Challenges in diagnosing COVID-19 related disease in pediatric patients with rheumatic disease.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition associated with coronavirus disease 2019. Here we aimed to raise awareness for the symptoms of MIS-C in patients with rheumatic diseases, emphasizing the challenges of the differential features. METHODS: We retrospectively evaluated the demographic and clinical characteristics, laboratory and imaging findings, treatments, and outcomes of six MIS-C patients with previous rheumatic disease. RESULTS: Three of the patients had familial Mediterranean fever (FMF), one had juvenile dermatomyositis, one had systemic juvenile idiopathic arthritis (JIA), and another patient had oligoarticular JIA. All FMF patients presented with fever and abdominal pain, two also had chest pain. The patient with systemic JIA presented with fever, rash, and myalgia. All patients had elevated inflammatory markers and high d-dimer levels. Chest imaging of two FMF patients showed infiltrations compatible with pneumonia. One FMF patient had mildly decreased systolic functions with a shortening fraction of 48% in his echocardiography. Intravenous immunoglobulin and methylprednisolone were administered to all patients. Anakinra was given to four patients. CONCLUSIONS: Clinical and laboratory signs of MIS-C may overlap with the findings of various rheumatic diseases, and this may cause a delay in diagnosis.

Impact of Therapeutic Angiogenesis Using Autologous Bone Marrow-Derived Mononuclear Cells Implantation in Critical Limb Ischemia With Scleroderma　- Subanalysis of the Long-Term Clinical Outcomes Survey.

BACKGROUND: Many patients with collagen disease (CD), particularly scleroderma (SSc), develop critical limb ischemia (CLI), which leads to limb amputation. However, conventional therapies, including revascularization via surgical bypass, showed poor outcomes in CLI patients with CD. Many CLI patients with SSc showed poor responses to combination therapies including intravenous iloprost, PDE-5 inhibitors, and bosentan. Therefore, new methods of improving the peripheral circulation for limb salvage are required. This study was a subanalysis of the long-term clinical outcomes after autologous bone marrow-derived mononuclear cells (BM-MNC) in CLI patients with SSc. Methods and Results: We assessed no-option CLI patients with CD who underwent BM-MNC implantation at 10 institutes; 69 patients (39 with SSc-related diseases (SSc group) and 30 with other CDs (non-SSc group)), were included. The median follow-up duration was 36.5 months. The 10-year overall survival rate was 59.1% in the SSc group and 82.4% in the non-SSc group. The 10-year major amputation-free rates were 97.4% and 82.6%, respectively. The number of major or minor amputations in the SSc group trended to be less than that in the non-SSc group. Significant improvements in visual analog scale scores were observed in both groups. CONCLUSIONS: The BM-MNC implantation may be feasible in no-option CLI patients with CD. In the SSc group, limb salvage rate tended to be higher than in the non-SSc group.

A case of rheumatoid vasculitis with acquired reactive perforating collagenosis.

A 55-year-old man with rheumatoid arthritis (RA) presented hyperkeratotic erythematous papules with crusts or blisters on his limbs and buttocks. A histological study showed acquired reactive perforating collagenosis. Soon, skin lesions changed to umbilicated lesions with black necrosis, and the scar from his skin biopsy ulcerated with induration due to rheumatoid vasculitis. Systemic corticosteroids and tacrolimus administration resolved the RA and skin lesions. Rheumatoid vasculitis with acquired reactive perforating collagenosis has not been reported previously.

Effect of collagen vascular disease-associated interstitial lung disease on the outcomes of lung cancer surgery.

