Rare Systemic Diseases Research Articles

NLRP1 mutations cause autoinflammatory diseases in human

Inflammation is a vital and complex process in response to diverse tissue damaging stimuli such as trauma, injury and pathogen. NLRP1, NLRP3 and NLRC4 belonging to the intracellular proteins Nod like receptor family, are capable of sensing the inflammatory inducers and trigger the assembly of a large complex called the inflammasome. By inducing the caspase-1 activation, inflammasome plays a crucial role in the release of IL-1β and IL-18, two critical cytokines of the initial steps of inflammatory responsesand, in some cases, the induction of a pro-inflammatory cell death called pyroptosis. Whereas mutations in NLRP3 and NLRC4 have been linked to two rare monogenic systemic autoinflammatory diseases (SAIDs), several polymorphisms in the NLRP1 gene have been associated extensively to an increased risk of autoimmune disorders (e.g. vitiligo, psoriasis, type 1 diabetes, and rheumatoid arthritis). We identified for the first time two distinct NLRP1 mutations in patients displaying a novel systemic autoinflammatory disease (SAID) and a novel syndrome combining autoinflammation and autoimmunity.

Epigenetics and Vasculitis: a Comprehensive Review.

Vasculitides represent a group of relatively rare systemic inflammatory diseases of the blood vessels. Despite recent progress in understanding the genetic basis and the underlying pathogenic mechanisms in vasculitis, the etiology and pathogenesis of vasculitis remain incompletely understood. Epigenetic dysregulation plays an important role in immune-mediated diseases, and the contribution of epigenetic aberrancies in vasculitis is increasingly being recognized. Histone modifications in the PR3 and MPO gene loci might be mechanistically involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Similarly, other studies revealed important epigenetic contribution to other vasculitides, including Kawasaki disease and IgA vasculitis. More recently, genome-wide epigenomic studies have been performed in several vasculitides. A recent genome-wide DNA methylation study uncovered an important role for epigenetic remodeling of cytoskeleton-related genes in the pathogenesis of Behçet's disease and suggested that reversal of some of these DNA methylation changes associates with disease remission. Genome-wide DNA methylation profiling characterized the inflammatory response in temporal artery tissue from patients with giant cell arteritis and showed increased activation of calcineurin/nuclear factor of activated T cells (NFAT) signaling, prompting the suggestion that a specific calcineurin/NFAT inhibitor that is well tolerated and with the added beneficial anti-platelet activity, such as dipyridamole, might be of therapeutic potential in giant cell arteritis. While epigenetic studies in systemic vasculitis are still in their infancy, currently available data clearly indicate that investigating the epigenetic mechanisms underlying these diseases will help to better understand the pathogenesis of vasculitis and provide novel targets for the development of disease biomarkers and new therapies.

Intervention des patients dans l’animation d’un programme d’éducation thérapeutique dédié au lupus systémique : définitions, mise en place et bénéfices

PurposeThough recommended, participation of patients with specific expertise in therapeutic education programs (TEP) is rare. This work reports the experience of a national reference centre for rare systemic diseases. Patients and methodsInvolvement of “expert patients” (EP) has been planned from the development of a TEP dedicated to systemic lupus: patients’ roles and required expertise have been defined and linked to the pedagogical tools. Such patients have been recruited during individual interviews and called to participate to specific pedagogical training. EP intervention have been evaluated by questionnaire to EP and health care providers. ResultsThree EP's functions have been identified: sharing experiences, giving “tips and tricks” and promoting dialogue. EP's interventions has been organised into a hierarchy (from sharing to co-animation). Among 298 patients enrolled in the TEP, 25 (8.4%) have been identified as possible EP. Eight of them (32%) benefited from a specific training of 12 hours. Among these patients, two (25%) regularly participate to the education sessions. For EP as well as for health care providers, EP's intervention seems beneficial (visual scale scores of 7.5 and 9.5, respectively). ConclusionsThough difficult to organise, EP's intervention in TEP dedicated to rare systemic diseases seems useful and would earn to be increase.

