Cell Granulomatosis Research Articles

A Clinical Case of Generalized Sarcoidosis with a Predominant Lesion of the Spinal Cord

Sarcoidosis, as systemic epithelioid cell granulomatosis, can be accompanied by damage not only to the intrathoracic lymph nodes and lungs, but also to other organs, in particular, the central nervous system and peripheral lymph nodes. In the spectrum of extrathoracic lesions, spinal cord sarcoidosis occurs only in 6-8 % of cases of all brain lesions. The presented clinical example illustrates the lesion of the spinal cord at the level of the thoracic region, although the literature more often describes the lesion of the cervical region. The disease was accompanied by sarcoidosis of the intrathoracic lymph nodes with rapid spontaneous regression and sarcoidosis of the supraclavicular lymph node. The diagnosis was confirmed after a peripheral lymph node biopsy. Spinal cord sarcoidosis in this patient was characterized by rapid regression against the background of parenteral administration of dexamethasone for 14 days, followed by transfer to tablet forms of prednisone. The positive dynamics of spinal cord sarcoidosis refuted the assumption of the presence of a sarcoid reaction in the lymph nodes against the background of a spinal cord tumor. The use of a course of rehabilitation techniques contributed to the recovery of working capacity.

Eosinophilic granuloma of the skull bone: a case report Langenharns cell granulomatosis

Eosinophilic granuloma is a rare benign tumor which is a variety of histiocytosis-X with unknown etiology. Eosinophilic granuloma occurs as single or multiple lesions of bone destruction. The eosinophilic granuloma of the skull can be asymptomatic or presented with pain and swelling. We present a clinical case of 20-years-old female patient who has entered the Neurosurgery clinic of “St. Marina” University Hospital with clinical manifestation of growing and painful tumor formation in the left frontal area for several weeks. MRI scan discovered evidence of a tumor formation on the left frontal side of the skull, suspicious for an eosinophilic granuloma. Under general anesthesia, an operative treatment was performed. Total extirpation of the tumor mass was achieved and cranioplasty with titanium mesh of the bone defect was performed. Posteratively, the patient had a good cosmetic effect, she was mobilized on the first day after the intervention and discharged from the hospital on the 5th day. Surgery-related complications were not observed. In the postoperative period the patient was followed-up by a hematologist. It is important and recommended for clinicians to include eosinophilic granuloma in the differential diganosis of bone lesions in patients because of the possible expansion of the disease if untreated. A follow-up of a year is necessary for possible recurrence.

Glucocorticoids Are Not Associated with Bone Mineral Density in Patients with Polymyalgia Rheumatica, Giant Cell Arteritis and Other Vasculitides-Cross-Sectional Baseline Analysis of the Prospective Rh-GIOP Cohort.

