Collagen Anomalies as Clues for Diagnosis: Part 1.

BACKGROUND: Collagen is the most abundant protein in the body and the main structural component of the skin. OBJECTIVE: To provide a review of the histopathology of collagen alterations and to propose a classification with the most important types of collagen anomalies in dermatopathology. The authors describe some of the main morphological clues of collagen anomalies for specific diagnosis of some cutaneous inflammatory and neoplastic conditions. METHODS: The authors review histopathologic collagen anomalies, concerning both morphology and disposition in some inflammatory and neoplastic cutaneous conditions, and they review previous terminology and proposed a classification of the most important types of collagen anomalies that can be seen in dermatopathological practice. RESULTS: Collagen anomalies in skin can be classified into lamellar fibrosis, sclerosis, and "balls" and "rings" of collagen. Lamellar fibrosis presents as long and thin collagen bundles forming a delicate network, which can be disposed in a parallel pattern, onion-bulb-like pattern, and storiform pattern. Sclerosis is characterized by large, thick, and eosinophilic bundles of collagen, which may present as a homogenous-diffuse pattern or as individual thick bundles of collagen with few or abundant number of fibroblasts between them. Finally, the authors propose the terms "balls" and "rings" of collagen. The term "balls" of collagen stands for thick, homogenous, eosinophilic, globular collagen bundles, with no distinguishable individual composing fibers, which include the floating sign and the free-floating sign. The term "rings" of collagen is characterized by sclerotic collagen arranged in a homogenous rimming pattern around vessels without independent fibers in its composition. CONCLUSIONS: Collagen anomalies may be important clues to establish specific clues for specific diagnoses in dermatopathology.

[Non-specific interstitial pneumonia (NSIP)]. / Nicht spezifische interstitielle Pneumonie.

Non-specific interstitial pneumonia (NSIP) belongs to the group of idiopathic interstitial pneumonias (IIP). However, NSIP can also be found in several other diseases. For example, the NSIP pattern is most commonly found in interstitial lung disease due to connective tissue disease. In this review, the definition and classification, aetiology, pathogenesis and histology, clinical symptoms, serological markers, lung function parameters, radiographic signs, treatment, and prognosis of NSIP are presented. Idiopathic NSIP as a distinct form of NSIP will be discussed separately.

Nonspecific interstitial pneumonia associated with collagen vascular disease: analysis of CT features to distinguish the various types.

OBJECTIVE: The purpose of this study was to analyze the CT findings of interstitial lung diseases that are associated with collagen vascular disease (CVD), with particular attention to nonspecific interstitial pneumonia (NSIP), and to examine whether it is possible to predict the clinical diagnosis of CVDs based on the CT findings alone. METHODS: CT scans of 49 patients with NSIP associated with CVD (15 males, 34 females; mean age, 55+/-10 years; age range, 25-76 years) were included in this retrospective study. All patients underwent a surgical biopsy. The clinical diagnosis comprised rheumatoid arthritis (RA) (n=15), systemic sclerosis (SSc) (n=8), polymyositis and dermatomyositis (PM/DM) (n=18), Sjögren's syndrome (SjS) (n=4), and mixed connective tissue disease (MCTD) (n=4). Each CT was reviewed by two independent observers who made a clinical diagnosis based on the CT findings alone. RESULTS: The observers made a correct diagnosis for 22 (45%) of the 49 patients. A correct diagnosis was made for: RA in 7 (47%) of 15 patients; SSc in 3 (38%) of 8 patients; PM/DM in 11 (61%) of 18 patients; SjS in 1 (25%) of 4 patients. None of the 4 MCTD cases was diagnosed. CONCLUSION: It is difficult to make a correct clinical diagnosis of the various types of CVDs based solely on CT findings. However, it is probable to make a reasonably accurate clinical diagnosis in cases that show the typical CT findings, especially for PM/DM patients.