Cutaneous manifestations of systemic autoinflammatory disorders

Rare systemic autoinflammatory diseases (sAIDs) are driven by cytokine-mediated uncontrolled inflammation that results from activation of innate immune pathways. sAIDs present with recurrent fever episodes, fatigue, musculoskeletal symptoms, gastrointestinal, neurologic, and skin manifestations. They include hereditary monogenic and acquired multifactorial disorders, show a significant morbidity and usually persist for life. Due to the limited awareness of sAIDs, they are often associated with a considerable delay in diagnosis. Within the last decade, the use of cytokine-neutralizing therapies has been shown to improve the clinical symptoms of many patients with different sAIDs. Because skin involvement, such as urticarial, pustular, or ulcerative eruptions, is common in a variety of autoinflammatory disorders, dermatologists should be aware of the most important diseases and their skin phenotypes. This review gives an overview on prototype sAIDs with focus on cutaneous manifestations, clinical clues, and diagnostic approaches. Effective treatment options, such as anti–interleukin-1–targeted therapies, are discussed.

Oral manifestations of phosphatase and tensin homolog hamartoma tumor syndrome: A report of three cases

Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) encompasses several rare disorders linked to mutations of the PTEN gene, including Cowden disease (CD) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). The authors present a case series involving patients with characteristic periodontal features. The authors assessed three patients, two of whom already had been diagnosed with BRRS: a 60-year-old man and his 33-year-old daughter, both of whom had pathognomonic oral and cutaneous manifestations, and a 26-year-old man affected by multiple micropapillomatous and keratotic periodontal lesions, through which the diagnosis of CD was made. All three patients were referred to the oral medicine unit of the authors' institution because of asymptomatic lesions of the oral mucosa, and two of them underwent incisional biopsy. This series of cases emphasizes that oral health care workers always should perform a more careful visual inspection of the oral cavity without neglecting a macroscopic analysis of the gingival pattern. The knowledge of these diseases and their clinical features, associated with a multidisciplinary approach, allows clinicians to achieve remarkable diagnostic success. Gingival manifestations may represent one of the primary clinically detectable manifestations of these rare systemic diseases, in respect of which an early diagnosis could decrease the associated mortality and morbidity.

ŠIRDIES AL AMILOIDOZĖ: KLINIKINIO ATVEJO APRAŠYMAS

Amiloidozė – tai grupė retų sisteminių ligų, kurioms būdingas sutrikęs baltyminių struktūrų susidarymas ir fibrilių formavimasis. Amiloidozės atsiradimą lemia didelis amiloido pirmtako kiekis organizme, nevisiškas amiloido pirmtako suirimas makrofagų sistemoje bei tam tikri audinių ypatumai. Nors liga sukelia sisteminius pakitimus, tačiau amiloido depozicijos laipsnis įvairiuose organuose skiriasi ir lemia skirtingas klinikines amiloidozės išraiškas. Širdies amiloidozė – tai klinikinis susikaupusio amiloido širdyje pasireiškimas. Širdies amiloidozės metu pagrindinis patogenezinis elementas – intersticinė amiloido infiltracija, sukelianti infiltracinę kardiomiopatiją, kuri progresuoja iki restrikcinės kardiomiopatijos ir širdies nepakankamumo. Širdies pažeidimas amiloidozės metu lemia itin blogą prognozę ir didelį mirštamumą. Todėl labai svarbu kuo ankstyvesnė diagnostika, kuri užkirstų kelią amiloido depozicijai įvairiuose organuose. Vis dėlto širdies amiloidozės diagnostika dažnai būna atlikta procesui esant toli pažengus, nes nėra specifinio klinikinio ligos pasireiškimo, todėl instrumentiniai tyrimai, patvirtinantys ligos diagnozę, atliekami per vėlai. Pagrindinis amiloidozės gydymas nukreiptas į infiltracinio proceso sustabdymą, kurio metu siekiama blokuoti amiloido depoziciją įvairiuose organuose ir į amiloidozės sukeltų komplikacijų gydymą, kuris mažina simptomus ir pagerina bendrą paciento būklę.

A58: Demographics, Clinical Features and Therapies of Patients with Juvenile Dermatomyositis Participating in a National Myositis Patient Registry