Background: Glucocorticoids (GCs) can cause osteoporosis (OP). Prior observational research on bone density and the effects of GCs in polymyalgia rheumatica (PMR) and vasculitides is scarce and inconclusive. Methods: Rh-GIOP is a prospective cohort study of bone health in patients with inflammatory rheumatic diseases. In this cross-sectional baseline analysis, we focused on patients with PMR and different forms of vasculitides. Multivariable linear regression was used to model the effect of current and cumulative GC intake on the minimum T-score at any site (mTs; at either lumbar spine or hip), with comprehensive adjustment for confounders. In separate models, GCs were modelled both as continuous and categorical predictors. Sensitivity analyses, stratifying by measurement site and disease, were conducted. Results: A total of 198 patients, with a mean age of 67.7 ± 11.4 years and a mean disease duration of 5.3 ± 6.3 years, were included. Most patients suffered from PMR (36%), giant cell arteritis (26%) or granulomatosis with polyangiitis (17%). Women comprised 66.7% of the patients, and 87.4% were currently taking GCs. The mean CRP was 13.2 ± 26.1 mg/L. OP diagnosed by dual energy X-ray absorptiometry (DXA) (T-score ≤ −2.5) was present in 19.7% of the patients. While 88% were taking vitamin D supplements, calcium supplementation (4%) and treatment with anti-resorptive agents (17%) were relatively infrequent. Only 7% had a vitamin D deficit. Neither current (β(continuous model) = −0.01, 97.5% CI –0.02 to 0.01; p(all models) ≥ 0.49) nor cumulative (β(continuous model) = 0.01, 97.5% CI −0.04 to 0.07; p(all models) ≥ 0.35) GC doses were associated with mTs in any model. CRP was not associated with mTs in any model (p(all models) ≥ 0.56), and no interaction between CRP and GC intake was observed (p for interaction(all models) ≥ 0.32). Across all analyses, lower body mass index (p(all models) ≤ 0.01), history of vertebral fractures (p(all models) ≤ 0.02) and proton-pump inhibitor intake (p(all models) ≤ 0.04) were associated with bone loss. Sensitivity analyses with femoral neck and lumbar spine T-scores as dependent variables led to similar results as the analysis that excluded patients with PMR. Conclusions: In this cohort of PMR and vasculitides, we found a similar prevalence of OP by DXA to the overall elderly German population. Vitamin D supplementation was very common, and vitamin D insufficiency was less frequent than expected in Germans. There was no association between current or cumulative GC intake, CRP and impaired bone density. Proton-pump inhibitors seem to be a major, but somewhat neglected, risk factor for OP and should be given more attention. Our findings require confirmation from longitudinal analyses of the Rh-GIOP and other cohorts.

CD8+ T Cells in GCA and GPA: Bystanders or Active Contributors?

Vasculitis refers to inflammation of blood vessels and can cause a variety of serious complications depending on which vessels are affected. Two different forms of vasculitis are Giant Cell Arteritis (GCA) and Granulomatosis with Polyangiitis (GPA). GCA is the most common form of vasculitis in adults affecting the large arteries and can lead to visual impairment and development of aneurysms. GPA affects small- and medium-sized blood vessels predominantly in the lungs and kidneys resulting in organ failure. Both diseases can potentially be fatal. Although the pathogenesis of GCA and GPA are incompletely understood, a prominent role for CD4+ T cells has been implicated in both diseases. More recently, the role of CD8+ T cells has gained renewed interest. CD8+ T cells are important players in the adaptive immune response against intracellular microorganisms. After a general introduction on the different forms of vasculitis and their association with infections and CD8+ T cells, we review the current knowledge on CD8+ T-cell involvement in the immunopathogenesis of GCA and GPA focusing on phenotypic and functional features of circulating and lesional CD8+ T cells. Furthermore, we discuss to which extent aging is associated with CD8+ T-cell phenotype and function in GCA and GPA.

High-resolution CT in smoking-related interstitial lung diseases.

In addition to chronic obstructive pulmonary disease (COPD) and bronchogenic carcinoma, smoking can also cause interstitial lung diseases (ILDs) such as respiratory bronchiolitis (RB), RB with ILD (RB-ILD), desquamative interstitial pneumonia (DIP), Langerhans cell granulomatosis (LCG) and idiopathic pulmonary fibrosis-usual interstitial pneumonia (IPF-UIP). However, smoking seems to have a protective effect against hypersensitivity pneumonitis (HP), sarcoidosis and organising pneumonia (OP). High-resolution computed tomography (HRCT) has a pivotal role in the differential diagnosis. RB is extremely frequent in smokers, and is considered a marker for smoking exposure. It has no clinical relevance in itself since most patients with RB are asymptomatic. It is frequent to observe the association of RB with other smoking-related diseases, such as LCG or pulmonary neoplasms. In RB-ILD, HRCT features are more conspicuous and diffuse than in RB, but there is no definite cut-off between the two entities and any distinction can only be made by integrating imaging and clinical data. RB, RB-ILD and DIP may represent different degrees of the same pathological process, consisting in a bronchiolar and alveolar inflammatory reaction to smoking. Smoking is also a well-known risk factor for pulmonary fibrosis. Multidisciplinary discussion and follow-up can generally solve even the most difficult cases.

