Musculoskeletal manifestations of primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) can be associated with a variety of musculoskeletal complaints, which occasionally can be the leading or presenting manifestation. In this paper, we describe the musculoskeletal manifestations observed in patients with primary hyperparathyroidism. Medical record reviews of a select population of 74 patients with primary hyperparathyroidism are seen in a rheumatology practice. Bone manifestations included back pain in 11 patients (15.2 %), generalized bone pain in 7 patients (9.7 %), rib cage/chest pain in 6 (8.3 %), pseudoclubbing in 3, and a giant cell tumor of the mandible in 2 (2.3 %) patients. Articular manifestations such as chondrocalcinosis with or without apatite deposition disease were seen in 13 (17.7 %), arthralgias in 11 (15.2 %), and non-specific synovitis in 7 (9.7 %). Muscle weakness was observed in six patients (8.3 %) and myalgias in three (4.6 %). Less common manifestations such as Achilles tendon rupture, Jaccoud-like arthropathy, sacral insufficiency fracture, arthritis associated with fever of unknown origin (FUO), meningitis, cervical cord compression, and persistent headache were observed in single patients. Musculoskeletal findings are still a frequent and important presentation in patients with primary hyperparathyroidism seen in rheumatology practice. Some of these manifestations can be quite unusual and may represent diagnostic dilemmas to the practicing rheumatologist and/or endocrinologist.

Clinical and magnetic resonance imaging manifestations of neurosarcoidosis.

OBJECTIVES: To describe clinical and neuroimaging manifestations of neurosarcoidosis in a cohort of 21 patients. PATIENTS AND METHODS: We reviewed records of 21 patients with sarcoidosis and central nervous system (CNS) manifestations referred to Cooper University Hospital, with emphasis on neuroimaging findings and associated clinical and laboratory evidence of sarcoidosis. Nineteen patients were categorized as having "definite," "probable," or "possible" neurosarcoidosis, while 1 had associated CNS vasculitis and another had Hodgkins lymphoma with cauda equina syndrome. RESULTS: The most common manifestations included myelopathy, cranial neuropathies, and encephalopathy. In 6 patients, CNS biopsy showed sterile, noncaseating granuloma (NCG), while in the remainder, the diagnosis was established through a combination of clinical, radiographic, and laboratory findings. Notably, 10 patients developed acute neurological emergencies, including seizures, spinal cord compression, and increased intracranial pressure. Findings on magnetic resonance imaging (MRI) included a variety of manifestations, including isolated mass lesion, diffuse intraparenchymal inflammatory lesions in the brain and spinal cord, leptomeningeal enhancement, hydrocephalus, and intracranial hemorrhage. CONCLUSIONS: Sarcoidosis is associated with diverse neurological manifestations and neuroimaging findings. The diagnosis of isolated CNS sarcoidosis requires a biopsy to document the presence of sterile NCG and to exclude neoplasms and other granulomatous diseases. When a biopsy of the CNS is not possible, a diagnosis of neurosarcoidosis can reasonably be supported in many patients by MRI findings and exclusion of other disorders. RELEVANCE: Optimum management of patients with neurosarcoidosis relies on the ability of clinicians to recognize the broad spectrum of clinical and neuroimaging manifestations of the disorder.

Mutations in the amino terminus of ANKH in two US families with calcium pyrophosphate dihydrate crystal deposition disease.

OBJECTIVE: To analyze ANKH in families with calcium pyrophosphate dihydrate crystal deposition disease (CPPD) for disease-causing mutations. METHODS: Two US families (one of British ancestry and the other of German/Swiss ancestry) with autosomal-dominant CPPD, whose disease phenotypes were found to be linked to chromosome 5p15.1 (locus symbol CCAL2), were screened by direct sequencing for mutations in ANKH, a gene in the CCAL2 candidate interval that has been shown to harbor mutations in other families with CPPD. Observed sequence variants were confirmed by antisense sequencing, and expression of the mutant allele was verified by reverse transcriptase-polymerase chain reaction amplification of messenger RNA followed by direct sequencing. RESULTS: The two US families displayed the same mutation at position 5 of the ANKH gene product (P5T). All affected members were heterozygous for the P-to-T variant, and the mutation was not seen in 204 control alleles. The two families displayed distinct disease haplotypes, suggesting that they were unrelated to each other. CONCLUSION: These observations represent the fourth and fifth families with heritable CPPD whose disease phenotypes are linked to the CCAL2 locus and who have missense mutations in the amino terminus of ANKH. This same position (P5) was the site of a missense mutation in an Argentine family of northern Italian ancestry; however, the sequence variant in that family generated a P5L mutation. The distinct disease haplotypes among the 3 families with P5 mutations suggest that the mutations arose independently and that the evolutionarily conserved P5 position of ANKH may represent a hot spot for mutation in families with autosomal-dominant CPPD.