Background/Purpose:The myositis syndromes are rare systemic autoimmune diseases with poorly understood etiologies. We present the demographics, illness features and treatments of patients with juvenile dermatomyositis (JDM) who enrolled in a newly created national registry.Methods:Using a patient database from The Myositis Association and supplemental advertisements, a national registry of myositis patients was established. Between December 2010 and July 2012 questionnaires were mailed to 8847 myositis patients in the US and Canada. The questionnaire queried demographics, clinical features, environmental exposures, and quality of life. Descriptive statistics and multivariable logistic regression analysis were computed using GraphPad Prysm and SAS.Results:1956 patients (22%) returned the questionnaire and consented to participate; 1806 who met probable or definite Bohan and Peter criteria for myositis were included (708 DM, 483 PM, 466 IBM, 139 JDM, 10 JPM); juvenile patients were diagnosed before age 18 years. Of the 139 JDM patients, the median age at diagnosis was 6.9 years and median disease duration at enrollment was 10.3 years. Most JDM patients were female (78%) and Non‐Hispanic Caucasian (88%), and the remainder were Hispanic (6.5%), Asian (2.9%), multiple races (2.2%), and Black (0.7%). Patients or their parents often completed a graduate degree (23%) or college degree (29%). JDM patients were primarily diagnosed by a pediatric rheumatologist (48%), with adult and pediatric dermatologists (22%), pediatric neurologists and primary care physicians (11% each) diagnosing most of the remaining patients; 67% were under the care of a pediatric rheumatologist. JDM patients frequently had skin rashes as a major manifestation (86%); arthritis (35%) and dysphagia (32%) were also common, whereas lung disease (12%) was less frequent. An additional autoimmune disease was present in 18% of JDM patients, with JIA (8%) and SLE and celiac disease (3% each) the most frequent. There were no recorded associated malignancies. 98% of JDM patients received prednisone therapy. Methotrexate was the most common steroid‐sparing agent (84%), followed by hydroxychloroquine (60%), IV pulse solumedrol (54%), IVIG (48%), cyclosporine (19%), rituximab and anti‐TNFs (10% each). Predictors of which agents were received varied among medications, but included age, year of JDM diagnosis, gender, and region of country. Pulse solumedrol and cyclosporine were more likely to be used in JDM patients with dysphagia, hydroxychloroquine in patients with skin rashes and less likely in those with fevers, and azathioprine was less likely in patients with arthritis. Of medications utilized, 45% of JDM patients reported responding best to IVIG, 39% responded best to prednisone, 33% to anti‐TNFs, and 29% to cyclophosphamide.Conclusion:A nationwide myositis registry has been established and includes a subsample of JDM patients that appears demographically and clinically representative of other US populations. This registry may help identify environmental exposures associated with myositis, elucidate factors associated with quality of life, and serve as an important resource for future clinical investigations.

Cardiovascular Magnetic Resonance in Rare Systemic Diseases

The heart may be involved in a number of systemic syndromes. The pericardium, myocardium, heart valves, and coronary arteries may be involved either singly or in various combinations. In most cases the cardiac manifestations are not the dominant feature, but in some it is the primary determinant of symptoms and survival. Both the early identification of cardiac involvement and the etiology underneath is of paramount importance, as some causes require specific treatment and may be correctable. In this respect non-invasive imaging plays a central role especially in the context of rare cardiac disease, where specific imaging features can help to make the appropriate diagnosis on a substantial proportion of them, enabling the physician to choose the best management strategy tailored to the disease. Whereas echocardiography is the firstline investigation for detecting a cardiac involvement in systemic disease, cardiovascular magnetic resonance (CMR) provides additional incremental data allowing in addition to a detailed examination of cardiac structure and function also the tissue characterization. The aim of this review is therefore to delineate the role of CMR in detecting cardiac involvement in patients with rare systemic diseases and delineate the specific imaging features of the different etiologies.

Genitourinary Small-Cell Carcinoma: A Single-Institution Experience

Small-cell carcinomas (sccs) of the genitourinary (gu) tract are rare systemic diseases, and there is no standard treatment strategy for patients with this malignancy. The objectives of the present study were to report the management and outcome of patients with scc of the gu tract treated at a tertiary-care institution from 1982 to 2009. In a chart review of all patients diagnosed with scc of the gu tract between 1982 and 2009, data on demographics, clinical and pathologic characteristics, treatment, and patient outcomes were collected. The 58 patients identified had scc in the following primary sites: urinary bladder (n = 35), prostate (n = 17), and upper urinary tract (n = 6). In 38 patients (66%), the scc was of pure histology; in the remainder, histology was mixed. Overall, 28 patients had limited-stage disease; 24 had extensive-stage disease; and staging was unknown in 6 patients. Median survival for the entire cohort was 7.5 months, with extensive-stage disease being identified as a poor prognostic factor (survival was 22.0 months for limited-stage patients and 4.1 months for extensive-stage patients, p < 0.001). Based on site, prostate patients fared worst, with a median survival of only 5.1 months. Compared with best supportive care, treatment was associated with better outcomes (median survival: 12.3 months vs. 2.3 months, p < 0.0001). Small-cell cancer of the gu tract is an aggressive cancer, with a poor prognosis overall. Although there is no standard of care, patients should be treated using a multimodality approach analogous to that used in the treatment of small-cell lung cancer.

