Atypical Adult-Onset Still's Disease Presenting With Seizures and Myocarditis Complicated by Macrophage Activation Syndrome.

Adult-onset Still's disease (AOSD) is a rare multi-systemic inflammatory disorder characterized by high spiking fevers, nonpruritic, salmon-colored rash, and severe polyarthralgia. Laboratory features typically include elevation in white blood cells, liver enzymes, and ferritin. Central nervous system and cardiac involvements, particularly myocarditis, are rare. Macrophage activation syndrome (MAS) is a well-described complication of AOSD, leading to a high mortality rate. Herein, we describe a case of AOSD complicated by MAS in a 32-year-old male presenting with atypical clinical manifestations, including recurrent seizures, scaly, pruritic, and hyperpigmented rash, and right heart failure due to lymphocytic myocarditis. The patient exhibited a delayed onset of fever, leukocytosis, and transaminitis that initially deterred eligibility for Yamaguchi criteria for AOSD. Bone marrow and lymph node biopsies did not show malignancy, infection, or hemophagocytosis. However, soluble interleukin-2 receptor alpha or soluble CD-25 was elevated. The patient experienced significant improvement on combination therapy of anakinra, methotrexate, and stress-dose steroids. HScore was later indicative of a high probability for MAS. Outpatient management involved prednisone, cyclosporine, and canakinumab for MAS. Seizure and myocarditis are possible presenting features of atypical AOSD. Early recognition of non-criteria AOSD and MAS and prompt initiation of therapy may prevent mortality.

Unraveling the Uncommon: A Case Report of Giant Cell Myocarditis and Examination of Existing Literature.

BACKGROUND Idiopathic giant cell myocarditis (IGCM) is an uncommon and frequently fatal type of myocarditis. It primarily affects young individuals and has the potential to result in heart failure and life-threatening arrhythmias. IGCM seems to be dependent on activation of CD4-positive T lymphocytes and can show improvement with treatment aimed at reducing T-cell function. We present a case of a 65-year-old patient who presented with features of acute heart failure refractory to guideline-directed medical therapy (GDMT), due to IGCM. A review of the natural history and treatment of IGCM is also presented. CASE REPORT A 65-year-old woman with multiple comorbidities was admitted to our hospital for ventricular tachycardia in the setting of progressive non-ischemic heart failure, unresponsive to GDMT. This led to further investigation, including an endomyocardial biopsy, which revealed inflammatory infiltration, with multinucleated giant cells and lymphocytes in the absence of granuloma formation, prompting a diagnosis of IGCM. An implantable cardioverter-defibrillator (ICD) was placed for secondary prevention of sudden cardiac death and the patient was initiated on combined immunosuppressive therapy. Owing to numerous comorbidities, she was determined to be unsuitable for a heart transplant. Unfortunately, she eventually died from complications secondary to the disease. CONCLUSIONS IGCM remains a challenging clinical diagnosis with a poor long-term outcome without heart transplantation. This case highlights the importance of considering atypical causes of heart failure in patients who do not respond to conventional therapies. Early recognition and appropriate management, involving medical and interventional approaches, are crucial in improving outcomes for patients with IGCM.

A 62-Year-Old Immunocompromised Man With Halo Sign on Chest Imaging.

CASE PRESENTATION: A 62-year-old White man with a history of orthotopic liver transplantation 16 years ago for alcoholic liver cirrhosis on chronic immunosuppression and recurrent decompensated cirrhosis of his graft liver complicated by ascites, hepatic encephalopathy, and esophageal varices presented to the hospital with altered mental status. Over the last few weeks, he had reduced frequency of bowel movements and subsequently developed altered sensorium 3 days before presentation. On arrival to the hospital, he was disoriented and had asterixis consistent with hepatic encephalopathy. He was not in respiratory distress, he was saturating well on room air, and his lungs were clear to auscultation bilaterally. Plain chest radiograph showed multiple ill-defined bilateral airspace opacities. A CT scan of the abdomen and pelvis done on admission incidentally showed bilateral pulmonary nodules with surrounding ground-glass halo in the lower lung zones. Given these findings, a dedicated CT scan of his chest was performed that showed numerous bilateral randomly distributed nodular airspace opacities, many with a central solid component and surrounding ground-glass halo. Antifungal therapy was initiated empirically. Serum aspergillus antigen and 1,3 beta D-glucan were negative. He subsequently underwent a bronchoscopy with BAL and transbronchial biopsy. BAL fluid was negative for bacterial, fungal, and acid-fast bacilli cultures. Pathology from the transbronchial biopsy showed atypical epithelioid cells in intravascular spaces.

Aggressive Lymphomas Diagnosed in the Bone Marrow: Two Illustrative Cases.

