Systemic Granulomatous Disease Research Articles

A case of Melkersson-Rosenthal syndrome with temporomandibular joint osteoarthritis: multidisciplinary treatment and autoimmune etiological hypothesis

BackgroundMelkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disorder characterized by recurrent edema, facial palsies, and nerve dysfunctions often associated with the plicata tongue. Although the etiology of MRS is not well understood, there is growing evidence suggesting an autoimmune involvement.Case presentationThis paper presents a case report of a 25-year-old male with MRS as the initial symptom, followed by temporomandibular joint osteoarthritis (TMJ-OA). A comprehensive diagnosis and multidisciplinary treatment approach including surgery, local injections, and oral medication were implemented, resulting in a favorable prognosis.ConclusionsThese findings support the hypothesis that MRS is a systemic granulomatous disease caused by autoimmunity, which may also influence the occurrence and development of TMJ-OA through immune-related mechanisms. This study emphasizes the significance of systemic immune regulation in the treatment of patients with MRS and TMJ-OA comorbid conditions.

Systemic disseminated nocardiosis in a patient with normal immune function: a case report

Nocardiosis, characterized by poor prognosis and high mortality, is a local or systemic suppurative or granulomatous disease caused by Nocardia that is common in immunosuppressed individuals but rare in populations with normal immune function. This paper described one case of Nocardia gipuzkoensis disseminated infection in a patient with normal immune function by outlining the process of treatment, conducting literature review and by outlining the clinical characteristics, diagnostic criteria and standardized treatments of nocardia disease, in the hope of providing reference for subsequent treatment of rare Nocardia subspecies infections.

Cardiac sarcoidosis presenting as multiple right intra-atrial masses mimicking cardiac tumor

BackgroundCardiac sarcoidosis though in itself, a rare entity, very rarely presents primarily with conduction abnormalities as the primary manifestation in the spectrum of presentations accounted by this chronic granulomatous systemic disease. Sarcoidosis presenting as intra-atrial masses is virtually unheard of.CaseA middle aged female presented with progressive conduction system disease was found to have right atrial masses of unclear etiologic on relevant imaging. Over the course of 3 months she underwent a dual-chamber ICD implant for her eventual complete heart block and a surgical resection following an inconclusive biopsy of the right atrial free wall mass. She was then diagnosed with cardiac sarcoidosis and started on immunosupressants almost instantaneously as a part of her treatment.ConclusionThis is an entirely new and unreported presentation of cardiac sarcoidosis as an intra-atrial mass. Through this case we bring light to cardiac sarcoidosis as a potential differential for intra-cardiac masses and how with available data do we go about treating it.

Neurosarcoidosis-Induced Winging Scapula: Efficacy of Infliximab Treatment in Addressing Multifaceted Challenges.

Sarcoidosis, a systemic granulomatous disease primarily affecting the respiratory and lymphatic systems, can rarely manifest as neurosarcoidosis either in isolation or alongside other systemic symptoms. Here, we describe the case of a 45-year-old male with a history of recurrent sinusitis refractory to antibiotics, who presented to the emergency department with sinus congestion and dysphagia. Clinical examination revealed left lower motor neuron facial palsy and enlarged submandibular salivary glands. Despite obtaining negative results from various antibody panels, the patient exhibited elevated Angiotensin Converting Enzyme levels of 83 nmol/kg/min. Additionally, computed tomography chest scans revealed bilateral hilar and mediastinal lymph node enlargement, findings consistent with sarcoidosis. Otorhinolaryngology evaluation for dysphagia confirmed left vocal cord palsy. Following a negative infectious disease workup, submandibular salivary gland biopsy confirmed sarcoidosis. Treatment with mycophenolate mofetil and oral steroids led to gradual improvement in salivary gland swelling, dysphagia, and facial palsy. However, worsening left shoulder pain prompted further investigation, revealing winging of the left scapula on repeat examination. Magnetic resonance imaging (MRI) of the cervical spine revealed a six mm hyperintensity in the left dorsal cord at the C5 level, suggesting possible neurosarcoidosis vs. demyelinating disease. Subsequently, the patient was prescribed anti-tumor necrosis factor alpha inhibitor infliximab. Subsequent MRI of the cervical spine, conducted six months after initiating Infliximab therapy, indicated resolution of the lesions. This positive outcome was supported by the patient's report of symptom improvement, notably reduced shoulder pain and improvement in left scapular winging. This case underscores the unusual co-occurrence of Bell's palsy and vocal cord palsy in the same patient, along with the potential contribution of neurosarcoidosis to the winged scapula. Additionally, it sheds light on the positive response of neurosarcoidosis to Infliximab therapy.