AB0846 Smoking and alcohol consumption may increase the development of anti-jo-1 antibodies in patients with idiopathic inflammatory myopathies

BackgroundIdiopathic Inflammatory Myopathies (IIMs) are a group of rare systemic autoimmune diseases, characterized by chronic inflammation of the muscle, resulting symmetric proximal weakness, characteristic rashes and other systemic features. The...

Лімфангіолейоміоматоз легень і спонтанний пневмохілоторакс

Lymphangioleiomyomatosis occupies a special place among rare systemic diseases of lungs, which are manifested by respiratory failure and the gradual development of pulmonary heart. Manifestations of the pleural cavity in the form of pneumothorax and pleural effusion syndrome are characteristic for the disease. In order to verify the process, the authors recommend a study of pleural punctate with Sudan-III for detection of lymph and a CT-scanning after removal of the contents of the pleural cavity. “Cell” pattern of lungs in combination with chylothorax confirm the diagnosis of lymphangioleiomyomatosis. In particularly complex cases, in their opinion, the lung and pleura bi-opsy is required.

Tratamiento de mantenimiento en las vasculitis asociadas a anticuerpos contra citoplasma de neutrófilos (ANCA)

ANCA-associated vasculitides are rare and complex systemic diseases. Collaborative studies in both Europe and the United States of America have been particularly important in the development of randomized clinical trials that have studied the safety of maintenance therapy for these diseases. Although cyclophosphamide continues to be the main drug utilized during induction therapy, its long-term side effects have given rise to the study of other immunosuppressive drugs for the maintenance phase. We herein review these studies with particular attention to combination therapy and the duration of treatment.

Measures of adult and juvenile dermatomyositis, polymyositis, and inclusion body myositis: Physician and Patient/Parent Global Activity, Manual Muscle Testing (MMT), Health Assessment Questionnaire (HAQ)/Childhood Health Assessment Questionnaire (C‐HAQ), Childhood Myositis Assessment Scale (CMAS), Myositis Disease Activity Assessment Tool (MDAAT), Disease Activity Score (DAS), Short Form 36 (SF‐36), Child Health Questionnaire (CHQ), Physician Global Damage, Myositis Damage Index (MDI), Quantitative Muscle

The idiopathic inflammatory myopathies, including adult and juvenile dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM), are rare systemic autoimmune diseases that are characterized by chronic proximal muscle inflammation and weakness. In previous decades, there were few commonly used outcome measures in myositis, and those outcome measures were not validated. Thus, in the past the assessment of outcomes in therapeutic trials was focused on non-standardized measurement of muscle strength and function only. Over the last decade, however, two international collaborative groups, the International Myositis Assessment and Clinical Studies Group (IMACS) and the Paediatric Rheumatology International Trials Organisation (PRINTO), have defined consensus core set measures to assess myositis disease activity and damage in adults and children and have begun to validate and standardize these measures (1;2). IMACS and PRINTO have also developed preliminary definitions of improvement, which can be used as outcomes for therapeutic trials. These response criteria combine the core set activity measures to determine clinically meaningful improvement (3;4). Our section on myositis assessment focuses first on these core set measures of disease activity, quality of life (which is part of the PRINTO core set of activity, but a separate assessment domain for IMACS), and disease damage. To date, most of the validation data available for these core set measures are in patients with juvenile DM, with more limited validation in adult patients with DM or PM. Despite these efforts, there are still important gaps in validation of these core set measures, and no validation studies have yet been performed in patients with IBM, although they are now being used frequently in myositis therapeutic trials. We end the chapter with tools that have been used primarily in research studies and a few therapeutic trials, which have some supporting validation in certain subgroups of patients with myositis. These tools are primarily organ-specific measures, including strength and functional assessments and cutaneous assessment tools. Quantitative muscle testing and the IBM Functional Rating Scale are the most commonly used instruments to assess patients with IBM, and although they have little supporting validation in myositis, quantitative muscle testing has been well validated in other myopathies and has been used frequently as an endpoint in therapeutic trials for IBM. Although the methods for the assessment of myositis patients have been limited in their scope, great strides have been made in the last decade in the development of new partially validated tools (see Table 1) and international multidisciplinary consensus in using these measures that should enhance our understanding of the diverse effects of myositis on many organ systems and the development of new therapies. Table 1 Summary of Measures of Disease Activity in Myositis Physician and Patient/Parent Global Activity General Description Purpose An overall rating of the disease activity related to myositis, defined as potentially reversible pathology or physiology resulting from the underlying disease process (1).