PURPOSE: This study compared the effect of collagen vascular disease-associated interstitial lung disease (CVD-ILD) with that of idiopathic interstitial pneumonias (IIPs) on the outcomes of lung cancer surgery. METHODS: This study retrospectively reviewed the medical records of patients who underwent surgery for non-small cell lung cancer (NSCLC) and compared the data of 16 patients with CVD-ILD with those of 70 patients with IIPs. The patterns of interstitial lung disease (ILD) on chest computed tomography were classified into usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) patterns. RESULTS: The numbers of UIP and NSIP patterns were 10 (62.5%) and 6 (37.5%) patients in CVD-ILD group, and 62 (88.6%) and 8 (11.4%) patients in IIPs group, respectively. A postoperative acute exacerbation (AE) appeared in 1 patient (6.3%) in the CVD-ILD group and 6 patients (8.6%) in the IIPs group. No significant differences in the incidence of postoperative AE and mortalities were observed between the two groups. The five-year overall survival rates of the CVD-ILD and IIPs groups were 37.5 and 49.2%, respectively. CONCLUSIONS: Surgery for NSCLC in CVD-ILD patients appear to cause no increase in postoperative AE and mortality in comparison to that seen in IIPs patients. Similar to IIPs, CVD-ILD might therefore affect the prognosis of resected NSCLC.

Clinical significance of intra-alveolar fibrin deposition in transbronchial lung biopsy in patients with organizing pneumonia.

OBJECTIVE: This study examined the clinical significance of intra-alveolar fibrin deposition (IAFD) in transbronchial lung biopsy specimens obtained from patients with organizing pneumonia. METHODS: Pathological reports of transbronchial lung biopsies performed between 2004 and 2012 were reviewed to identify cases of intra-alveolar organization with or without fibrin deposition. Clinical charts, computed tomography images, and transbronchial lung biopsy specimens from these cases were examined retrospectively. Diagnosis of organizing pneumonia was reevaluated based upon the consensus of a respiratory physician, a radiologist, and a pathologist. RESULTS: Transbronchial lung biopsy results of the reviewed patients with organizing pneumonia found seven patients who had IAFD, and 34 who did not. Seven patients' conditions were associated with collagen vascular disease (CVD), and 34 were cryptogenic. IAFD was significantly associated with high C-reactive protein (CRP) values (>5 mg/dl) (p = 0.0012) and underlying CVD (p = 0.0099). Multivariate analysis revealed that IAFD was independently associated with high CRP values (p = 0.0184). Three of 31 patients and six of 27 patients experienced a relapse of organizing pneumonia within 6 months and 1 year, respectively. IAFD (p = 0.0044) and high CRP values (p = 0.0207) were significantly related to relapse within 6 months, while only CRP was significantly related to relapse within 1 year (p = 0.0007). CONCLUSION: In patients with organizing pneumonia, IAFD was significantly associated with high CRP values. High CRP values and/or IAFD predicted relapse of organizing pneumonia within 6 months to 1 year.

[Preoperative Management of Patients with Collagen Disease and Endocrine Disease].

Collagen disease and endocrine disease are frequently associated with systemic organ dysfunctions with a high perioperative morbidity and mortality. The aims of pre-operative management of these patients are to evaluate the extent of the disease process, systemic consequences and side effects of drugs therapy for the disease and to stabilize the symptoms so that the risk of surgery and anesthesia may be minimized.

Calcinosis Cutis and Calciphylaxis.

Calcinosis cutis (CC) is defined as the deposition of calcium salts in the skin. The condition is divided into 5 types: calciphylaxis and dystrophic, metastatic, idiopathic, and iatrogenic CC. Dystrophic CC is the most common form and usually occurs in association with autoimmune diseases. CC can be treated surgically or with the use of drugs such as diltiazem, bisphosphonates, warfarin, ceftriaxone, probenecid, minocycline, or aluminum hydroxide. Calciphylaxis is defined as calcification of the media of small- and medium-sized blood vessels in the dermis and subcutaneous tissue. Clinically, calciphylaxis causes livedo racemosa, which progresses to retiform purpura and skin necrosis. First-line treatment is with sodium thiosulfate. We present a review of the calcifying disorders of the skin, focusing on their diagnosis and treatment.

Collapsing glomerulopathy in collagen vascular-like disease.