Lymphomas with subtle patterns in the marrow can be a diagnostic challenge, unless a high index of suspicion is maintained. We present two patients with aggressive lymphomas who presented with cytopenias and the subsequent bone marrow examinations yielded surprising results. These cases highlight the potential usefulness of a bone marrow examination in the diagnosis of lymphomas in the absence of nodal or other tissue specimens.

An Immunohistochemical Survey of SNARE Proteins Shows Distinct Patterns of Expression in Hematolymphoid Neoplasia.

OBJECTIVES: Five proteins from the soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) complex family were studied in normal hematopoietic cells in bone marrow; normal lymphocytes at different stages of maturation and differentiation in bone marrow, thymus, tonsil, and lymph node; malignant lymphomas; and leukemias. METHODS: Sixty-eight reactive and 380 hematopoietic and lymphoid neoplasms were immunohistochemically stained for syntaxin 7 (STX7), vesicle-associated membrane proteins (VAMP2, VAMP7, VAMP8), and synaptosomal-associated protein 23 (SNAP23). RESULTS: STX7 has potential for being a useful marker for distinguishing between normal B precursors (hematogones) vs B lymphoblasts, as well as between the "popcorn" cells of nodular lymphocyte-predominant Hodgkin lymphoma vs the Reed-Sternberg cells of classic Hodgkin lymphoma or the B cells of T-cell, histiocyte-rich B-cell lymphoma. VAMP2 is uniquely expressed by both reactive and malignant plasma cells, in contrast to B-cell non-Hodgkin lymphoma. There is differential expression of SNARE proteins in normal and neoplastic lymphoid tissue depending on lymphocyte maturation stage. CONCLUSIONS: Differential SNARE protein expression in the lymphoid system may have potential use in diagnosis and may offer clues to lymphoma biology. VAMP2 is a promising new plasma cell marker.

Copper deficiency with 20q deletion and a paroxysmal nocturnal haemoglobinuria clone presenting with bicytopenia.

Copper plays an essential role in numerous enzymatic reactions in the human body and hypocupremia manifests itself as cytopenias and/or neuropathy. Copper deficiency is also a mimic of dysplasia, and this may cause diagnostic difficulties with true myelodysplasia. In this case report, we present a patient with anaemia, thrombocytopenia and marginally decreased leucocyte count, who was found to have low copper levels. In addition, he had isolated 20q deletion and a small paroxysmal nocturnal haemoglobinuria clone, which have not been reported previously. His counts normalized after steroid therapy followed by copper supplementation. This case is presented to highlight the fact that copper deficiency may be present without the characteristic morphologic changes, and may be coexisting with other abnormalities.

Thymidine phosphorylase expression in B-cell lymphomas and its significance: a new prognostic marker?

OBJECTIVE: To explore thymidine phosphorylase (TP) expression in B-cell lymphomas (BCLs). TP is expressed by tumor and stromal cells in a variety of cancers. STUDY DESIGN: Paraffin-embedded tissues from follicular lymphomas, diffuse large BCLs (DLBCLs), and benign lymph nodes were studied using immunohistochemical staining with antibodies for TP and CD68. Prognostic markers were used to stain DLBCLs. We correlated TP expression in DLBCL indirectly with prognostic immunomarkers and directly with survival data. RESULTS: TP expression in BCLs was noted in a subset of malignant B cells. TP expression in higher-grade lymphoma was identified in 66% of cases and 11% of lower-grade lymphomas. Macrophages/stromal cells demonstrated an intense cytoplasmic and/or nuclear staining pattern in both lymphoma and benign lymph nodes, confirmed by CD68 coexpression. Increased macrophage/ stromal cells in higher-grade lymphomas are associated with enhanced TP expression in neoplastic B cells (observation only). Sixty-eight percent of TP-positive DLBCLs were of nongerminal center origin, indicating poorer prognosis. CONCLUSION: TP is more likely expressed by malignant B cells in higher-grade lymphomas, and expression of TP possibly results from changes intrinsic to the tumor cells or interactions between microenvironment and tumor. TP positivity in DLBCL correlates with nongerminal center origin and worse outcome.

Astrocyte senescence as a component of Alzheimer's disease.