Adalimumab in the Treatment of Complex Sarcoidosis-related Inflammatory Eye Disease: A Case Series

Background: Sarcoidosis is a systemic granulomatous inflammatory disease that is associated with inflammatory eye manifestations such as uveitis, cystoid macular edema, and retinal vasculitis. Although Corticosteroids (CS) have traditionally been the mainstay of treatment, there is a clinical need and growing interest in exploring alternative therapeutic options for patients who are refractory to or intolerant of CS or require long-term steroid-sparing agents. Purpose: This case series aims to describe the effectiveness of adalimumab, an anti-tumor necrosis factor (TNF)-α monoclonal antibody, in the management of complex sarcoidosis-related inflammatory eye disease via reduction in CS dosage and ocular exam findings before and after initiation of adalimumab therapy. Method: A retrospective chart review of patients between 2010 and 2023 seen at our academic center’s rheumatology and eye clinics was conducted, with 5 patients meeting the inclusion criteria. Results: Most patients were able to lower, discontinue, or remain off oral CS, while all 5 patients demonstrated a reduction in uveitis activity, Cystoid Macular Edema (CME), and/or retinal vasculitis. Conclusion: These findings suggest a potential role for adalimumab as an effective and safe therapeutic option in the management of complex sarcoidosis-related inflammatory eye disease.

Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis

BackgroundSarcoidosis is a systemic granulomatous disease of unknown etiology primarily affecting the lungs. Treatment is needed when disease symptoms worsen and organ function deteriorates. In pulmonary sarcoidosis, prednisone and methotrexate (MTX) are the most common anti-inflammatory therapies. However, there is large inter-patient variability in response to treatment, and predictive response markers are currently lacking.ObjectiveIn this study, we investigated the predictive potential of biomarkers in extracellular vesicles (EVs) isolated from biobanked serum of patients with pulmonary sarcoidosis stored prior to start of therapy.MethodsProtein concentrations of a four-protein test panel of inflammatory proteins were measured in a discovery (n = 16) and replication (n = 129) cohort of patients with sarcoidosis and 47 healthy controls. Response to therapy was defined as an improvement of the absolute score of > 5% forced vital capacity (FVC) and/or > 10% diffusion lung of carbon monoxide (DLCO) after 24 weeks compared to baseline (before treatment).ResultsSerum protein levels differed between EV fractions and serum, and between sarcoidosis cases and controls. Serpin C1 concentrations in the low density lipid particle EV fraction were lower at baseline in the group of patients with a good response to MTX treatment in both the discovery cohort (p = 0.059) and in the replication cohort (p = 0.032). EV Serpin C1 showed to be a significant predictor for response to treatment with MTX (OR 0.4; p = 0.032).ConclusionThis study shows that proteins isolated from EVs harbor a distinct signal and have potential as new predictive therapy response biomarkers in sarcoidosis.

Necrotising sarcoid granulomatosis: A report case

Sarcoidosis is a systemic granulomatous disease characterised by the appearance of noncaseifying epithelioid granulomas in the affected organs, most commonly the lungs, skin, and eyes. Necrotizing sarcoid granulomatosis is challenging to diagnose due to its rarity and similarity with other necrotizing disorders. We describe a case of a 47-year male with fever, chest pain, and nodular pulmonary opacities on chest radiograph. Histological examination of the lung tissue confirmed NSG. Diagnostically, infectious causes, vasculitis, and malignancy were excluded. A corticosteroid treatment has been started with a tendency to regression. The key to diagnosis, emphasized in our paper, is the histopathological finding. The course of NSG is similar to sarcoidosis. The treatment of choice is Corticosteroids, but the disease exhibits a tendency towards spontaneous regression.