コルヒチンが有効であった再発性多発性軟骨炎の１例

Relapsing polychyondritis (RP) is a comparatively rare systemic diseases that is manifested by relapses of painful inflammation to the cartilage tissue of the whole body, especially pinna, the nose and the trachea. It is suspected to be an autoimmune disease because various autologous such as type 2 collagen are admitted although details of the etiology are uncertain.We report a case of 26-year-old woman who had severe subglottic stenosis due to relapsing polychondritis. The stenosis was getting so severe that we had to perform a tracheostomy. At the time of inflammation exacerbation, we had to increase the steroid dosage. It was considered that we should be able to reduce the increase in steroid dosage by treating the RP with colchine.

Trends in dermatomyositis- and polymyositis-related mortality in the state of São Paulo, Brazil, 1985-2007: multiple cause-of-death analysis.

BackgroundDermatomyositis (DM) and polymyositis (PM) are rare systemic autoimmune rheumatic diseases with high fatality rates. There have been few population-based mortality studies of dermatomyositis and polymyositis in the world, and none have been conducted in Brazil. The objective of the present study was to employ multiple-cause-of-death methodology in the analysis of trends in mortality related to dermatomyositis and polymyositis in the state of São Paulo, Brazil, between 1985 and 2007.MethodsWe analyzed mortality data from the São Paulo State Data Analysis System, selecting all death certificates on which DM or PM was listed as a cause of death. The variables sex, age and underlying, associated or total mentions of causes of death were studied using mortality rates, proportions and historical trends. Statistical analysis were performed by chi-square and H Kruskal-Wallis tests, variance analysis and linear regression. A p value less than 0.05 was regarded as significant.ResultsOver a 23-year period, there were 318 DM-related deaths and 316 PM-related deaths. Overall, DM/PM was designated as an underlying cause in 55.2% and as an associated cause in 44.8%; among 634 total deaths females accounted for 71.5%. During the study period, age- and gender-adjusted DM mortality rates did not change significantly, although PM as an underlying cause and total mentions of PM trended lower (p < 0.05). The mean ages at death were 47.76 ± 20.81 years for DM and 54.24 ± 17.94 years for PM (p = 0.0003). For DM/PM, respectively, as underlying causes, the principal associated causes of death were as follows: pneumonia (in 43.8%/33.5%); respiratory failure (in 34.4%/32.3%); interstitial pulmonary diseases and other pulmonary conditions (in 28.9%/17.6%); and septicemia (in 22.8%/15.9%). For DM/PM, respectively, as associated causes, the following were the principal underlying causes of death: respiratory disorders (in 28.3%/26.0%); circulatory disorders (in 17.4%/20.5%); neoplasms (in 16.7%/13.7%); infectious and parasitic diseases (in 11.6%/9.6%); and gastrointestinal disorders (in 8.0%/4.8%). Of the 318 DM-related deaths, 36 involved neoplasms, compared with 20 of the 316 PM-related deaths (p = 0.03).ConclusionsOur study using multiple cause of deaths found that DM/PM were identified as the underlying cause of death in only 55.2% of the deaths, indicating that both diseases were underestimated in the primary mortality statistics. We observed a predominance of deaths in women and in older individuals, as well as a trend toward stability in the mortality rates. We have confirmed that the risk of death is greater when either disease is accompanied by neoplasm, albeit to lesser degree in individuals with PM. The investigation of the underlying and associated causes of death related to DM/PM broaden the knowledge of the natural history of both diseases and could help integrate mortality data for use in the evaluation of control measures for DM/PM.

Juvenile idiopatiske inflammatoriske myopatier

Juvenile idiopathic inflammatory myopathies (JIIM) is a group of rare autoimmune systemic diseases in children and adolescents, characterized by chronic skeletal muscle inflammation. Unlike in adults, dermatomyositis (JDM) is by far the most common of the idiopathic inflammatory myopathies in children and adolescents. The hallmark of JDM is calcinosis, lipodystrophy and vasculitis, findings that differs the juvenile form of dermatomyosits from the adult form. JDM is still diagnosed and classified by Bohan and Peter’s criteria from 1975. There are limited data on long time outcome of this disease

Self-assembly of Bacteriophage-associated Hyaluronate Lyase (HYLP2) into an Enzymatically Active Fibrillar Film