Aging is the main risk factor for Alzheimer's disease (AD); however, the aspects of the aging process that predispose the brain to the development of AD are largely unknown. Astrocytes perform a myriad of functions in the central nervous system to maintain homeostasis and support neuronal function. In vitro, human astrocytes are highly sensitive to oxidative stress and trigger a senescence program when faced with multiple types of stress. In order to determine whether senescent astrocytes appear in vivo, brain tissue from aged individuals and patients with AD was examined for the presence of senescent astrocytes using p16(INK4a) and matrix metalloproteinase-1 (MMP-1) expression as markers of senescence. Compared with fetal tissue samples (n = 4), a significant increase in p16(INK4a)-positive astrocytes was observed in subjects aged 35 to 50 years (n = 6; P = 0.02) and 78 to 90 years (n = 11; P<10(-6)). In addition, the frontal cortex of AD patients (n = 15) harbored a significantly greater burden of p16(INK4a)-positive astrocytes compared with non-AD adult control subjects of similar ages (n = 25; P = 0.02) and fetal controls (n = 4; P<10(-7)). Consistent with the senescent nature of the p16(INK4a)-positive astrocytes, increased metalloproteinase MMP-1 correlated with p16(INK4a). In vitro, beta-amyloid 1-42 (Aß(1-42)) triggered senescence, driving the expression of p16(INK4a) and senescence-associated beta-galactosidase. In addition, we found that senescent astrocytes produce a number of inflammatory cytokines including interleukin-6 (IL-6), which seems to be regulated by p38MAPK. We propose that an accumulation of p16(INK4a)-positive senescent astrocytes may link increased age and increased risk for sporadic AD.

Expression of thymidine phosphorylase in lymph nodes involved with mycosis fungoides and sézary syndrome.

Thymidine phosphorylase may be overexpressed in both neoplastic cells and tumor stromal cells in a variety of malignancies. Our study explores thymidine phosphorylase expression in lymph nodes (LNs) from patients with mycosis fungoides (MF) or Sézary syndrome (SS). In MF/SS, the LNs may have a pathologic diagnosis of either dermatopathic lymphadenopathy (LN-DL) or involvement by MF/SS (LN-MF). We performed immunohistochemical staining on MF/SS lymph nodes using antibodies to thymidine phosphorylase, CD68, CD21, CD3, and CD4. In both LN-DL and benign nodes, thymidine phosphorylase staining was noted only in macrophages, dendritic cells, and endothelial cells. In LN-MF, thymidine phosphorylase expression was also noted in subsets of intermediate to large neoplastic T cells. Concurrent CD68, CD21, CD3, and CD4 staining supported the above observations. Similar results were noted in the skin and in LN-MF with large cell transformation. Other T-cell lymphomas were also examined (total 7 cases); only enteropathy-type T-cell lymphoma (1 case) showed TP positivity in neoplastic T lymphocytes. We demonstrated that thymidine phosphorylase staining is present in neoplastic T cells in mycosis fungoides. The exact mechanism needs further investigation.

Tumoral calcinosis with vitamin D deficiency.

A 50-year-old woman presented with recurrent calcified mass in the left gluteal region. The clinical, radiological, and biochemical profile confirmed the diagnosis of tumoral calcinosis. She also had associated vitamin D deficiency. The patient underwent surgical removal of the mass to relieve the sciatic nerve compression and was managed with acetazolamide, calcium carbonate, and aluminium hydroxide gel with which she showed significant improvement. The management implications and effect of vitamin D deficiency on phosphate metabolism in the setting of tumoral calcinosis is discussed.

Rhino-orbital-cerebral mucormycosis in type 1 diabetes mellitus.

AIM: To describe the presentation and outcome of rhino-orbital-cerebral mucormycosis (ROCM) in adolescents with type 1 diabetes mellitus (T1DM). METHODS: The medical records of six patients of T1DM with ROCM admitted between October 2001 to January 2004 were analysed. RESULTS: The mean (+/- SD) age and duration of DM of these patients were 16.1+/-3.0 years and 26.3 +/- 24.9 months respectively. Four patients had ROCM at presentation, while two developed it during their hospital stay when recovering from diabetic ketoacidosis. Proptosis (100%) and ptosis (100%) were the most common symptoms, and ophthalmoplegia (85%) and vision loss (85%) were the most common signs. Maxillary sinus (85%) was the commonest paranasal sinus to be involved. All patients received amphotericin B and had appropriate surgery except one. Four patients survived. Patients who had altered sensorium, facial necrosis, palatal perforation and cerebral involvement at presentation had poor outcome. CONCLUSION: High index of suspicion of ROCM in T1DM and combined approach with amphotericin B and appropriate surgery is rewarding.

Microbial Profile of Cumin Seeds and Chili Powder Sold in Retail Shops in the City of Bombay.

A detailed evaluation of the microbial profile of 2 spices, viz. cumin seeds and chili powder, sold in retail shops in the city of Bombay, revealed high aerobic plate counts ranging from 2 × 106/g - 2 × 108/g for chili powder and 1.0 × 104/g to 1.0 × 108/g for cumin. Among the bacteria present, 50-95% constituted sporeformers, which included amylolytic and proteolytic bacilli in both the spices. Aspergillus group was predominant among fungi in chili powder samples. No fungi were found in cumin seed samples examined. Salmonella , Shigella and Vibrio were completely missing from chili and cumin samples. However, Staphylococcus aureus and Bacillus cereus were found in chili powder.