A Rare Case of Multicentric Reticulohistiocytosis in An Elderly Male Patient

Multicentric reticulohistiocytosis (MRH) is a rare systemic proliferative granulomatous disease of non-Langerhans cells. The aim of this study is to report a case of multicentric reticulohistiocytosis that is easily misdiagnosed in clinical practice. A 74-year-old man sought the Rheumatology office in December 2022 with a main complaint of arthralgia for six months, associated with morning stiffness, joint swelling, and upper and lower limb weakness. On physical examination, papules on the dorsal surface of the proximal interphalangeal joints, base of the nose, and lateral surface of the right hallux were observed. Hyperemia was also identified on the back, and edema of the proximal and distal interphalangeal joints, wrists and knees. Laboratory tests revealed ESR and ANA within normal limits. Tests were negative for Anti-Sm, Anti-RO, rheumatoid factor, Anti-CCP, HIV, and HCV. Chest CT-scan showed right axillary lymph node enlargement, measuring 2.7 cm, atheromatous aorta, and streaks with scattered atelectasis in the lower lobe, without other changes. On total abdominal ultrasound, prostate enlargement was detected. Immunohistochemistry of skin biopsy identified atypical acinar proliferation. Histopathology skin biopsy stained with hematoxylin-eosin (January 2023) showed a dense histiocytic infiltrate. Detail of the histiocytic component displayed “ground glass” eosinophilic cytoplasm. Immunohistochemistry was negative for S100 and CD34 and positive for CD68. Final diagnosis was MRH. The patient underwent treatment with drugs. In conclusion, clinical manifestations, including skin and joint changes, with signs and symptoms of rheumatic disorders (e.g. dermatomyositis and rheumatoid arthritis) similar to those of MRH are expected in rheumatology practice. However, knowledge about disease progression in MRH is limited. Therefore, this case report is described due to its rarity Keywords: Non-Langerhans-Cell Histiocytosis, Pathology, Muticentric Reticulohistiocytosis, Rheumatological Diseases,

Late Presentation of Early-onset Sarcoidosis: A Case Report

Background: Early-onset sarcoidosis is a rare systemic inflammatory granulomatous disease, distinguished by onset before the age of 4 and notably lacking pulmonary involvement. Unfortunately, the condition often shows clinical features similar to juvenile idiopathic arthritis, resulting in the misdiagnosis of numerous patients. This case report delves into the challenges associated with the delayed diagnosis of early-onset sarcoidosis, with a particular focus on the diagnostic methods employed to address this delayed recognition. Case presentation: A 15-year-old girl presented with a history of recurrent fever since infancy, accompanied by rash, arthritis, and joint deformity. Previously misdiagnosed with juvenile idiopathic arthritis, she underwent management with steroids and methotrexate, yielding no improvement. The diagnosis of early-onset sarcoidosis was made during adolescence based on serial examinations, comprehensive laboratory and radiological evaluations, and subsequent histopathology findings. Presently, the patient is receiving treatment with low-dose steroids and biologic therapy (Tocilizumab) and experiencing no disease progression. Conclusion: This case report underscores the importance of considering early-onset sarcoidosis in the differential diagnosis of pediatric patients exhibiting persistent arthritis from an early age. Early detection and treatment are crucial in averting complications and enhancing the overall quality of life.

O03 Sarcoidosis in a Boy with Severe Eczema on Dupilumab

Abstract Sarcoidosis, a systemic granulomatous disease of unknown aetiology, is rare in children. Presentation varies according to the extent and severity of organ involvement and is typically multisystem in older children. Drug induced sarcoidosis-like reaction (DISR) has recently been reported in patients taking Dupilumab. We describe a patient who developed sarcoidosis while on Dupilumab and question whether this was caused by the drug. A 14-year-old boy with severe eczema developed widespread cutaneous nodules and papules after 30 months on Dupilumab. Histology showed non-caseating granulomas. A raised serum angiotensin converting enzyme level, asymptomatic coarse interstitial markings on chest x-ray and small lung nodules on CT scan were also consistent with sarcoidosis. Dupilumab was stopped and hydroxychloroquine and methotrexate commenced. Joint and liver involvement developed 4 months later so systemic glucocorticoids were and the methotrexate was changed to mycophenolate mofetil. To our knowledge there have been 3 previous reports of DISR on Dupilumab. The clinical picture is almost indistinguishable from sarcoidosis. In this case continuing evolution of sarcoidosis 4 months after stopping Dupilumab argues against DISR. However, as Dupilumab becomes more widely used, it is important to be alert to the possibility of new adverse reactions.