[Early diagnosis of chronic systemic inflammatory disorders]. / Frühdiagnostik chronisch entzündlicher Systemerkrankungen.

Functionally relevant damage caused by chronic systemic inflammatory disorders of autoimmune and/or unknown origin can be reduced or sometimes avoided by early initiation of treatment. This requires a correct diagnosis which makes treatment as early as possible. Due to the often uncharacteristic symptoms at the onset of disease, early diagnosis in systemic inflammatory disorders represents a diagnostic challenge. This review outlines current standards and limitations in the early diagnosis of rheumatoid arthritis, collagen vascular diseases and primary systemic vasculitides. Recent advances especially in serology and imaging techniques have improved early diagnosis of systemic inflammatory disorders.

[Interstitial lung disease related to systemic connective tissue diseases]. / Sródmiazszowa choroba pluc w przebiegu ukladowych chorób tkanki lacznej.

Interstitial lung disease (ILD) is one of the most frequent and most serious complications of connective tissue diseases such as systemic sclerosis, systemic lupus erythematosus, dermato- and polymyositis, Sjogren's syndrome, or mixed connective tissue disease. Diagnosis of ILD is often delayed in patients with connective tissue diseases because of the systemic character of the primary condition, restricted physical activity of the patient and insufficient awareness of the physycian. The aim of the current review is to present the up-to-date information on ethiopathology, classification, diagnosis and treatment of ILD in patients with connective tissue diseases.

Collagenoses and cutaneous manifestations of hepar diseases.

The authors discuss cutaneous manifestations of some systemic diseases (collagenoses) and their connection with diseases of liver cells.

The liver in collagen diseases: pathologic study of 160 cases with particular reference to hepatic arteritis, primary biliary cirrhosis, autoimmune hepatitis and nodular regenerative hyperplasia of the liver.

AIMS/BACKGROUND: Among patients with collagen diseases, liver enzyme abnormalities are a relatively common phenomenon. To establish the liver pathology in collagen diseases, detailed pathologic studies were performed on the hepatic diseases in many patients, including various kinds of collagen diseases. METHODS: The livers from 160 patients (120 autopsy and 40 liver biopsy patients) were examined pathologically: 73 with systemic lupus erythematosus (SLE), 32 with rheumatoid arthritis (RA), 18 with polymyositis and dermatomyositis (PM and DM), 15 with systemic sclerosis (SSc), 11 with mixed connective tissue disease (MCTD) and 11 with polyarteritis nodosa (PAN). RESULTS: Liver diseases were divided into three groups: hepatic arteritis, liver diseases associated with collagen diseases (primary biliary cirrhosis, PBC; autoimmune hepatitis, AIH; nodular regenerative hyperplasia of the liver, NRH) and other liver diseases. Hepatic arteritis presenting the features of the PAN type of necrotizing arteritis was found in 27 autopsy patients. The incidence of arteritis in autopsy patients was 100% in PAN and 8.3-25% in other collagen diseases. Primary biliary cirrhosis was observed in 9 patients, 7 of whom (3 with SSc, 2 with RA, 1 with PM and DM, and 1 with MCTD) had antimitochondrial antibodies (AMA)-positive PBC, and 2 SLE patients had AMA-negative PBC. Three patients (2 with SLE and 1 with MCTD) were diagnosed clinicopathologically as having AIH. However, 3 patients (1 with SLE, 1 with MCTD and 1 with PM and DM) with clinical, biochemical and serologic data indicating probable AIH were excluded from the group with AIH association because of the liver histology (no characteristic features of AIH) and clinical course. These results indicated that data without histologic assessments of the liver are not adequate for diagnosing AIH in collagen diseases. Nodular regenerative hyperplasia of the liver was observed in 7 patients (5 with SLE, 1 with SSc and 1 with PAN). CONCLUSION: The present study offers data that are useful for the diagnosis and treatment of patients with collagen diseases and liver abnormalities.

