NOD2 Genes Mutation in a Blau Syndrome Accompany with Congenital Hyperuricemia: A Case Report

Rationale: Blau syndrome (BS) is a chronic auto-inflammatory granulomatous disorder associated with the nucleotide-binding oligomerization domain-containing 2 (NOD2) gene mutations. Gene mutation is one cause of congenital hyperuricemia, However, the relationship between NOD2 and hyperuricemia was unknown. Patient concerns: A 3.5-year-old girl was admitted to hospital because of pain in the left calf and red eyes, otherwise, she suffered from skin rash, and skin cysts in the wrist and ankle joints before.Diagnoses: The girl was diagnosed with sporadic BS (SBS) accompanied with congenital hyperuricemia according to her clinical presentation and gene mutation.Interventions: The patient received prednisolone combined with adalimumab and methotrexate for controlling SBS. Oral febuxostat to alleviate uric acid levels. Outcomes: Her serum uric acid decreased to normal levels after 2 weeks with oral febuxostat tablet. Four months following the treatment, the number of cysts was decreased and ocular damage was not progressed. Lessions: Blau syndrome is a relatively new entity that clinical spectrum continues to expand. This patient provides some information, which would be assist the diagnosis.

Immune Thrombocytopenia: A Rare Presentation of Pulmonary Sarcoidosis

Thrombocytopenia may be the initial presentation of sarcoidosis, which is a systemic granulomatous disorder. Various pathophysiological mechanisms have been identified. Immune thrombocytopenia often has a severe presentation but may respond favourably to immunosuppressive therapy. There are no guidelines for the treatment of thrombocytopenia in sarcoidosis. However, in emergency situations with major bleeding, it seems reasonable to apply the current guidelines recommended for immune thrombocytopenia. The authors report a case of sarcoidosis presenting with severe thrombocytopenia, petechial rash, and nasal and gingival bleeding.

Activation of Downstream mTORC1 Target Ribosomal Protein S6 Kinase (S6K) Can Be Found in a Subgroup of Dutch Patients with Granulomatous Pulmonary Disease

Mechanistic target of rapamycin complex 1 (mTORC1) has been linked to different diseases. The mTORC1 signaling pathway is suggested to play a role in the granuloma formation of sarcoidosis. Recent studies demonstrated conflicting data on mTORC1 activation in patients with sarcoidosis by measuring activation of its downstream target S6 kinase (S6K) with either 33% or 100% of patients. Therefore, the aim of our study was to reevaluate the percentage of S6K activation in sarcoidosis patients in a Dutch cohort. To investigate whether this activation is specific for sarcoid granulomas, we also included Dutch patients with other granulomatous diseases of the lung. The activation of the S6K signaling pathway was evaluated by immunohistochemical staining of its downstream effector phospho-S6 in tissue sections. Active S6K signaling was detected in 32 (43%) of the sarcoidosis patients. Twelve (31%) of the patients with another granulomatous disorder also showed activated S6K signaling, demonstrating that the mTORC1 pathway may be activated in a range for different granulomatous diseases (p = 0.628). Activation of S6K can only be found in a subgroup of patients with sarcoidosis, as well as in patients with other granulomatous pulmonary diseases, such as hypersensitivity pneumonitis or vasculitis. No association between different clinical phenotypes and S6K activation can be found in sarcoidosis.

T Lymphocyte Maturation Profile in the EBUS-TBNA Lymph Node Depending on the DLCO Parameter in Patients with Pulmonary Sarcoidosis

Sarcoidosis (SA) is a systemic granulomatous disorder of unknown etiology with lung and mediastinal lymph nodes (LNs) as the main location. T lymphocytes play important role in the formation of granulomas in SA, but still little is known about the role of maturation profile in the development of inflammatory changes. The aim of this study was to determine the CD4+ and CD8+ T cells maturation profile in LNs and in peripheral blood (PB) and its relation to disease severity expressed by diffusing capacity of the lung for carbon monoxide (DLCO). 29 patients with newly pulmonary SA were studied. Flow cytometry was used for cells evaluation in EBUS-TBNA samples. We observed lower median proportion of T lymphocytes, CD4+ T and CD8+ T cells in patients with DLCO< 80% than in patients with normal diffusion (DLCO > 80%). Patients with DLCO < 80% had lower median proportion of effector and higher median proportion of central memory CD4+ and CD8+ T cells than patients with DLCO > 80%. We reported for the first time that LNs CD4+ and CD8+ T cells maturation differs depending on the DLCO value in sarcoidosis. Lymphocytes profiles in LNs may reflect the immune status of patients with SA and can be analysed by flow cytometry of EBUS-TBNA samples.

Clinical characteristics and outcomes of Korean patients with sarcoidosis

Sarcoidosis is a systemic granulomatous disorder of unknown cause involving multiple organs. Its clinical presentation and prognosis vary among races. We identified the clinical characteristics and outcomes of Korean patients with sarcoidosis. Clinical data of 367 Korean patients with biopsy-proven sarcoidosis diagnosed in 2001–2017 were retrospectively analyzed. Treatment responses included improvement, stability, or progression based on changes in pulmonary sarcoidosis on chest images. The mean age was 47.4 years, and 67.3% of patients were women. The median follow-up period was 80 months. The highest prevalence was observed in individuals aged 50–59 years (30–39 years in men, 50–59 years in women), and the number of diagnoses showed an increasing trend. Lung involvement was the most common (93.5%), followed by the skin, eyes, and extrathoracic lymph nodes. Among patients with lung involvement and a follow-up period of ≥ 3 months, 66.8%, 31.0%, and 2.2% showed improvement, stability, and progression, respectively. Eleven patients (2.9%) died, and the 5-year survival rate was 99%. The number of diagnosed cases showed an increasing trend, and the mean age at diagnosis was increased compared with that in previous reports. Organ involvement was similar to that of Westerners, although the prognosis appeared better.