OBJECTIVE: Collapsing glomerulopathy (CG) is a podocytopathy that is usually associated with human immunodeficiency virus (HIV) and parvovirus B19 infections. CG has been reported in association with definite collagen vascular diseases, mainly systemic lupus erythematosus (SLE). There are a few case reports in the nephrology literature of patients with CG and marked serological abnormalities who do not have sufficient clinical findings to diagnose definite collagen vascular disease. We wish to expand the spectrum of rheumatologic disease that accompanies CG. We describe four patients with CG and collagen vascular-like disease and compare these with 14 similar cases reported in the medical literature. METHODS: Case reports of four new patients with CG and collagen vascular-like disease are presented. We performed a systematic literature review to find all other cases and construct a profile of patients with CG and collagen vascular-like disease. RESULTS: All patients had a similar mode of presentation with severe nephrotic range proteinuria and renal insufficiency resistant to steroids and usual immunomodulatory therapy. All patients had positive antinuclear antibodies (ANA) as well as other marked serological abnormalities but few if any clinical findings that would allow for a definitive diagnosis of a specific collagen vascular disease. Almost all patients became dialysis dependent. Mycophenolate mofetil (MMF) may possibly be a therapeutic option. CONCLUSION: Rheumatologists may be asked to consult on patients with severe proteinuria and renal insufficiency in the presence of marked serological abnormalities but few clinical symptoms and should be aware of this podocytopathy.

Orthopedic aspects of collagen disorders.

PURPOSE OF REVIEW: The purpose of this article is to provide the pediatrician with a review of disorders that have the orthopedic manifestation of joint hypermobility. Hypermobility, also termed ligamentous laxity, may present in different parts of the body at different times throughout childhood and adolescence. It may be symptomatic or incidentally found on the physical examination. Many conditions that cause joint hypermobility resolve with nonoperative management, but occasionally operative intervention is required for the best patient outcome. RECENT FINDINGS: In addition, hypermobility may be associated with collagen disorders that affect vital organ systems. Recognition of hypermobility combined with a thorough patient evaluation may be the initial opportunity for the pediatrician to uncover disease that may be managed promptly. SUMMARY: Heightened awareness of subtle hypermobility or symptomatic joint laxity on physical examination facilitates optimal management and favorable outcomes in children with this condition.

Undercover lung damage in pediatrics - a hot spot in morbidity caused by collagenoses.

Connective tissue represents the support matrix and the connection between tissues and organs. In its composition, collagen, the major structural protein, is the main component of the skin, bones, tendons and ligaments. Especially at the pediatric age, its damage in the context of pathologies such as systemic lupus erythematosus, scleroderma or dermatomyositis can have a significant negative impact on the development and optimal functioning of the body. The consequences can extend to various structures (e.g., joints, skin, eyes, lungs, heart, kidneys). Of these, we retain and reveal later in our manuscript, mainly the respiratory involvement. Manifested in various forms that can damage the chest wall, pleura, interstitium or vascularization, lung damage in pediatric systemic inflammatory diseases is underdeveloped in the literature compared to that described in adults. Under the threat of severe evolution, sometimes rapidly progressive and leading to death, it is necessary to increase the popularization of information aimed at physiopathological triggering and maintenance mechanisms, diagnostic means, and therapeutic directions among medical specialists. In addition, we emphasize the need for interdisciplinary collaboration, especially between pediatricians, rheumatologists, infectious disease specialists, pulmonologists, and immunologists. Through our narrative review we aimed to bring up to date, in a concise and easy to assimilate, general principles regarding the pulmonary impact of collagenoses using the most recent articles published in international libraries, duplicated by previous articles, of reference for the targeted pathologies.

A roadmap for fever of unknown origin in children.

Fever of unknown origin (FUO) in adults is conventionally defined by the occurrence of body temperatures above 38.3 degrees C (101 degrees F) for a period of 3 weeks without any identified etiology after a period of 1-week hospitalization. The issue of FUO in pediatrics is rather hazy and still represents a challenging diagnostic dilemma. Most of the available data are limited to nationwide cohorts of patients of any age. The major difficulty in establishing a diagnosis is that the characteristic features rendering specific disorders clinically recognizable are absent or subtle, hence only a painstaking questioning on family background may elicit the correct investigative path. No diagnostic algorithms are actually available and clinicians must rely on a very careful step-by-step evaluation of the single patient. The need for invasive diagnostic techniques should be closely taken into consideration when laboratory tests or simple imaging procedures fail to discern the origin of FUO. Fevers with no reasonable explanation and no localizing signs often conceal different common diseases in children, which tend to display an unusual or atypical pattern. The principal causes behind FUO in pediatric age remain infections, followed by collagen vascular diseases and neoplastic disorders, although most children with malignancies present other systemic signs or suggestive laboratory abnormalities. The possibility of autoinflammatory syndromes, drug fever, and factitious fever should also be taken into account.