[Current concepts on cartilage collagens and their association with disease]. / Conceptos actuales sobre colágenas de cartílago y su asociación con enfermedades.

The main functional role of the collagenous cartilage fibers is to form a stable network to counteract the hydrodynamic pressure generated by the highly hydrodynamic proteoglycan aggregates. The main collagen present in human cartilage is type II, but other proteins such as type IV, VI, IX, X, XI and XIV are also found albeit in small quantities. Several transgenic mice have been developed to study the structural abnormalities as they relate to human disease. Similarly, the study of these structural abnormalities has renewed the interest regarding their pathogenetic role in some hereditary and acquired diseases of cartilage in humans. It is hoped that gene therapy will help correct these abnormalities. We review here these topics.

[New molecular and clinical information about collagens]. / Novedades moleculares y clínicas de las colágenas.

Collagen is one of the most abundant proteins in human tissues. Together with other connective tissue components (non-collagenous glycoproteins, proteoglycans, laminins, thrombospondins, entactin and tenascin), collagen promotes cellular adhesion, activates intracellular signals, and regulates the biological activities of growth factors and other proteins. During the past 20 years at least 19 genetically different collagenous proteins coded by 30 distinct genes have been identified. Here, we review some new aspects of the collagens that form fibrils, sheets, or beaded filaments, and of the so-called multiplexin collagens. Whenever possible, we give insights regarding the association of the structural abnormalities of these proteins as they relate with human disease(s).

Type II collagenopathies: are there additional family members?

The type II collagenopathies represent a group of chondrodysplasias sharing clinical and radiological manifestations which are expressed as a continuous spectrum of phenotypes, ranging from perinatally lethal to very mild conditions. Their common molecular bases are mutations in the type II collagen gene (COL2A1). We describe one case of lethal platyspondylic dysplasia, Torrance type, and a variant of lethal Kniest dysplasia, neither of which has been reported as a type II collagenopathy. Biochemical studies of cartilage collagens and morphological analysis of cartilage sections suggest that abnormalities of type II collagen structure and biosynthesis are the main pathogenetic factors in both cases. Thus, the phenotypic spectrum of type II collagenopathies might be greater than hitherto suspected.

Juvenile systemic hyalinosis--a rare cause of gingival hypertrophy: a case report.

A 5-year-old boy was referred because of gross gingival hypertrophy which caused severe feeding difficulties in addition to obvious aesthetic concern. The patient also suffered from frequent upper respiratory tract infections and diarrhoea. In addition, he had pigmentation on bony prominences of his hands, elbows, knees and ankles, cutaneous nodules behind his ear and granulomatous tissue adjacent to his nose. Excess gingival tissue was removed under general anaesthesia. Histological features suggested a diagnosis of juvenile hyaline fibromatosis, which is considered to represent the same underlying pathological condition as infantile systemic hyalinosis. It is suggested that systemic hyalinosis should be preceded by 'infantile' or 'juvenile' depending on the clinical presentation.

Oral submucous fibrosis: a new concept in surgical management. Report of 100 cases.

Oral submucous fibrosis (OSF) is a collagen disorder commonly seen in the Indian subcontinent. A series of 100 patients is presented. All lesions were biopsied. The condition was staged into four categories. Very early and early cases were treated by local injection of triamicinolone acetonide, while advanced cases were treated by surgical intervention. A new surgical technique of a palatal island flap based on the greater palatine artery in combination with temporalis myotomoy and bilateral coronoidectomy was used in 35 cases. A follow-up ranging from 6 months to 31/2 year showed good results.

[Anatomy and pathology of the rotator cuff]. / Anatomie und Pathologie der Rotatorenmanschette.

In this contribution we stress the fact that not all rotator cuff tendinopathies are degenerative in nature. Moreover, we insist on a clear distinction between intrinsic and extrinsic tendinopathies. In a final note we point out that the impingement syndrome is not always due to a developmental or acquired spur of the anterior part of the acromion.