Evaluation of the efficacy and safety of methotrexate in progressive sarcoidosis: a retrospective observational study

Sarcoidosis is epithelioid cell granulomatosis of unknown etiology. All the schemes of its treatment are of a recommendatory nature. Methotrexate (MTT) is considered a second-line drug in the treatment of sarcoidosis.Methods. A retrospective observational study of patients with progressive sarcoidosis (n = 104), treated with MTT once a week, was carried out. Clinical, laboratory, functional and radiation parameters were evaluated with an interval of 3 months ≤ 1 year.Results. The use of MTT was accompanied by an improvement in the radiation picture (64.1% by the end of the year), an improvement not only in spirometry parameters, starting from the 3rd month (54.7%), but also in the general condition of the patients (63.8% – at the 6th month). Adverse reactions with drug withdrawal were most often observed (15.4%) during the first 3 months, and subsequently their frequency decreased.Conclusion. According to the results of the study, it was shown that methotrexate can be recommended for further use in progressive sarcoidosis, as well as in patients, who have previously received systemic glucocorticosteroids.

Ocular Manifestations in Rheumatoid Arthritis, Connective Tissue Disease, and Vasculitis: A Systematic Review and Metaanalysis.

Rheumatoid arthritis (RA) and other rheumatic diseases may present with ocular manifestations.The purpose of our work was to determine the prevalence and type of eye involvement in RA and other connective tissue diseases through a metaanalysis and literature review. A systematic review of the literature was performed using Medline, Web of Science, and the Cochrane Library from their inceptions until January 7, 2019. Conjunctivitis, keratoconjunctivitis sicca, xeropthalmia, uveitis, eye hemorrhage, optic neuritis, papilledema, orbital disease, retinal artery/vein occlusion, macular edema, retinitis, chorioretinitis, scleritis, iridocyclitits, choroid hemorrhage, blindness, and amaurosis fugax were searched for prevalence in patients with RA, systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), dermatomyositis, polymyositis, systemic sclerosis, Sjögren syndrome (SS), undifferentiated connective tissue disease, giant cell arteritis, granulomatosis polyangiitis (GPA; formerly Wegener granulomatosis), systemic vasculitis, and sarcoidosis. There were 3394 studies identified and 65 included. The prevalence of eye involvement was 18% in RA, 26% in GPA, 27% in giant cell arteritis, 27% in sarcoidosis, 31% in SLE, and 35% in APS. The most common manifestation was dry eye syndrome ("dry eye"; keratoconjunctivitis sicca) in most diseases analyzed, with an especially high frequency of 89% in SS. Anterior and posterior uveitis were the most common ocular complications in sarcoidosis, occurring in 16% (95% CI 3-28) and 6% (95% CI 3-9) of patients, respectively. Eye involvement is present in approximately one-fifth of patients with RA, and a one-quarter to one-third of patients with connective tissue diseases (other than SS at 89%) and vasculitis.

Clinically isolated aortitis: pitfalls, progress, and possibilities.

Non-infectious aortitis may be caused by several distinct systemic rheumatologic diseases. In some patients, aortitis is identified either pathologically or radiologically in the absence of clinical evidence of a systemic vasculitis. By consensus nomenclature, such cases are referred to as clinically isolated aortitis (CIA). Some systemic disorders may initially present as CIA including giant cell arteritis (GCA), IgG4-related disease, infectious aortitis, and granulomatosis with polyangiitis. CIA most commonly occurs in women of European descent over the age of 50 and, thus, mirrors the gender, age, and geographic distribution of GCA. CIA most often demonstrates a granulomatous/giant cell pattern of inflammation (GPI), and CIA-GPI is pathologically indistinguishable from aortitis due to GCA. In many cases, CIA may be a manifestation of extracranial GCA. CIA is being identified both pathologically in resected aortic tissue and radiologically by computed tomography scanning, magnetic resonance imaging, and fluorodeoxyglucose positron emission tomography. However, there appears to be significant differences between pathologically defined CIA and radiologically defined CIA. Multiple studies have shown that patients with CIA are at increased risk for subsequent aortic events (new aneurysms or dissections) and thus it is recommended to monitor these patients with periodic aortic imaging. While the data is currently limited, there is increasing evidence that at least some patients with CIA may benefit from immunosuppressive therapy.

