong decrease of lymphatic vessels, with a corresponding diminished expression of CCBE1, by immunohistochemistry of the patients’ intestinal biopsies. In contrast, mucosal blood vessels and muscularis mucosae showed normal CCBE1 staining. Our findings show that the mutant CCBE1 C174Y protein is not loss-of-function by loss-of-expression.

Sudden visual loss in a patient with microscopic polyangiitis

ASSUNTA C. H. HO, NATHAN HASSON, DAVINDER SINGH-GREWAL Rheumatology Unit, Great Ormond Street Hospital for Children NHS Trust, London, UK, Department of Paediatrics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong, Department of Rheumatology, The Children’s Hospital at Westmead and Discipline of Paediatrics and Child Health, University of Sydney, Sydney, Australia Accepted 18 May 2009 Correspondence to: Assunta C. H. Ho, Department of Paediatrics, 6/F, Clinical Science Building, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong. E-mail: assuntaho@cuhk.edu.hk

In vivo detection of mucosal healing-involved histiocytes by confocal laser endomicroscopy

Histiocytes have a pivotal role in wound repair and intestinal epithelial recovery - the most important goal to sustain gut functionality. Yet, an in vivo description of colonic histiocytes by confocal laser endomicroscopy (CLE) is missing. Here, we report the case of a 45-years-old male patient who was referred to our clinic with weight loss and a history of two consecutive Clostridium difficile colitis episodes, the latter cured 3 wk before present admission. Stool microbiology was negative. Conventional colonoscopy showed atrophy and a light mucosal oedema in the distal colon. During on-going endoscopy, we performed a fluorescein-aided CLE which revealed large polygonal (histiocytes-like) cells with copious cytoplasm and large nuclei in the lamina propria of the sigmoid colon as well as regenerative epithelial changes. Histopathological assessment of biopsies from the same areas confirmed the endomicroscopical findings: Periodic acid-Schiff- and CD68-positive foamy histiocytes in the colonic lamina propria and an advanced epithelial recovery. Since stool microbiology was repeatedly negative and polymerase chain reaction-analysis from colonic biopsies could not detect any mRNA for Thropheryma whippleii and common pathogens, we interpreted this particular setting as a mucosal healing process after consecutive Clostridium difficile infections. In conclusion, by describing these colonic histiocytes, we highlight the clinical usefulness of CLE in describing the entity of histiocytes in vivo and in real-time during the process of post-infectious mucosal healing in the colon.

Diarrhoea and massive duodenal round cell infiltration in a 27-year-old HIV positive female

A 27-year-old black female with recently diagnosed HIV infection (CD4+ T cells 9/μl; viral load >106 copies/ml) was admitted to the hospital with diarrhoea, malaise, weight loss and ‘heavy legs’. On clinical examination, the emaciated patient (body mass index 15.8) was in a compromised clinical condition with bilateral ankle oedema. Laboratory tests revealed several pathological values including low albumen 15 g/l (reference level: 34–48) and severe pancytopenia (haemoglobin 4.5 g/dl, reference 12–16; white blood cell count (WBC) 3.6/nl, reference 4–10, platelet count (PLT, 61/nl, reference 140–400). Mean corpuscular volume (MCV, 80.2 fl) was at the lower limit of the reference level (80–99). Upper gastrointestinal endoscopy showed a striking picture …

Scurvy. A rare differential diagnosis of rheumatic diseases

BACKGROUND In December 2014 a patient presented to our clinic with the clinical symptoms of vasculitis. However, treatment with glucocorticoids did not lead to any improvement; therefore, the differential diagnostics were extended to other indications and ultimately led to the diagnosis of scurvy. OBJECTIVE This article describes the clinical picture of scurvy and its relationship to rheumatic diseases based on a clinical case and additional information from the literature. Differences and similarities with important rheumatological disease symptoms are presented. RESULTS Scurvy is a rare hypovitaminosis disease which can be manifested in different forms. In addition to vasculitis the symptoms can also resemble arthritis and hemarthrosis is a typical finding. These symptoms can be accompanied by unspecific manifestations, such as muscle pain and due to impaired collagen synthesis characteristic features, such as corkscrew hair can be observed. The causal therapy of scurvy is substitution of ascorbic acid. CONCLUSION Scurvy is a rare differential diagnosis in the context of rheumatic diseases. The indications for scurvy can be a lack of response to immunosuppressive and immunomodulatory drugs as well as individual symptoms, such as corkscrew hair.

Hypertrophe OsteoarthropathieHypertrophic osteoarthropathy

Hypertrophic osteoarthropathy (HOA) is the classical neoplastic disease in rheumatology characterized by a combination of digital clubbing, joint and bone pain, and proliferative periostitis. This combination of symptoms should initiate an intensive search for an underlying malignant disease usually of thoracic organs. Here we report the case of a patient with HOA and neuroendocrine carcinoma of the esophagus. Other non-malignant disorders of the lungs, heart and other organs should be considered in the differential diagnosis. In addition, rare cases of a primary hereditary form of HOA exist and the genetic background has recently been discovered. Thus, new insights into the pathophysiology have improved diagnostic and therapeutic options for this disorder.ZusammenfassungDie hypertrophe Osteoarthropathie (HOA) ist die klassische paraneoplastische Erkrankung in der Rheumatologie, charakterisiert durch die Trias aus Trommelschlegelfingern mit Uhrglasnägeln, Gelenk- und Knochenschmerzen sowie proliferativer Periostitis. Diese Konstellation sollte Anlass zu einer intensiven Tumorsuche sein, wobei in der Regel intrathorakale Malignome zugrunde liegen. Wir berichten hier über einen Patienten mit HOA im Rahmen eines neuroendokrinen Ösophaguskarzinoms. Differenzialdiagnostisch kommen eine Reihe anderer nichtmaligner Erkrankungen der Lunge, des Herzens oder anderer Organe in Frage. Selten tritt auch eine primäre, familiäre Form der HOA auf, deren genetischer Hintergrund vor Kurzem entschlüsselt wurde. Neue Erkenntnisse zur Pathophysiologie dieser Erkrankung haben auch zu einer Erweiterung der diagnostischen und therapeutischen Möglichkeiten geführt.AbstractHypertrophic osteoarthropathy (HOA) is the classical neoplastic disease in rheumatology characterized by a combination of digital clubbing, joint and bone pain, and proliferative periostitis. This combination of symptoms should initiate an intensive search for an underlying malignant disease usually of thoracic organs. Here we report the case of a patient with HOA and neuroendocrine carcinoma of the esophagus. Other non-malignant disorders of the lungs, heart and other organs should be considered in the differential diagnosis. In addition, rare cases of a primary hereditary form of HOA exist and the genetic background has recently been discovered. Thus, new insights into the pathophysiology have improved diagnostic and therapeutic options for this disorder.