Multiparametric autoantibody analysis: a new paradigm for the diagnosis of connective tissue diseases.

BACKGROUND: In patients affected by connective tissue diseases (CTDs), the identification of wide autoantibody profiles may prove useful in early diagnosis, in the evaluation of prognosis (risk stratification), and in predicting response to therapy. The aim of the present study was to evaluate the utility of multiparametric autoantibody analysis performed by a new fully automated particle-based multi-analyte technology (PMAT) digital system in a large multicenter cohort of CTD patients and controls. METHODS: Serum samples from 787 patients with CTD (166 systemic lupus erythematosus; 133 systemic sclerosis; 279 Sjögren's syndrome; 106 idiopathic inflammatory myopathies; 103 undifferentiated CTD), 339 patients with other disorders (disease controls) (118 infectious diseases, 110 organ-specific autoimmune diseases, 111 other rheumatic diseases), and 121 healthy subjects were collected in 13 rheumatologic centers of the FIRMA group. Sera were analyzed with the Aptiva-PMAT instrument (Inova Diagnostics) for a panel of 29 autoantibodies. RESULTS: Multiparametric logistic regression showed that enlarged antibody profiles have a higher diagnostic efficiency than that of individual antibodies or of antibodies that constitute classification criteria for a given disease and that probability of disease increases with multiple positive autoantibodies. CONCLUSIONS: This is the first study that analyzes the clinical and diagnostic impact of autoantibody profiling in CTD. The results obtained with the new Aptiva-PMAT method may open interesting perspectives in the diagnosis and sub-classification of patients with autoimmune rheumatic diseases.

The effect of vitamin D3 and thyroid hormones on the capillaroscopy-confirmed microangiopathy in pediatric patients with a suspicion of systemic connective tissue disease-a single-center experience with Raynaud phenomenon.

Raynaud phenomenon (RP) may be the first manifestation of a systemic connective tissue disease (SCTD). Early detection of dysfunction of small vessels called microangiopathy is essential for the diagnostic process. The focus of this single-center, retrospective study was to investigate the potential dependencies between microvascular image and laboratory markers measured in children with RP. The study analyzed the nail-fold video-capillaroscopy (NVC) findings and laboratory results of 81 children between the ages 6 and 17 who were referred to pediatric rheumatologist with a suspicion of SCTD. Out of 52 patients presenting with RP at the time of evaluation, abnormalities in capillary microscopic imaging were found in 34. NVC findings were then compared to levels of specific biomarkers in serum. Vitamin D3 serum levels have been significantly decreased in patients with RP (23.4 ng/mL ± 8.76 vs. 30.0 ng/mL ± 12.66, P = 0.0148). There were positive significant correlations between levels of vitamin D3 and acute-phase reactants in serum, such as C-reactive protein (P = 0.0292). Furthermore, free thyroxine levels (fT4) in patients with both RP (P = 0.0126) and micro-angiopathy (P = 0.05496) persisted in the lower range of the normal limit (< 1.0 ng/dL). Regular oral supplementation of vitamin D3 should be always considered in children with RP if deficiency is found. Additionally, low fT4 level (< 1.0 ng/dL) should be considered as an indication to perform NVC in patients suspected of SCTD even when they do not present RP.

Treatment of acquired reactive perforating dermatosis - a systematic review.

Reactive perforating dermatosis is a rare chronic skin disease defined by the transepidermal elimination of collagen and/or elastin. In the acquired form in adults, it is frequently associated with diseases such as diabetes and chronic renal failure. No systematic reviews of treatment options are available for this disease. The aim of this systematic review is to summarize all reported treatment options for acquired reactive perforating dermatosis (ARPD). This is a systematic review based on a MEDLINE search of articles in English and German from 1990 to 2016. Most medical literature on the treatment of ARPD is limited to individual case reports and small series of patients. Various therapies that have been tried include antihistamines, topical keratolytics, corticosteroids, tretinoin, oral drugs such as allopurinol or antibiotics, and phototherapy or photochemotherapy. While there are no specific criteria for the evidence-based selection of treatment options for ARPD, the first priority in management of these conditions should be treatment of an underlying disease if present. None of the described modalities has been approved for first-line therapy. It is recommended to choose a combination of drugs that reduce itching and assist in the resolution of the skin lesions at the same time.

Interstitial lung disease in the connective tissue diseases; a paradigm shift in diagnosis and treatment.

Interstitial lung disease (ILD) in the connective tissue diseases (CTD) is amongst the most challenging aspect of care of patients with rheumatic diseases and is the source of significant morbidity and mortality. While there has been progress in our understanding of the natural history of these complications, we still suffer from a limited reservoir of data to confidently determine which patients are at highest risk for disease and those who are at highest risk for disease progression. Treatment options until recently have been limited to anti-inflammatory therapies but with the emerging availability of anti-fibrotic therapies, a shift in strategy is emerging to target therapies based on the specific radiographic, histopathologic features and biomarker profiles that are unique to patients with rheumatic diseases and ILD.