On the Tip of the Tongue: Tongue Necrosis as the Initial Presentation of Systemic Vasculitis in Adult and Pediatric Patients - Case Reports and a Literature Review

Tongue necrosis is a rare manifestation of large to medium vessel vasculitis. It has rarely been reported in adults and children. We present two cases of tongue necrosis in adult and pediatric patients with pathologically different etiologies related to different subsets of vasculitis and review their clinical course. To our knowledge, this is the first comprehensive review of the literature on the vasculitides which cause tongue necrosis in adults and children which include giant cell arteritis, polyarteritis nodosa and granulomatosis with polyangiitis.

Risk of Diabetes Mellitus among Patients Diagnosed with Giant Cell Arteritis or Granulomatosis with Polyangiitis: Comparison with the General Population.

Patients with organ- or life-threatening vasculitis receive high cumulative glucocorticoid (GC) doses during their disease course. GC have diabetogenic effects, but the risk of diabetes mellitus (DM) related to vasculitis therapy is not well characterized. We assessed the DM risk among patients diagnosed with giant cell arteritis (GCA) or granulomatosis with polyangiitis (GPA), i.e., patients with relatively common forms of systemic vasculitis. We used Danish healthcare registries to identify 1682 patients diagnosed with GCA and 342 patients diagnosed with GPA from 1997 to 2015 and to obtain information regarding medication exposures. Each patient with vasculitis was matched with 9 population controls. Date of new-onset DM was defined as date of first claimed prescription for an antidiabetic drug. We used Cox regression analyses to calculate incidence rate ratios (IRR) for DM as a measure of the DM risk among patients relative to population controls. Logistic regression was used to study the association between prednisolone/prednisone (PRED) dose and DM. Median duration of followup was 6.5 years [interquartile range (IQR) 2.6-10.4] in the GCA cohort and 5.8 years (IQR 1.7-10.6) in the GPA cohort. During the first year after diagnosis of vasculitis, the IRR for DM was 7.0 (95% CI 5.2-9.3) among patients with GCA and 10.4 (95% CI 4.4-24) among patients with GPA. IRR for DM were not significantly increased in either cohort during later followup periods. Within the first year, treatment with high cumulative prednisolone/PRED doses was associated with new-onset DM among the patients with vasculitis. Patients diagnosed with GCA or GPA have a markedly increased risk of new-onset DM during early treatment phases.

THU0511 Macrophage Growth by Polyploidization in Chronic Inflammation

BackgroundHow macrophages grow at sites of chronic inflammation is not well understood. In rheumatoid arthritis and several granulomatous autoimmune diseases, such as sarcoidosis, giant cell arteriitis and granulomatosis with polyangiitis,...

Radiotherapy in langerhans cell histiocytosis - a rare indication in a rare disease

IntroductionLangerhans Cell Histiocytosis (LCH) represents a rare benign disorder, previously designated as “Histiocytosis X”, “Type II Histiocytosis” or “Langerhans Cell Granulomatosis”. Clinical presentation includes osteolysis, ulcerations of skin and soft tissues but also involvement of the CNS is described.Because treatment concepts are not well defined the German Cooperative Group on Radiotherapy for Benign Diseases performed a retrospective analysis.Methods and materialEight closely cooperating centres collected patients’ data of the past 45 years. As study endpoints disease free survival, recurrent disease, death and therapy related side effects were defined.ResultsA total of 80 patients with histologically proven LCH were irradiated within the past 45 years. According to the LCH classification of Greenberger et al. 37 patients had stage Ia, 21 patients stage Ib, 13 patients stage II and 9 patients stage IIIb and the median age was 29 years. The median Follow up was 54 months (range 9–134 months). A total of 39 patients had a surgical intervention and 23 patients a chemotherapy regimen.Radiation treatment was carried out with a median total dose of 15 Gy (range 3–50.4 Gy). The median single fraction was 2 Gy (range 1.8-3 Gy).Overall, 77% patients achieved a complete remission and 12.5% achieved a partial remission. The long-term control rate reached 80%. Within an actuarial overall 5-year survival of 90% no radiogenic side and late effects ≥EORTC/RTOG II° were observed.ConclusionIn the present study a large collective of irradiated patients was analysed. Radiotherapy (RT) is a very effective and safe treatment option and even low RT doses show sufficient local control.