The in vitro assembly of a soluble protein into its mature fibrillar form is usually accompanied by loss of its functional activity. Our study is the first demonstration of a natural enzyme (HylP2) retaining its enzymatic activity on conversion from pre-fibril to mature fibril and supports the contention that minor conformational changes in the native folded form of a protein can lead to the formation of a functional fibril. Hyaluronate lyase (HylP2) is a natural enzyme of bacteriophage 10403 of Streptococcus pyogenes. At pH 5.0, the enzyme undergoes partial unfolding localized in its N-terminal domain while the C-terminal domain maintains its folded trimeric conformation. This structural variant of HylP2 retains about 70% enzymatic activity with hyaluronan. It further self-assembles into a fibrillar film in vitro through solvent-exposed nonpolar surfaces and intermolecular beta-sheet formation by the beta-strands in the protein. Interestingly, the mature fibrillar film of HylP2 also retains about 60 and 20% enzymatic activity for hyaluronic acid and chondroitin sulfate, respectively. The possession of broad substrate specificity by the fibrillar form of HylP2 indicates that fluctuations in pH, which do not lead to loss of functionality of HylP2, might assist in bacterial pathogenesis. The formation of fibrillar film-like structure has been observed for the first time among the hyaluronidase enzymes. After acquiring this film-like structure in bacteriophage, HylP2 still retains its enzymatic activity, which establishes that these fibrils are a genuinely acquired protein fold/structure.

Review of the classification and assessment of the cutaneous manifestations of the idiopathic inflammatory myopathies

Adult and juvenile dermatomyositis, polymyositis and myositis overlapping with another connective tissue disease are rare systemic autoimmune diseases with a primary feature of weakness and muscle inflammation. Cutaneous findings specific to the underlying condition are present in many patients with these disorders. Some lesions are highly characteristic of the idiopathic inflammatory myopathies (IIM), especially in dermatomyositis. Some cutaneous findings are common but not specific to the IIM and others are less frequently observed in patients with these illnesses. Many of these manifestations also have different grades of disease activity or damage. This photoessay reviews the classification and assessment of the cutaneous manifestations of the IIM and presents example photographs of many of the lesions of adult and juvenile IIM accumulated from the clinical experience of international experts in these conditions. The purpose of this work is to facilitate better recognition of the diverse cutaneous manifestations associated with these inflammatory myopathies.

Photoessay of the cutaneous manifestations of the idiopathic inflammatory myopathies

Adult and juvenile dermatomyositis, polymyositis and myositis overlapping with another connective tissue disease are rare systemic autoimmune diseases with a primary feature of weakness and muscle inflammation. Cutaneous findings specific to the underlying condition are present in many patients with these disorders. Some lesions are highly characteristic of the idiopathic inflammatory myopathies (IIM), especially in dermatomyositis. Some cutaneous findings are common but not specific to the IIM and others are less frequently observed in patients with these illnesses. Many of these manifestations also have different grades of disease activity or damage. This photoessay reviews the classification and assessment of the cutaneous manifestations of the IIM and presents example photographs of many of the lesions of adult and juvenile IIM accumulated from the clinical experience of international experts in these conditions. The purpose of this work is to facilitate better recognition of the diverse cutaneous manifestations associated with these inflammatory myopathies.

Morbus Whipple mit normaler Dünndarmhistologie bei ankylosierender Spondylitis

A 33-year-old woman with increasing back pain was referred to our hospital 8 years ago. As she had ankylosing sacroilitis and peripheral arthritis she was diagnosed as having ankolysing spondylitis with involvement of the peripheral joints. She recently developed persistent diarrhea, abdominal symptoms and weight loss.Laboratory findings revealed a chronic inflammatory disease. Infection of the gastrointestinal tract was excluded. Duodenal biopsy was normal on PAS staining, Tropheryma whipplei-DNA was detected by the polymerase chain reaction (PCR).Initially the patient was treated for 6 months with diclofenac and ibuprofen without improvement of her condition. As the spondylitis persisted, she was given anti-TNF-alpha treatment 7 years after the onset of symptoms. When Whipple's disease was diagnosed this treatment was stopped and antibiotics (ceftriaxone) was started and then continued with co-trimoxazole for one year with significantly improvement in her condition.In patients presenting with symptoms involving several organs, rare systemic diseases should be considered. If symptoms are typical of Whipple's disease, but duodenal biopsies are negative on PAS staining, a sensitive PCR assay may detect T. whipplei-DNA confirming this infection. Appropriate antibiotic treatment can then be initiated.