Case of Cutaneous Sarcoidosis with Direct Osseous Involvement

Sarcoidosis is a granulomatous disorder that presents with cutaneous manifestations in one-third of patients, often as an initial symptom prompting interaction with the healthcare system. Here, we report a case of cutaneous sarcoidosis on the forehead with directly underlying erosive osseous disease. The patient was imaged further, uncovering pulmonary involvement. The lesion was treated with topical and intralesional corticosteroids with significant resolution. Though there exist a range of classic eruptions associated with sarcoidosis, skin involvement can present variably and should prompt additional imaging, particularly to assess for osseous and pulmonary involvement. Topical and intralesional corticosteroids can be effective first-line therapy for cutaneous sarcoidosis.

The relationship between mucosal microbiota, colitis and systemic inflammation in Chronic Granulomatous Disorder

Background: Chronic granulomatous disorder (CGD) is a primary immunodeficiency which is frequently complicated by an inflammatory colitis and is associated with systemic inflammation. Objective: To investigate the role of the microbiome in the pathogenesis of colitis and systemic inflammation. Methods: We performed 16S rDNA sequencing on mucosal biopsy samples from each segment of 10 CGD patients colons, and conducted compositional and functional pathway prediction analyses. Results: The microbiota in samples from colitis patients demonstrated reduced taxonomic alpha diversity compared to unaffected patients, even in apparently normal bowel segments. Functional pathway richness was similar between the colitic and non-colitic mucosa, although metabolic pathways involved in butyrate biosynthesis or utilisation were enriched in patients with colitis and correlated positively with faecal calprotectin levels. One patient with very severe colitis was dominated by Enterococcus spp., while among other patients Bacteroides spp. abundance correlated with colitis severity measured by faecal calprotectin and an endoscopic severity score. In contrast, Blautia abundance associated with low severity scores and mucosal health. Several taxa and functional pathways correlated with concentrations of inflammatory cytokines in blood but not with colitis severity. Notably, dividing patients into High and Low systemic inflammation groups demonstrated clearer separation than on the basis of colitis status in beta diversity analyses. Conclusion: The microbiome is abnormal in CGD-associated colitis and altered functional characteristics probably contribute to pathogenesis. Furthermore, the relationship between the mucosal microbiome and systemic inflammation, independent of colitis status, implies that the microbiome in CGD can influence the inflammatory phenotype of the condition.

Clinicopathological correlation in the diagnosis of granulomatous cutaneous disorders: a retrospective study

<p class="abstract"><strong>Background:</strong> To ascertain the various cutaneous granulomatous disorders and clinicopathological concordance in skin biopsies.</p><p class="abstract"><strong>Methods: </strong>The study included the patients with skin biopsy showing granulomatous infiltrate in a tertiary care center. The cases were categorized according to level of concordance into consistent, corroborative and inconsistent based on the concurrence between clinical and histological diagnosis.</p><p class="abstract"><strong>Results: </strong>Of the total 155 granulomatous disorder, 75.48% showed clinicopathological concordance, 19.35% showed corroborative diagnosis while 5.16% were inconsistent. The maximum number of biopsies performed were in the group of young adult (19-49 years, 57.41%). The most common type of granuloma found was of tuberculoid type and disorders were Hansen’s disease, fungal infection and cutaneous tuberculosis.</p><p class="abstract"><strong>Conclusions:</strong> Our study showed that the coordination of dermatologist and pathologist plays a pivotal role in making accurate diagnosis of granulomatous cutaneous dermatoses.</p>

Acute arthritis, skin rash and Lofgren’s syndrome

Sarcoidosis is an autoimmune multisystem granulomatous disorder of unknown aetiology, which mainly affects the adults in the age group of 20–39 years. The disease can affect any organ in the body but mainly presents as bilateral hilar lymphadenopathy, pulmonary infiltrates, cutaneous lesions, ocular manifestations and arthropathy. Lofgren’s syndrome is an uncommon initial presentation of sarcoidosis which is recognised by the classical triad of acute arthritis, erythema nodosum and bilateral hilar lymphadenopathy. We describe a newly diagnosed case of sarcoidosis who presented as Lofgren’s syndrome. Acute sarcoid arthritis should be kept as one of the differential diagnoses for patients presenting with acute arthritis and skin lesions; and chest X-ray should be considered to rule out bilateral hilar lymphadenopathy in these patients. Early suspicion and identification of classical clinical features are essential to establish early diagnosis.

Childhood sarcoidosis: A case report

Childhood sarcoidosis is a rare multisystemic granulomatous disorder of unknown etiology. The diagnosis is often delayed due to lacking of recognition of clinical features. We report a 23 month-old boy who presented with multiple pinkish papules and painless cystic swellings in his ankles and wrists. A skin biopsy showed multiple sarcoidal granulomatous lesions. He was treated with steroids and had a good response. Childhood sarcoidosis is characterized by arthritis, uveitis, and cutaneous involvement. Glucocorticoids remain the first choice therapy for children with multisystem involvement. The prognosis of early-onset childhood sarcoidosis varies in different studies due to the rarity of the disease.