Rheumatoid nodulosis: is it a different subset of rheumatoid arthritis?

Rheumatoid nodulosis is an entity that describes a particular variant of polyarthritis associated with early manifestations of palindromic rheumatism, radiologic subchondral bone cysts, and subcutaneous rheumatoid nodules. This study describes the clinical, radiologic, histologic, crystallographic, and laboratory findings, as well as the outcome in a group of 16 patients with rheumatoid nodulosis that were followed for a period of 1-12 years. Six of these patients had an aggressive course and developed classic erosive polyarticular rheumatoid arthritis, while the others continued having episodic arthritis without erosive disease. Seven patients had cholesterol crystals in olecranon bursae containing nodules. Second-line drugs used to control the articular manifestations did not improve the nodulosis, erosive, or cystic subchondral bone changes. Rheumatoid nodulosis mimics several other rheumatic diseases, and in about 40%, classic erosive rheumatoid arthritis develops. The presence of cholesterol crystals in rheumatoid nodules or affected bursae can increase the confusion with other crystal-induced arthritis, in particular, tophaceous monosodium urate gout or xanthomatosis.

Oncogenic hypophosphatemic osteomalacia associated with a nasal hemangiopericytoma.

We report a patient with a nasal hemangiopericytoma associated with an oncogenic hypophosphatemic osteomalacia (OHO). This syndrome results from tumor products that decrease renal tubular phosphate resorption, leading to the osteomalacia. This patient presented with classic bone manifestations of osteomalacia and a nasal tumor. Laboratory studies performed before the first resection of the tumor included normal serum calcium, hypophosphatemia due to decreased tubular reabsorption of phosphate, and an undetectable serum 1,25 dihydroxy vitamin D level. Serum parathormone level was normal. Anterior iliac crest bone biopsy showed characteristic signs of osteomalacia that included increased osteoid and delayed mineralization. A partial resection of the nasal tumor was performed. After the first surgery the patient showed detectable serum level of 1,25 dihydroxy vitamin D, and transient normalization of the tubular reabsorption of phosphate. The patient was also treated with phosphate supplements and vitamin D with transient control of her clinical manifestations and improvement of the radiographic signs of osteomalacia. Three months after surgery, the serum level of 1,25 dihydroxy vitamin D level again became undetectable. After selective embolization of the tumor, followed by an apparent complete tumor resection and postoperative radiation therapy, her hypophosphatemia and decreased phosphate tubular reabsorption persisted. Therefore, biochemical changes associated with hemangiopericytoma induced OHO may persist even after apparent total tumor resection. Clinicians should be aware of the oncogenic basis for some osteomalacia, as seen in this patient.

Musculoskeletal manifestations of osteomalacia and rickets.

Osteomalacia (OM) is still an important metabolic bone disease with increased prevalence in certain regions of the world as well as in the urban population of elderly confined. The disease presents with a wide variety of clinical, biochemical and radiographic manifestations mimicking other musculoskeletal disorders, including 'osteoporosis'. In this chapter, we provide the basis for its clinical diagnosis and management. There have been significant recent advances in the understanding of vitamin D deficiency and hypophosphataemic osteomalacia, which can now assist clinicians in the precise diagnosis and treatment of this disease. In this chapter we also review the various underlying aetiologies. The successful management of OM depends on the underlying aetiology.

Oxalate crystal deposition disease.

In addition to monosodium urate, calcium pyrophosphate dihydrate, and apatite crystals, oxalate crystals are less often found in synovial fluids in association with acute or chronic arthritis. Oxalate crystal deposition disease is seen in patients with primary hyperoxaluria types 1 and 2 (PH1 and 2) and in patients with end-stage renal disease managed with long-term dialysis. Oxalate crystal deposits are found mainly in kidneys, bone, skin, and vessels, and less often inside the joints. Musculoskeletal and systemic manifestations of oxalate crystal deposition disease may be confused with those observed with the other most common types of crystal deposition diseases. Clinical and radiographic features include calcium oxalate osteopathy, acute and chronic arthropathy with chondrocalcinosis, synovial calcification, and miliary skin calcium oxalate deposits and vascular calcifications that affect mainly the hands and feet. Systemic life-threatening cardiovascular, neurologic, and hematologic manifestations are rare. Genomic DNA studies have identified those genetic defects of PH1 and PH2 that allow a precise early diagnosis. Kidney transplantation has poor outcome as a result of graft oxalosis. Combined liver and kidney transplantation is the treatment of choice in patients with PH1 and advanced renal failure. Pre-emptive isolated liver transplantation is the preferred treatment in patients who develop the disease during infancy with progressive manifestations of oxalosis. These novel findings in the understanding of the molecular and enzymatic aspects of primary hyperoxalurias have provided a more rational basis for the management and prevention of oxalate crystal deposition disease. This information may lead to a better understanding and effective management of other common calcium-containing crystal deposition diseases.