Pulmonale Hypertonie und Langerhanszell-Granulomatose - erfolgreiche langfristige Therapie mit Sildenafil und Iloprost

A 51-year-old woman (Case A) who had suffered from pulmonary Langerhans' cell granulomatosis for four years presented with progressive exertional dyspnea. A 39-year-old man (Case B) with pulmonary Langerhans' cell granulomatosis for eight years presented with right heart failure. In Case A we found fixed airflow obstruction, hypoxemia, pulmonary fibrosis, bronchiectasis, severe precapillary pulmonary hypertension and a reduced right ventricular function, in Case B moderate airflow obstruction, hypoxemia, pulmonary fibrosis, emphysema and severe precapillary pulmonary hypertension. Pulmonary hypertension due to pulmonary Langerhans' cell granulomatosis was assumed in both patients. After treatment with sildenafil, the woman has experienced long-term improvement for 2.5 years so far. An initially planned lung transplantation was therefore postponed. During inhaled iloprost the man also showed hemodynamic and clinical improvement and was stable for several years. Five years later recurrent right heart failure required an increase in iloprost dose; lung transplantation was then performed. Although no approved drug is available for pulmonary hypertension in Langerhans' cell granulomatosis specific targeted therapies can lead to hemodynamic and long-term clinical improvement. Treatment could be helpful for selected patients with pulmonary hypertension in Langerhans' cell granulomatosis.

Pulmonary Hypertension in Pulmonary Langerhans Cell Granulomatosis

Introduction. Pulmonary Langerhans cell granulomatosis is a rare disease with a variable course. In pulmonary Langerhans cell granulomatosis pulmonary hypertension is frequent and has an independent prognostic impact. A vasculopathy which ist not related to ventilatory disturbance and fibrosis has been identified. An arteriopathy and even a venulopathy have been described. Due to this possible venulopathy vasodilators carry a significant risk for pulmonary congestion and edema. No drugs have been approved until now. Case Presentation. One female with PLCG developed severe PH four years after primary diagnosis of pulmonary Langerhans cell granulomatosis. Retrospective analysis of lung biopsies revealed an arterial vasculopathy at the time of primary diagnosis without clinical signs of PH at this time. Sildenafil led to a sustained improvement of hemodynamic features and exercise capacity. Conclusion. This paper underlines that patients with PLCG with an arterial vasculopathy-related PH might improve under sildenafil. Further trials addressing treatment of PH and vasculopathy are needed.

CLINICAL PICTURE OF PULMONARY LANGERHANS CELL GRANULOMATOSIS 2000–2008

PURPOSE: Pulmonary Lungerhans cell granulomatosis is a rare disease with variable clinical findings and uncertain prognosis. The aim of our study was to prospectively evaluate the clinical picture of pulmonary Langerhans cells granulomatosis in patients admitted to our Department in 2000–2008.