The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies.

RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. OBJECTIVES: To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. METHODS: A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. MEASUREMENTS AND MAIN RESULTS: During the observational period (median 49 months; range, 1-114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. CONCLUSIONS: The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.

Fascial Disorders: Implications for Treatment.

In the past 15 years, multiple articles have appeared that target fascia as an important component of treatment in the field of physical medicine and rehabilitation. To better understand the possible actions of fascial treatments, there is a need to clarify the definition of fascia and how it interacts with various other structures: muscles, nerves, vessels, organs. Fascia is a tissue that occurs throughout the body. However, different kinds of fascia exist. In this narrative review, we demonstrate that symptoms related to dysfunction of the lymphatic system, superficial vein system, and thermoregulation are closely related to dysfunction involving superficial fascia. Dysfunction involving alterations in mechanical coordination, proprioception, balance, myofascial pain, and cramps are more related to deep fascia and the epimysium. Superficial fascia is obviously more superficial than the other types and contains more elastic tissue. Consequently, effective treatment can probably be achieved with light massage or with treatment modalities that use large surfaces that spread the friction in the first layers of the subcutis. The deep fasciae and the epymisium require treatment that generates enough pressure to reach the surface of muscles. For this reason, the use of small surface tools and manual deep friction with the knuckles or elbows are indicated. Due to different anatomical locations and to the qualities of the fascial tissue, it is important to recognize that different modalities of approach have to be taken into consideration when considering treatment options.

Rheumatologic Skin Disease.

In common rheumatologic diseases skin findings are an important diagnostic clue for astute clinicians. Skin manifestations can help identify systemic disease or may require therapy uniquely targeted at the cutaneous problem. This article discusses 3 common rheumatologic conditions seen in adults by dermatologists: cutaneous lupus, dermatomyositis, and morphea. The focus is on the cutaneous findings and clinical presentation. Some approaches to treatment are explored. Clues to help identify systemic disease are also highlighted.

[Magnesium orotate in treatment of chronic hypertension in pregnant women].

We examined 150 pregnant women with essential hypertension (EHT), EHT and connective tissue dysplasia (CTD), and healthy. Presence of CTD aggravated clinical picture of EHT and was associated with pronounced cardialgic, neurological, asthenic, vertebrogenic, visceral, and other syndromes. The use of antihypertensive, metabolic (magnesium orotate) drugs, sedative and uroseptic phytotherapy, application of other nondrug measures in conditions of multidisciplinary dynamic support of the gestational period facilitated regress of clinical symptoms of EHT and EHT+CTD, favorable course of pregnancy and successful delivery.

Lymphedema and lipedema - an overview of conservative treatment.

Lymphedema and lipedema are chronic progressive disorders for which no causal therapy exists so far. Many general practitioners will rarely see these disorders with the consequence that diagnosis is often delayed. The pathophysiological basis is edematization of the tissues. Lymphedema involves an impairment of lymph drainage with resultant fluid build-up. Lipedema arises from an orthostatic predisposition to edema in pathologically increased subcutaneous tissue. Treatment includes complex physical decongestion by manual lymph drainage and absolutely uncompromising compression therapy whether it is by bandage in the intensive phase to reduce edema or with a flat knit compression stocking to maintain volume.

Fenómeno de Raynaud / Raynaud’s Phenomenon

El fenómeno de Raynaud se caracteriza por una disminución de la circulación sanguínea, fundamentalmenteen los dedos de las manos y de los pies, con dolor y cambios de coloración en la piel deuna forma secuencial: blanco, azul y rojo. Es más frecuente en las mujeres, en la 2ª y 3ª décadasde la vida. Se desconoce cuál es su causa, pero guarda relación con el consumo de tabaco, alcohol,y fundamentalmente con los cambios de temperatura y alteraciones emocionales. Se asocia aenfermedades del tejido conectivo, entre las que Esclerodermia y Lupus son las más frecuentes. ElNifedipino es el fármaco de primera elección(AU)

Raynaud’s phenomenon is characterized by a decrease in blood circulation mainly in the fi ngers andtoes, with pain and changes in skin colour which follow a characteristic pattern white, blue and red. Itis more common in women, in the 2nd and 3rd decade of life. The cause is unknown, but is related tosmoking and alcohol consumption, and particularly body temperature changes and emotional stress.It is associated with connective tissue diseases amongst which scleroderma and lupus are the mostfrequent. Nifedipine is the treatment of choice(AU)

Focus on the physical assessment of the infant with Stickler syndrome.

Stickler syndrome is an autosomal dominant, genetic connective tissue disorder characterized by ocular, orofacial, auditory, and skeletal anomalies. The diagnosis of Stickler syndrome is often missed in the newborn period and diagnosed as simply Pierre Robin sequence. For these patients, complications and disabilities could be lessened by further analysis of the family history.Neonatal caregivers are responsible for the immediate care of the newborn with Pierre Robin sequence. The prudent healthcare profession will explore the origin of the condition to provide optimal comprehensive care to the infant and family. This article reviews the physical findings of Stickler syndrome including differentiation between similar syndromes. A systematic review of physical findings is included along with treatment options.

