Severe but reversible pulmonary hypertension in scleromyxedema and multiple myeloma: a case report.

BACKGROUND: Scleromyxedema is a progressive, systemic connective tissue disorder characterized by fibro-mucous skin lesions and increased serum monoclonal immunoglobulin levels. Pulmonary involvement occurs in a subset of patients, though the overall prevalence of pulmonary lesions in scleromyxedema is unknown. Since pulmonary hypertension presumably occurs in these patients due to disease progression and development of additional conditions, treatment of the underlying plasma cell dyscrasia and connective tissue disorder may improve pulmonary hypertension symptoms. CASE PRESENTATION: An elderly patient with scleromyxedema developed pulmonary hypertension refractory to vasodilator and diuretic therapy and subsequently multiple myeloma that responded to a combination therapy of bortezomib, cyclophosphamide, and dexamethasone treatment. CONCLUSIONS: Treatment of the underlying disease(s) that contributed to pulmonary hypertension development with anti-neoplastic agents like bortezomib may improve cardiopulmonary symptoms secondary to reducing abnormal blood cell counts and paraprotein levels.

PURTSCHER-LIKE RETINOPATHY ASSOCIATED WITH ADULT-ONSET STILL DISEASE.

PURPOSE: To describe clinical, laboratory, and funduscopic data of a patient presenting with newly diagnosed adult-onset Still disease and Purtscher-like retinopathy. METHODS: Observational case report. PATIENT: A 43-year-old man presented with a 3-week history of daily high-spiking fever, diffuse arthralgia and myalgia, sore throat, and a transient nonpruritic maculopapular rash. Two weeks from the onset of his illness, he developed a gradual decrease in visual acuity in both eyes. Fundoscopic examination showed multiple areas of retinal whitening, discrete superficial retinal hemorrhages, and few characteristic Purtscher flecken in the left eye. RESULTS: The patient was diagnosed with adult-onset Still disease. We used high-dose corticosteroid therapy with complete resolution of adult-onset Still disease, but it was ineffective for recovery of vision. CONCLUSION: Clinicians should be aware of Purtscher-like retinopathy as a severe ophthalmic complication of adult-onset Still disease.

Treatment-Refractory Sternocostoclavicular Hyperostosis.

Sternocostoclavicular hyperostosis (SCCH) is an infrequent chronic inflammatory disorder of the axial skeleton of unknown origin. SCCH goes often unrecognized due to a low level of awareness for the disorder. It typically presents with relapsing and remitting pain in the shoulder, neck, and anterior chest wall area with occasional swelling and tenderness of the sternoclavicular area. The diagnosis is confirmed radiologically by sclerosis and hyperostosis of the sternoclavicular joints. There have been several reports in which intravenous bisphosphonates and tumor necrosis factor-inhibitors have shown reasonable efficacy in the treatment of this disorder. We report a patient with a long history of SCCH in whom pamidronate 60 mg intravenously every 3 months for 3 years failed to reduce symptom severity and improve radiologic findings.

Pulmonary MALT Lymphoma in Patients with Sjögren's Syndrome.

To describe clinical features and outcomes of seven patients with pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma in the setting of underlying primary Sjögren's syndrome from a single center, we reviewed medical records of consecutive patients with pulmonary MALT lymphoma evaluated at our facility from January 1, 1999 to December 31, 2015 for clinical features, laboratory, pathologic and radiographic findings, management, and outcomes. Out of 13 patients with pulmonary MALT lymphoma, 7 (54 %) met the criteria for Sjögren's syndrome. The mean age at lymphoma diagnosis was 66 years; male-female ratio was 1:6. One-third of patients were asymptomatic at the time lymphoma was discovered. When symptomatic, patients reported nonspecific pulmonary complaints such as cough and dyspnea. All patients had positive antinuclear antibody and anti-SSA/Ro antibody. Rheumatoid factor was positive in six cases. A monoclonal gammopathy was present in three patients; the remaining four had polyclonal hypergammaglobulinemia. The radiologic, morphologic, and immunohistochemical features of primary Sjögren's syndrome-associated pulmonary MALT lymphomas did not differ significantly from pulmonary MALT lymphoma cases in general. All treatment modalities used resulted in complete and sustained response. One patient died 11 years after initial diagnosis with no lymphoma but of another cause. The remaining six patients are still alive and disease-free to date. The present series confirms the favorable course of pulmonary MALT lymphoma in Sjögren's patients. The overall imaging and pathologic features are in accordance with pulmonary MALT lymphoma not associated with primary Sjögren's syndrome. Further studies should be carried out in order to better understand pulmonary MALT lymphomagenesis, treatment, and outcomes in Sjögren's patients.