Case report: Systemic granulomatous disease with vasculitis in a bull due to hairy vetch (Vicia villosa) toxicosis

A 5-year-old Angus bull presented for generalized alopecia, thickened pleated skin and profuse malodorous watery diarrhea. This bull, along with 6 other beef bulls, had been grazing in a pasture containing hairy vetch (Vicia villosa) for 5-6 months. Diagnostic samples included blood for CBC and chemistry, skin biopsy and scrapings, fecal sample and liver biopsy. Biopsy of skin revealed a chronic, moderate, perivascular and perifollicular, eosinophilic to histiocytic-lymphocytic dermatitis with moderate acanthosis and hyperkeratosis indicative of an ongoing hypersensitivity reaction. The bull did not respond to treatment and was euthanized due to poor prognosis. At necropsy, disseminated systemic granulomatous disease with variable numbers of multinucleated giant cells and eosinophils was observed in multiple organs indicative of systemic granulomatous disease, along with vasculitis in the kidney, liver, and adrenal gland, indicative that vasculitis is involved in the pathogenesis of the lesions. Viral diseases were ruled out by immunohistochemistry of sections of kidney and by in situ hybridization on kidney sections. CD3, CD20, and CD79a lymphocyte markers immunostaining of sections of kidney revealed predominance of CD3 positive lymphocytes, indicative of predominance of T-cell lymphocytes supporting a type-IV hypersensitivity. The vasculitis observed prompted formulating a list of differential diagnoses for infectious diseases that have evidence of vasculitis, including bovine virus diarrhea virus and malignant catarrhal fever. Vasculitis, although previously described in cases of hairy vetch poisoning, is not observed in every single case of the disease. The remaining bulls were not removed from the pasture and none developed clinical signs.

Nerve Growth Factor and Autoimmune Diseases.

NGF plays a crucial immunomodulatory role and increased levels are found in numerous tissues during autoimmune states. NGF directly modulates innate and adaptive immune responses of B and T cells and causes the release of neuropeptides and neurotransmitters controlling the immune system activation in inflamed tissues. Evidence suggests that NGF is involved in the pathogenesis of numerous immune diseases including autoimmune thyroiditis, chronic arthritis, multiple sclerosis, systemic lupus erythematosus, mastocytosis, and chronic granulomatous disease. Furthermore, as NGF levels have been linked to disease severity, it could be considered an optimal early biomarker to identify therapeutic approach efficacy. In conclusion, by gaining insights into how these molecules function and which cells they interact with, future studies can devise targeted therapies to address various neurological, immunological, and other disorders more effectively. This knowledge may pave the way for innovative treatments based on NGF manipulation aimed at improving the quality of life for individuals affected by diseases involving neurotrophins.

Abstract 13055: Different Impact of Immunosuppressive Therapy on Disease Activity and Cardiac Outcome in Isolated Cardiac Sarcoidosis and Systemic Sarcoidosis

Introduction: Sarcoidosis is a systemic granulomatous disease of unknown cause, and cardiac involvement impacts its prognosis. Isolated cardiac sarcoidosis (iCS) has increasingly been recognized; however, its prognosis and efficacy of immunosuppressive therapy remains undetermined. The aim of this study is to clarify the clinical features and outcomes of patients with iCS and systemic sarcoidosis including cardiac involvement (sCS) receiving immunosuppressive therapy. Methods and Results: We retrospectively reviewed the clinical data of 42 patients with sCS and 30 with iCS diagnosed at our institution between 2004 and 2022. We compared the characteristics, and the rate of adverse cardiac events including cardiac death, fatal ventricular tachyarrhythmia, and heart failure hospitalization between groups. The median follow-up duration was 1535 [630, 2555] days, without significant difference between groups. There were no significant differences in sex, NYHA class, and left ventricular ejection fraction between groups. Immunosuppressive agents were administered in 86% of sCS and in 73% of iCS. When analyzed only with patients receiving immunosuppressive therapy (sCS, n=36; iCS, n=21), the cardiac event-free survival was significantly lower in iCS patients than sCS patients (37% vs. 79%, p=0.002). Multivariate analysis showed that iCS was an independent determinant for predicting adverse cardiac events. We evaluated the disease activity in 26 sCS and 16 iCS patients by quantitative measures of FDG-PET including cardiac metabolic volume and total lesion glycolysis, representing accurate three-dimensional distribution and intensity of inflammation. Although iCS patients had lower baseline disease activity than sCS patients, immunosuppressive therapy did not attenuate disease activity in iCS patients in contrast to sCS. Conclusions: iCS showed poorer response to immunosuppressive therapy and worse cardiac prognosis than sCS.