A study of musculoskeletal manifestations in 12 patients with SAPHO syndrome.

Synovium and synovial fluid findings in SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome have not been well characterized, and only a few patients have been described in the Americas. We describe clinical, pathologic, and synovial fluid findings in 12 patients with the SAPHO syndrome: hidradenitis suppurativa (7), acne fulminans or conglobata (3), acneiform folliculitis (1) and palmoplantar pustulosis (1). Routine synovial fluid studies were performed in 6 patients, and light and transmission electron microscopic studies were performed in synovium in 2 patients and in bone in 1. The most common musculoskeletal manifestations included erosive or non-erosive oligoarthritis involving metacarpal phalangeal (MCP) and metatarsal phalangeal (MTP) joints as seen in 9 patients, sclerosis of the sacroiliac joints as seen in 5 patients, and osteitis pubis as seen in 1. Three patients had signs of skeletal hyperostosis. The patients with acne fulminans and acneiform folliculitis had chronic aseptic multifocal osteomyelitis. Synovial fluid was sterile in 7, mildly inflammatory in 5, and highly inflammatory in 2. Electron microscopic studies of synovium in 2 patients and of bone in 1 were not useful to detect microorganisms. Three African-American patients with hidradenitis suppurativa presented with pyoderma gangrenosum, and 2 of them had leukocytoclastic vasculitis, and a life threatening course unresponsive to antibiotics, corticosteroids and immunosuppressive therapy. SAPHO in the Americas is most severe in African-Americans with hidradenitis suppurativa, and it presents with heterogeneous musculoskeletal and cutaneous manifestations including erosive polyarthritis or oligoarthritis with nonspecific mild inflammatory fluid. Leukocytoclastic vasculitis and recalcitrant pyoderma gangrenosum were seen in 2 of our patients with the most severe hidradenitis suppurativa. SAPHO syndrome may present with clinical manifestations similar to those seen with seronegative spondyloarthropathies, but it has distinctive cutaneous, radiographic articular, and bone manifestations. Sites of chronic infection need aggressive antibiotic therapy and may need surgical resection.

Pathologic fracture of the femoral neck in a female soccer player.

We report a case of a healthy, young, female soccer player who developed progressive pain in her right hip. A bone cystic lesion was found in the right femoral neck and proximal femur. The lesion was considered a benign bone cyst and the patient was treated with injections of autologous bone marrow and grafting into the femoral neck. However, the cystic lesion did not heal. Subsequently, the patient fell and developed a fracture of the femoral neck that required internal fixation. The bone biopsy showed characteristic histologic features of fibrous dysplasia. A bone scan showed other areas of suspected dysplasia. Pamidronate therapy was given, and a reduction of the increased uptake was seen on bone scans. Fibrous dysplasia must be considered in the differential diagnosis of any cystic bone lesion.

Recent advances in crystal-associated arthritis (CAA)

É feita uma revisao das recentes aquisiçoes em artrites microcristalinas. Sao descritas as novas técnicas que podem representar métodos mais simples para a identificaçao dos cristais nos tecidos biológicos que a análise por difraçao de raios X e espectografia por infravermelho. É discutida a inflamaçao induzida por cristais à luz dos conhecimentos mais modernos. Sao descritas individualmente as diferentes formas de gota (por urato, pirofosfato, apatita, oxalato), num conceito clínico unicista. Finalmente, é feita referência a cristais comumente menos reconhecidos, como cristais de corticosteróides sintéticos de depósito, cristais de colesterol, de lipídios, cristais Charcot-Leyden, cristais de imunoglobulina e cristais derivados de hemoglobina que podem ter potencial flogístico. Tais cristais podem ser prontamente reconhecidos por microscopia polarizada compensada e muitos deles podem ser confundidos com cristais de urato e de pirofosfato e, ocasionalmente, podem vir a ser chave de importantes doenças sistêmicas