Unusual manifestation of histoplasmosis in connective tissue diseases.

This report describes the coexistence of three patients with rheumatic diseases (systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis) and infections because of Histoplasma capsulatum. Connective tissue diseases and histoplasmosis share several clinical findings. Therefore, histoplasmosis could be misdiagnosed as connective tissue disease or a flare of these diseases. Such cases highlight the importance of awareness of histoplasmosis in immunocompromised patients, particularly in those originating from endemic areas.

Endogenous lipoid pneumonia associated with undifferentiated connective tissue disease (UCTD).

BACKGROUND: Lipoid pneumonia is a rare pulmonary disease, a form of pneumonia that has no classical radiological appearance, thus it can imitate other lung diseases. Lipoid pneumonia is usually classified into two major groups, depending on whether the source of oil/fat in the respiratory tract is from an exogenous or endogenous source. Undifferentiated connective tissue disease is a term used by rheumatologists to define a group of diffuse connective tissue disorders that lack definitive characteristics of any particular well-defined disorder. MATERIAL AND METHODS: A case study is reported of concomitant undifferentiated connective tissue disease and endogenous lipoid pneumonia. RESULTS: Histologically the macrophages appeared filled with lipid and were similar to atherosclerotic foam cell macrophages. Antibiotic and antimycotic treatments were ineffective. However, with concomitant steroid treatment, the patient exhibited absence of lung infiltration as well as other symptoms and was discharged. Therefore it is concluded that the lipoid pneumonia was steroid dependent. CONCLUSION: Since the patient's condition responded to steroid treatment, and it is clear that steroids inhibit phospholipase activity, the authors speculate that the subsequent decreased endoperoxide production may diminish lipid uptake by macrophages via decreasing modification of LDL or other lipid sources.

Early undifferentiated connective tissue disease. V. An inception cohort 5 years later: disease remissions and changes in diagnoses in well established and undifferentiated connective tissue diseases.

OBJECTIVE: To review the diagnoses after 5 years in patients who were identified within 12 months of the onset of well established and undifferentiated connective tissue diseases (CTD); to examine death rates and disease remissions in these patients. METHODS: This inception cohort of 410 patients was identified in 10 academic rheumatology practices. They had less than one year of signs and/or symptoms of CTD. Diagnoses of specific well established CTD were made using accepted diagnostic and classification criteria. The diagnoses after 5 years were determined. RESULTS: Patients with well established CTD tended to remain with the original diagnosis. The progression of unexplained polyarthritis to rheumatoid arthritis occurred infrequently. Ten percent of patients with isolated Raynaud's phenomenon progressed to systemic sclerosis (SSc). The 5 year survival was over 90% in all diagnostic categories, with the exception of SSc, in which it was 64%. CONCLUSION: Patients with a well established CTD usually continued with the same diagnosis. Patients with undifferentiated CTD tended to remain undifferentiated or to remit.

Silicone breast implants and autoimmune disease.

In 1992, the Food and Drug Administration requested a voluntary moratorium on the scale and implantation of silicone-gel-filled breast implants because of growing concern over the lack of scientific and clinical data supporting their safety and effectiveness. Breast implants had been reported to cause serious local complications, and new questions about breast implants and increased risk for autoimmune disease, including the rare but sometimes fatal connective tissue disease scleroderma, were also raised. Since that time, clinical studies have focused on the adjuvant effect of silicone and of potential autoantibody production. Epidemiologic studies have ruled out a large increased risk for connective tissue disease overall in women with breast implants, but samples were too small to rule out an increase in rare connective tissue diseases. Nor were studies properly designed to address whether an atypical syndrome might develop in women with breast implants. Meta-analyses of these studies cannot remedy their underlying methodologic weaknesses. While the question of whether rare connective tissue disease is associated with breast implants may never be answered definitively, recent progress in identifying new syndromes such as fibromyalgia and chronic fatigue syndrome may provide an insight into methodology for evaluating the existence of a silicone-related syndrome in women with breast implants.

Vasospastic disorders. Etiology, recognition, and treatment.

This article discusses a group of disorders commonly unappreciated by physicians. The distinction between Raynaud's disease and Raynaud's phenomenon is reviewed. The classification, pathophysiology, and recognition of the vasospastic diseases is reviewed to lay the foundation for understanding the treatment modalities presented.

Enfermedad humana por adyuvantes: reporte de un caso y revisión de la literatura / Human adyuvant disease: a case report and review of the literature

Se reporta en caso de una paciente de 43 años con diagnóstico de Enfermedad Humana por adyuvantes con manifestaciones que semejaban enfermedad mixta del tejido conectivo. Este caso representa una iatrogenia terapéutica, ya que la inyección de substancia extraña se realizó con fines "curativos". Se incluye una breve revisión.