Cost-Effectiveness of Acthar Gel versus Standard of Care for the Treatment of Advanced Symptomatic Sarcoidosis.

Sarcoidosis is a multisystem, inflammatory, systemic granulomatous disease with unknown etiology. Despite the current standard of care (SoC), there is an unmet need for the treatment of advanced symptomatic sarcoidosis. This study assessed the cost-effectiveness of Acthar® Gel (repository corticotropin injection) versus SoC in patients with advanced symptomatic sarcoidosis from the United States (US) payer and societal perspectives over 2 and 3 years. A probabilistic cohort-level state-transition approach was used for this cost-effectiveness analysis. Patients were monitored at the end of a 3-month cycle for the attainment of partial or complete response. Patients in the partial, complete, or no-response state were allowed to transition in each of these states at each 3-month cycle. Following the attainment of response, patients could have a durable response or relapse to a no-response state. Patients in a no-response state received treatment and could transition into a response or no-response state based on the probability of treatment success with the respective treatment. Clinical parameters and health utility data were sourced from the Acthar Gel in Participants with Pulmonary Sarcoidosis (PULSAR) trial (NCT03320070) and healthcare utilization, costs, and disutilities were sourced from the published literature. Base case analysis considered a payer perspective over 2 years. From a payer perspective, Acthar Gel versus SoC results in an incremental cost-effectiveness ratio (ICER) of $134,796 per quality-adjusted life-year (QALY) and $39,179 per QALY over 2 and 3 years, respectively. From a societal perspective, Acthar Gel versus SoC results in an ICER of $117,622 per QALY and $21,967 per QALY over 2 and 3 years, respectively. Sensitivity analysis findings were consistent with the base case. The results from this cost-effectiveness analysis indicate that Acthar Gel is a cost-effective, value-based treatment option for advanced symptomatic sarcoidosis compared to the SoC from the US payer and societal perspectives.

Investigation of the Relationship between PTPN22 Polymorphisms and Lung Sarcoidosis: A cross sectional study

Objective: Sarcoidosis is a systemic granulomatous disease with an unknown etiology characterized by noncaseating granuloma formation. It most often affects the lungs. Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a gene that acts as a negative regulator of T-cell activation. Polymorphisms of this gene are associated with multiple human autoimmune diseases. The aim of this study was to assess the relationship between PTPN22 polymorphisms and lung sarcoidosis in a selected population.
 Methods: The study included 64 patients with lung sarcoidosis and 30 healthy controls. Patients were genotyped to determine two single nucleotide polymorphisms (SNPs) using the polymerase chain reaction (PCR) method. Hardy–Weinberg equilibrium (HWE), an important tool for detecting genotyping errors, was tested. Direct counting was used to estimate genotype frequencies. Logistic regression analysis was performed to compare allele and genotype frequencies between the patient and control groups.
 Results: The results of the study showed no correlation between lung sarcoidosis and the tested two SNPs of the PTPN22 gene (rs2488457, rs1310182) (p>0.05). The categorization analysis according to the clinical features, laboratory, and radiographic characteristics showed no correlation between the tested polymorphism of PTPN22 and these characteristics (p>0.05). 
 Conclusion: The present study demonstrated that the studied two SNPs of the PTPN22 gene (rs2488457, rs1310182) were not correlated with lung sarcoidosis, suggesting that it might be different from other classic autoimmune disorders. There is a need for more studies to verify these results concerning lung sarcoidosis in other ethnic origins.