Panniculitides, an algorithmic approach.

The issue of inflammatory diseases of subcutis and its mimicries is generally considered a difficult field of dermatopathology. Yet, in my experience, with appropriate biopsies and good clinicopathological correlation, a specific diagnosis of panniculitides can usually be made. Thereby, knowledge about some basic anatomic and pathological issues is essential. Anatomy differentiates within the panniculus between the fatty lobules separated by fibrous septa. Pathologically, inflammation of panniculus is defined and recognized by an inflammatory process which leads to tissue damage and necrosis. Several types of fat necrosis are observed: xanthomatized macrophages in lipophagic necrosis; granular fat necrosis and fat micropseudocysts in liquefactive fat necrosis; mummified adipocytes in "hyalinizing" fat necrosis with/without saponification and/or calcification; and lipomembranous membranes in membranous fat necrosis. In an algorithmic approach the recognition of an inflammatory process recognized by features as elaborated above is best followed in three steps: recognition of pattern, second of subpattern, and finally of presence and composition of inflammatory cells. Pattern differentiates a mostly septal or mostly lobular distribution at scanning magnification. In the subpattern category one looks for the presence or absence of vasculitis, and, if this is the case, the size and the nature of the involved blood vessel: arterioles and small arteries or veins; capillaries or postcapillary venules. The third step will be to identify the nature of the cells present in the inflammatory infiltrate and, finally, to look for additional histopathologic features that allow for a specific final diagnosis in the language of clinical dermatology of disease involving the subcutaneous fat.

Kyrle disease: a case report and literature review.

BACKGROUND: Perforating dermatoses are heterogeneous skin disorders characterized by transepidermal elimination of dermal tissue components. Acquired perforating dermatoses can be divided into four types, according to the eliminated dermal materials: Kyrle disease, perforating reactive collagenosis, elastosis perforans serpiginosa, and perforating folliculitis. They characterize adult patients with coexisting systemic diseases, regardless of the dermal materials eliminated. The association between Kyrle disease and renal failure or diabetes mellitus is common. CASE REPORT: We reported the case of Kyrle disease in a patient with chronic kidney disease. A literature review was performed with the aim to highlight the associated comorbidities and point out the role of early and specific treatment of the cutaneous symptoms and manifestations. CONCLUSIONS: Being Kyrle disease a pruritic condition which adversely affects the patient's quality of life, it would be desirable to place greater therapeutic attention on the alleviation of itching and on the correct management of the underlying comorbidity.

Thoracic manifestations of collagen vascular diseases.

Collagen vascular diseases are a diverse group of immunologically mediated systemic disorders that often lead to thoracic changes. The collagen vascular diseases that most commonly involve the lung are rheumatoid arthritis, progressive systemic sclerosis, systemic lupus erythematosus, polymyositis and dermatomyositis, mixed connective tissue disease, and Sjögren syndrome. Interstitial lung disease and pulmonary arterial hypertension are the main causes of mortality and morbidity among patients with collagen vascular diseases. Given the broad spectrum of possible thoracic manifestations and the varying frequency with which different interstitial lung diseases occur, the interpretation of thoracic images obtained in patients with collagen vascular diseases can be challenging. The task may be more difficult in the presence of treatment-related complications such as drug toxicity and infections, which are common in this group of patients. Although chest radiography is most often used for screening and monitoring of thoracic alterations, high-resolution computed tomography can provide additional information about lung involvement in collagen vascular diseases and may be especially helpful for differentiating specific disease patterns in the lung. General knowledge about the manifestations of thoracic involvement in collagen vascular diseases allows radiologists to provide better guidance for treatment and follow-up of these patients.