Cryofibrinogen-Associated Glomerulonephritis.

Cryofibrinogen is an under-recognized cryoprotein. Cryofibrinogen is a cryoprecipitate that develops following plasma refrigeration, but does not occur in cold serum. People with cryofibrinogenemia may be asymptomatic, but this cryoprotein can be associated with thromboembolic disease, particularly affecting the skin. Kidney manifestations are relatively uncommon, but are likely underestimated. We describe clinical features and kidney biopsy results in 2 patients with cryofibrinogen-related kidney disease. Both patients presented with proteinuria and hematuria. One had significant cutaneous ulcers and palpable purpura. Kidney biopsy in both cases showed membranoproliferative glomerulonephritis with no immunoglobulin deposition. Weak segmental capillary wall fibrinogen staining was noted in glomeruli. Immunofluorescence studies following pronase digestion failed to reveal masked immunoglobulin deposits. Ultrastructural studies were distinctive and characterized by organized deposits of large-bore with multilayered tubular structures and fine fibrillary structures in a matrix. To confirm the composition of deposits, we extracted the cryoprecipitate from plasma of a patient and performed ultrastructural studies, which showed identical ultrastructural characteristics to those seen on the kidney biopsy. We also performed proteomic analysis of the cryoprecipitate that confirmed the presence of fibrinogen. Subsequent laboratory evaluation was positive for cryofibrinogen in both patients on multiple occasions. Appropriate therapy was instituted in both patients, which included prednisone, immunosuppressive therapy, and avoidance of cold exposure. In summary, we present clinical, kidney biopsy, and laboratory findings and the treatment and follow-up of cryofibrinogen-associated glomerulonephritis. Awareness of this entity will result in accurate diagnoses, appropriate investigation, and treatment.

Early onset acute tubular necrosis following single infusion of zoledronate.

Zoledronate is a highly potent bisphosphonate widely used in the treatment of postmenopausal osteoporosis. We report the first occurrence of toxic acute tubular necrosis (ATN) following treatment with zoledronate in a patient with osteoporosis. A 63-year-old Caucasian female with rheumatoid arthritis on anti-immune agents received a single dose of zoledronic acid (reclast) for worsening osteoporosis. Twelve days later, she developed renal failure with a rise in serum creatinine from a baseline level of 1.1 mg/dL to 5.5 mg/dL. Renal biopsy showed toxic ATN. Zoledronate was discontinued and the patient had subsequent gradual improvement in renal function with final serum creatinine of 1.8 mg/dL at 1 month of follow up. Careful monitoring of serum creatinine and awareness of the potential nephrotoxicity may avert the development of acute renal failure in osteoporosis patients treated with this agent.

Immune Mediated Necrotizing Myopathy: a Cause of Isolated Myopathy of Neck Extensor Muscle.

Immune mediated necrotizing myopathy (IMNM) is a unique form of myositis that is characterized by distinct muscle biopsy features including abundant myofiber necrosis, degeneration, and regeneration with only minimal, if any, inflammation on muscle biopsy. IMNM is clinically similar to idiopathic inflammatory myopathy (IIM); hence, muscle biopsy is essential to diagnose IMNM. Herein we describe a case of neck extensor weakness due to necrotizing myopathy. Isolated weakness of the neck extensor muscles is uncommon in IIM and IMNM. This case describes the diagnostic work-up, treatments utilized, and 2 year follow-up course without involvement of other muscle groups and without progression of neck extensor muscle weakness. Advanced imaging using magnetic resonance imaging (MRI) facilitated the diagnosis by identifying the affected muscles and site for muscle biopsy.

Angioimmunoblastic T-Cell Lymphoma with Polyarthritis Resembling Rheumatoid Arthritis.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma (PTCL). AITL typically presents with lymphadenopathy, fever, rash, hepatosplenomegaly, and rarely polyarthritis. We report the case of a 50-year-old female who presented with lymphadenopathy, rash, and symmetric polyarthritis. She was later diagnosed with AITL and was treated with chemotherapy with resolution of arthritis. AITL should be suspected in paitents presenting with rheumatoid-like arthritis and diffuse lymphadenopathy.

Idiopathic retroperitoneal fibrosis: clinicopathologic features and outcome analysis.