Cutaneous recurrence of long term pulmonary sarcoidosis - literature review and case report

Sarcoidosis is a systemic granulomatous disease, the exact etiology of which is unknown. This paper presents a case of a patient with a long course of pulmonary sarcoidosis with exacerbation of the disease in the form of skin lesions.
 A 50-year-old female patient was admitted to the Department of Tuberculosis and Lung Diseases, Medical University of Lublin, because of cervical lymphadenopathy. Based on the histopathological examination, she was diagnosed with sarcoidosis. The patient reported constant fatigue, throat tightness and difficulty swallowing, as well as decreased exercise tolerance. Computed tomography studies revealed small nodular changes in both lungs and mediastinal lymphadenopathy. The patient was actively monitored. The results of spirometry tests improved spontaneously and remained at a satisfactory level for years. After 15 years of follow-up, the patient reported skin lesions that are constantly progressing. Examination of the cut from the skin lesion confirmed skin sarcoidosis.
 This case report highlights the varied course of sarcoidosis, which, as a multi-system disease, may show various manifestations. In clinical practice, therefore, one should consider the possibility of disease progression and transmission to multiple organs. It is important that the patient is under constant observation and that new lesions undergo differential diagnosis and histopathological examination.

Increased incidence of thyroid disease in patients with sarcoidosis: a systematic review and meta-analysis.

Sarcoidosis is a multiple systemic granulomatous disease, and its main pathological feature is non-caseous necrotic epithelial granuloma. The pathogenesis is not fully understood. The prevalence of thyroid disease is likely higher among individuals with sarcoidosis. However, this association still lacks clinical evidence. To estimate the incidence of thyroid disease in patients with sarcoidosis. A literature search was conducted using PubMed, Web of Science, Embase, and China National Knowledge Infrastructure literature databases. Fixed- or random-effects models were used for analysis according to heterogeneity. The results were subjected to meta-analysis with odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In total, six articles were included in this meta-analysis, which involved 2044 sarcoidosis cases and 5652 controls. The studies found that the incidence of thyroid disease in patients with sarcoidosis was significantly increased compared to the controls (OR 3.28, 95% CI 1.83-5.88). This systematic review is the first to evaluate the incidence of thyroid disease in sarcoidosis patients, which was increased compared with the controls, suggesting that sarcoidosis patients should be screened for thyroid disease.

Calcium, Phosphate, and Vitamin D Status in Patients with Sarcoidosis-Associations with Disease Activity and Symptoms.

Sarcoidosis is a systemic granulomatous disease with a variety of presentations. One of the known symptoms are altered vitamin D metabolism and hypercalcemia. In our study, we aimed to assess associations between disease activity, inflammatory parameters, and vitamin D and calcium status. The secondary aim was to find any dependencies between calcium and vitamin D metabolism and fatigue and quality of life in patients with sarcoidosis. We enrolled 58 patients with sarcoidosis (47 classified as active disease, 11 classified as non-active) and compared them with 25 healthy volunteers. Calcium concentration was significantly higher in the study group than in healthy controls. It correlated with some inflammatory markers but not with vitamin D status. Not calcium nor vitamin D, but phosphate concentration correlated with life quality was assessed with the use of the Sarcoidosis Health Questionnaire. An association between phosphate concentration and fatigue was also noted, but it did not reach statistical significance. Calcium concentration was higher in patients with sarcoidosis, but it was not an indicator of the disease activity, while phosphate concentration was significantly lower in patients with active sarcoidosis.

Imbalance of Lymphocyte Subsets and CD45RA-Expressing Cells in Intrathoracic Lymph Nodes, Alveolar Compartment and Bloodstream of Pulmonary Sarcoidosis Patients.