Pulmonary veno-occlusive disease

Pulmonary veno-occlusive disease (PVOD) is currently classified as a subgroup of pulmonary arterial hypertension (PAH) and accounts for 5-10% of cases initially considered to be idiopathic PAH. PVOD has been described as idiopathic or complicating other conditions, including connective tissue diseases, HIV infection, bone marrow transplantation, sarcoidosis and pulmonary Langerhans cell granulomatosis. PVOD shares broadly similar clinical presentation, genetic background and haemodynamic characteristics with PAH. Compared to PAH, PVOD is characterised by a higher male/female ratio, higher tobacco exposure, lower arterial oxygen tension at rest, lower diffusing capacity of the lung for carbon monoxide, and lower oxygen saturation nadir during the 6-min walk test. High-resolution computed tomography (HRCT) of the chest can be suggestive of PVOD in the presence of centrilobular ground-glass opacities, septal lines and lymph node enlargement. Similarly, occult alveolar haemorrhage is associated with PVOD. A noninvasive diagnostic approach using HRCT of the chest, arterial blood gases, pulmonary function tests and bronchoalveolar lavage could be helpful for the detection of PVOD patients and in avoiding high-risk surgical lung biopsy for histological confirmation. PVOD is characterised by a poor prognosis and the possibility of developing severe pulmonary oedema with specific PAH therapy. Lung transplantation is the treatment of choice. Cautious use of specific PAH therapy can, however, be helpful in some patients.

Présentation pulmonaire inhabituelle d’une histiocytose à cellules de Langerhans systémique

An 80-year-old nonsmoking man was referred to our hospital with bilateral perihilar pulmonary opacities. He had a history of epilepsy, sclerosing cholangitis, cutaneous lesions previously diagnosed as localised Langerhans cell histiocytosis. Symptoms included dry cough and dyspnea. Chest CT showed bilateral perihilar alveolar consolidation with bronchiectasis. Histological examination of a lung biopsy showed typical features of Langerhans cell granulomatosis. Investigations revealed anterior and posterior hypopituitarism. An important improvement occurred with corticosteroid and vinblastine treatment.

The airways in sarcoidosis

In a retrospective study of 152 patients with histologically proven sarcoidosis (stage I: 76 patients; stage II: 70; stage III: 6) clinical pointers towards respiratory involvement were found in 45%, morphological evidence in the form of epithelioid cell granulomatosis of the mucosa in 20%, and histological findings in the form of nonspecific inflammatory and degenerative mucosal changes in 90%. In 30% of patients there were indications of respiratory tract obstruction in the lung function tests. Circumscribed central granulomatous lesions with stenoses of a segment or lobar bronchus and resulting atelectasis were rare, seen in only three. Generalized central respiratory tract obstruction, diagnosed by an increase in airway resistance, was present in 8-17% and was stage-dependent. It correlated in a statistically significant manner with the occurrence of epithelioid-cell granulomas. Peripheral airway obstruction with involvement of the small airways, of which there was functional evidence, can be caused by peribronchial formation of granulomas, as typically seen in transbronchial lung biopsies. But these findings were not of any clinical significance nor required changes in the therapeutic regimen. Functionally precipitated airway obstruction caused by bronchospasm was not demonstrated in the inhalation carbachol provocation test. On the other hand, a subgroup of sarcoidosis patients with raised serum IgE levels had a significantly lower stimulation threshold of the respiratory tract to carbachol.

Signal Intensity Changes on MRI During the Healing Process of Spinal Langerhans Cell Granulomatosis

Two patients with spinal Langerhans cell granulomatosis were followed by magnetic resonance imaging, and the observed signal changes were detailed. Both patients had no neurologic abnormalities but back pain. They were treated by immobilization with a brace and bed rest. Their back pain disappeared after about a month. At the first visit, the tumorous lesions involving vertebrae showed mainly low signal intensity on T1-weighted imaging (T1WI) and high intensity on T2-weighted imaging (T2WI). They were clearly enhanced by gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Their original intensities changed to iso-intensities on both T1WI and T2WI without enhancement by Gd-DTPA after a year. These signal changes might indicate the healing stage of the involved vertebrae and recommend the removal of the spinal brace.

Pulmonary Langerhans Cell Granulomatosis: Clinical and Laboratory Data in 10 Greek Patients

Pulmonary Langerhans Cell Granulomatosis: Clinical and Laboratory Data in 10 Greek Patients