To describe clinical features and outcomes of 26 patients with idiopathic retroperitoneal fibrosis from a single center, we reviewed medical records of consecutive patients with idiopathic retroperitoneal fibrosis evaluated at our facility from January 1, 1998 to December 31, 2013 for clinical features, laboratory and radiographic findings, management, and outcomes. Twenty-six patients met criteria for idiopathic retroperitoneal fibrosis and were included in the study. Median age at diagnosis was 58 years; male-female ratio was 3.3:1.0. Median duration of symptoms was 7 weeks. Abdominal, flank, and/or low back pain were the most common presenting symptoms. Four patients (15 %) had associated autoimmune or fibrosing disorders. Baseline erythrocyte sedimentation rate was elevated in 17 (77 %) of 22 patients tested and C-reactive protein was elevated in 10 (56 %) of 18 patients tested. Hydronephrosis was present in 17 (68 %) patients; 8 (47 %) of 17 had bilateral hydronephrosis. Retroperitoneal mass biopsy was performed in 18 (69 %) patients. Two patients had idiopathic retroperitoneal fibrosis classifiable as IgG4-related disease. Therapy consisted of medications alone in 7 cases, surgical interventions alone in 7 cases, and a combination in 11 cases. One patient achieved remission with no treatment. Most patients treated medically received initial corticosteroids. Methotrexate (1 case), azathioprine (1 case), mycophenolate mofetil (1 case), and tamoxifen (5 cases) were used. No relapses occurred after a median 5-year follow-up. Two (8 %) patients died; five (19 %) developed cancer after diagnosis. In this series, we emphasize the importance of early diagnosis and therapy for overall favorable prognosis of idiopathic retroperitoneal fibrosis.

Role of Endothelin-1 in a Syndrome of Myelofibrosis and Osteosclerosis.

CONTEXT: Primary myelofibrosis is one of the chronic myeloproliferative disorders characterized by bone marrow fibrosis associated with extramedullary hematopoiesis and osteosclerosis. Endothelin-1 (ET1) is a potent vasoconstrictor that is also a key mediator of osteoblastic bone metastases by stimulating osteoblast proliferation and new bone formation. CASE DESCRIPTION: We report laboratory, radiographic, bone densitometry, and bone histology data of a patient presenting with newly diagnosed, biopsy-proven myelofibrosis and osteosclerosis. We were able to demonstrate abundant ET1 signaling in the bones of our patient. CONCLUSIONS: We believe that ET1 is responsible for the osteosclerosis that develops with advanced myelofibrosis and suggest that ET1 signaling may play a role in other osteosclerotic settings as well.

Bone and bone marrow involvement in sarcoidosis.

Bone and bone marrow involvement in sarcoidosis have been infrequently reported. We aimed to describe the clinical features, radiological descriptions, pathological examinations, and outcomes of three patients with osseous sarcoidosis and one patient with bone marrow sarcoidosis seen at our institution. Our case series included fluorodeoxyglucose positron emission tomography descriptions in assessing the whole-body extent of sarcoidosis. In the era of advanced imaging, large bone and axial skeleton sarcoidosis lesions are more common than previously reported.

Antiphospholipid antibodies-associated diffuse alveolar hemorrhage.

OBJECTIVES: To describe the clinical features and outcomes of 17 patients with primary antiphospholipid syndrome (PAPS) or antiphospholipid antibodies (aPL) and diffuse alveolar hemorrhage (DAH). METHODS: We reviewed the medical records of all patients diagnosed with PAPS-associated DAH and aPL-associated DAH between January 1, 1997, and December 31, 2013, for clinical features, laboratory and radiographic findings, management, and outcomes. RESULTS: A total of 17 patients met the criteria for DAH and had aPL and 10 patients met the criteria for PAPS. The mean age at DAH diagnosis was 57.6 years. Secondary causes of DAH were ruled out. Surgical lung biopsy was performed in 6 cases, 5 of whom had bland hemorrhage. Pulmonary capillaritis was present in only 1 case. Four patients (3 with aPLs and 1 with PAPS) achieved complete remission despite receiving no treatment. The majority of patients treated received initial corticosteroids. Additionally, cyclophosphamide (2 cases), rituximab (1 case), plasma exchange (2 cases), methotrexate (1 case), azathioprine (1 case), and hydroxychloroquine (2 cases) were used. In total, 10 patients (59%) achieved complete and sustained remission with a median length of follow-up of 48 months. Four patients (23%) died (2 with PAPS and 2 with aPLs), all from uncontrolled DAH. Three patients (18%) relapsed after achieving complete remission. CONCLUSIONS: DAH is a rare complication of PAPS that can also arise de novo in aPL-positive individuals. Lung pathology shows either bland hemorrhage or capillaritis. Recognition of this unusual but known complication is important, since early diagnosis and therapy could potentially affect outcomes.

Amiodarone-induced lupus-like syndrome.

Amiodarone has been widely used in treating cardiac arrhythmias. Drug-induced lupus due to amiodarone has been rarely reported. Here, we report the rare occurrence of drug-induced lupus in a 37-year-old male shortly after the initiation of amiodarone. After cessation of drug exposure, the patient recovered completely.