Sarcoidosis is a systemic granulomatous disease mainly affecting the lungs and hilomediastinal lymph nodes. It is characterized by non-caseating epithelioid cell granulomas in lymph nodes and lungs. Our study aimed to evaluate and compare T, B and NK cell subsets in the alveolar compartment, lymph nodes and the bloodstream simultaneously in the same patients to elucidate the immune responses associated with the development and progression of sarcoidosis. A secondary aim was to evaluate the distribution of CD45RA-expressing cells in the different anatomical compartments. Patients suspected to have sarcoidosis and who underwent bronchoscopy with bronchoalveolar lavage (BAL), lung-draining lymph node (LLN) biopsy by EBUS-TBNA and peripheral blood (PB) sampling were included in the study. They were monitored at the Regional Referral Centre of Siena University Hospital and the Respiratory Diseases Unit of Perugia Hospital. Multicolour flow cytometry analysis through FASCLyric was performed to assess T, B and NK cell subsets. Thirty-two patients (median age (IQR) 57 (52-58) years) were consecutively and prospectively enrolled. Machine learning analysis created a model which selected CD56dim16bright, CD8, Tfc, Th17, Th12, Tfh17, Tfh2, TcemRA, ThemRA, T naïve, Tc naïve, Breg, CD1d+CD5+, Th-reg, Tfh, Th1 and CD4 cells with an accuracy of 0.9500 (kappa 0.8750). Comparative analysis found 18 cell populations that differed significantly between the three anatomical compartments. The bloodstream was enriched in ThemRA (p = 0.0416), Tfh2 (p = 0.0189), Tfh17 (p = 0.0257), Th2 (p = 0.0212), Th17 (p = 0.0177), Th-naïve (p = 0.0368), CD56dimCD16bright (p < 0.0001), CD8 (p = 0.0319), TcemRA (p < 0.0001) and Tfc cells (p = 0.0004) compared with the alveolar compartment, while Th-reg were lower in PB than BAL (p = 0.0329). The alveolar compartment was enriched in Breg (p = 0.0249) and CD1d+CD5+ (p = 0.0013) with respect to LLN samples and PB. Conversely, Tfh (p = 0.0470), Th1 (p = 0.0322), CD4 (p = 0.0486) and Tc-naïve (p = 0.0009) were more abundant in LLN than in BAL and PB. It has been speculated that changes in the relative contents of PB cells could be related to changes in production and to the selective redistribution of PB cells to granulomatous foci. This study further supports the fact that sarcoidosis is multisystemic in nature. However, the low level of immune cells in peripheral blood of patients with sarcoidosis is concerning. A re-expression of CD45RA on CD4+ and CD8+ cells could result in a reduction in peripheral immune activity. Thus, changes in the spectrum of the bloodstream may reflect both pathogenic and compensatory processes.

Vogt-Koyanagi-Harada Disease Diagnosed in a Black-Skinned Woman in Internal Medicine

Introduction: Vogt-Koyanagi-Harada disease, initially described as an uveomeningoencephalitic syndrome, is a systemic granulomatous autoimmune disease that targets melanocyte-rich tissues, such as the eye, inner ear, meninges, skin and hair. It is one of the most prevalent causes of noninfectious uveitis affecting, more frequently, individuals of pigmented skin, such as Asians, Middle Easterners, Hispanics and Native Americans. However, it is very infrequent among persons of African descent. Here, we report on a case in a black-skinned woman in internal medicine. Clinical Observation: A 45-year-old Malian black-skinned woman with no history of ocular trauma or intraocular surgery presented at internal medicine outpatient clinic with 3-months history of achromic skin patches over the face and trunk, bilateral visual disturbance, bilateral hearing loss with tinnitus and headache. Dermatological examination revealed bilateral, symmetrical achromic lesions over the back, buttocks and eyelids, with scalp poliosis; and perioral pityriasis versicolor lesions. She had no alopecia or other dermatological lesions. Ophthalmological examination revealed a profound drop in visual acuity. Oto-rhino-laringologic examination revealed a discreet hearing loss. Ophthalmological investigations revealed bilateral posterior panuveitis on funduscopic examination, bilateral chronic iridocyclitis on slit- lamp examination, and bilateral choroidal thickening on ocular ultrasound. The diagnosis of Vogt-Koyanagi-Harada was retained, based on the diagnostic criteria established by the American Society for the Study of Uveitis (UAS) in 1978. Prednisone at a dose of 1.5 mg per kilogram tapering courses with adjuvant treatment was initiated. The ophthalmologist's prescription consisted of 1% atropine eye drops, 0.25% timoptol eye drops and dexamethasone eye drops which had been discontinued because of systemic cortitherapy; and that of the dermatologist, Hydrocortisone butyrate 0.1% cream, .......