Criteria for the diagnosis of fibromyalgia: validation of the modified 2010 preliminary American College of Rheumatology criteria and the development of alternative criteria.

OBJECTIVE: To validate the 2011 modification of the 2010 American College of Rheumatology (ACR) preliminary criteria for the diagnosis of fibromyalgia (2011ModCr) and develop alternative criteria in a sample of patients with diverse pain disorders that are commonly seen in everyday practice by pain specialists, rheumatologists, and psychologists. METHODS: Eight clinicians from geographically varied locations in the US evaluated patients with chronic pain and psychiatric disorders using a standard set of questions that included the 2011ModCr questions, the Symptom Impact Questionnaire (SIQR), a 28-area pain location inventory (PLI), and the Short Form 36. Alternative diagnostic criteria were developed from the same data set using logistic regression and receiver operating curve analysis. RESULTS: Complete data on 321 patients were evaluated; there were 135 patients with fibromyalgia (according to the 1990 ACR criteria) and 186 patients with 16 other common chronic pain problems. Comparing the 2011ModCr with the 1990 ACR criteria provided a sensitivity of 83%, a specificity of 67%, and a correct classification of 74%. Alternative criteria were derived from the 10-item symptom score from the SIQR symptoms and the 28-area PLI. Maximal diagnostic accuracy was obtained with ≥17 pain sites (range 0-28) and an SIQR symptom score of ≥21 (range 0-50). These alternative criteria had a diagnostic sensitivity of 81%, a specificity of 80%, and a correct classification of 80%. CONCLUSION: The 2011ModCr had robust operating characteristics. Alternative criteria based on symptom items from the SIQR and pain locations from the PLI had comparable operating characteristics, with somewhat better specificity and ease of use.

Early onset imatinib mesylate-induced hepatotoxicity in a patient with gastrointestinal stromal tumors.

Imatinib mesylate is used for the treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia and gastrointestinal stromal tumors (GISTs). It has been associated with severe hepatotoxicity, which may lead to liver failure and death. Few cases of imatinib mesylate-induced liver failure have been reported; most of them were observed in patients treated for chronic myeloid leukemia. To date, 2 cases were reported in patients treated for GISTs. Elevation of liver function tests is usually observed during the first 2-3 months after the initiation of therapy. We report a 46-year-old woman with advanced GISTs who developed hepatotoxicity 11 days after the initiation of imatinib therapy. Before therapy with imatinib, her liver function tests were normal. She had no known risk factors for viral or alcoholic liver disease. Imatinib was her only regular medication, and she had not used acetaminophen or over-the-counter medications. Her serologic studies for hepatitis were all negative. One week after imatinib discontinuation, liver function tests improved significantly. The present report confirms the possibility of early onset imatinib mesylate-induced liver failure in patients treated for GISTs. Surveillance of liver function tests should start early after the initiation of treatment and during all the duration of therapy.

A rheumatoid nodule in an unusual location: mediastinal lymph node.

Rheumatoid arthritis (RA) is a multisystem inflammatory disease characterised by destructive synovitis and varied extra-articular involvement. Rheumatoid lung nodules are the most common pulmonary manifestations of RA. Rheumatoid nodules in mediastinal lymph nodes are extremely uncommon. We describe a male patient with long-standing RA and subcutaneous rheumatoid nodules presenting with multiple lung nodules and mediastinal lymphadenopathies. Definite histopathology of a lymph node was consistent with necrobiotic granuloma due to RA. Clinicians should be aware of rheumatoid nodules as a potential cause of mediastinal lymphadenopathies, mainly in advanced rheumatoid arthritis.

Systemic lupus erythematosus associated with erythema multiforme-like lesions.

Erythema multiforme (EM) and systemic lupus erythematosus (SLE) are common diseases. Their coexistence is known as Rowell syndrome (RS), first described in 1963. Only few cases of RS have been described and some of them questioned its existence. We present two cases of SLE in the setting of a newly developed EM-like eruption, which shares many similarities with the so-called Rowell syndrome.

Multiorgan failure related to human monocytic ehrlichiosis.

Human monocytic ehrlichiosis (HME) is a tick-born disease that presents predominantly as a mild to moderate acute illness. Severe life-threatening disease has been reported with a case death rate of approximately 3%, often in immunosuppressed persons. A delay in therapy initiation has been proven to increase the morbidity of the disease. We report a case of an elderly immunocompetent man with severe HME disease and multiorgan failure to emphasise on the severity of this disease in the elderly, as well as the importance of early therapy for overall favourable prognosis.