Pharmacological Management of Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome Syndrome: A Proposal of a Treatment Algorithm.

ABSTRACT: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic disease with marked clinical and radiological heterogeneity. It is characterized by a combination of dermatological and osteoarticular manifestations. The treatment of SAPHO syndrome is not yet codified. It includes several therapeutic options such as anti-inflammatory drugs, bisphosphonates, antibiotics, conventional disease-modifying antirheumatic drugs, and biological treatment.This article aims to provide an updated review of the different pharmacological options for SAPHO syndrome. We also propose a therapeutic algorithm for the management of this disease.

Skull Base Primary Extracranial Meningioma with Hyperostosis in a Small Mixed-Breed Dog.

A 7 yr old female spayed Chihuahua-terrier mix was presented for a progressive dry, hacking cough over 9 mo, with dyspnea aggravated by eating and drinking. Computed tomography of the skull revealed a large mineral attenuating mass associated with the left skull base, without intracranial involvement. A modified ventral paramedian hypophysectomy approach along the medial aspect of the left ramus was used to approach the base of the skull. Ninety percent of the mass was debulked via high-speed pneumatic burr. Histopathology was consistent with hyperostosis originating from a primary extracranial meningioma (ECM), with the tissue staining positive for vimentin and negative for cytokeratin. The patient was symptom free for 9 mo before clinical signs returned because of tumor recurrence and was euthanized 11 mo postoperation because of diminished quality of life. ECM is uncommonly reported in the dog, and to the authors' knowledge has not previously been reported with hyperostosis or located along the skull base at the level of the tympanic bulla. Additionally, although hyperostosis predominantly occurs as diffuse bone thickening adjacent to a meningioma, proliferative focal hyperostosis is uncommon. Given the findings in this patient, ECM should be considered as a differential diagnosis for osseous skull base masses.

Challenges in the clinical diagnosis of psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic heterogeneous inflammatory musculoskeletal disease. The non-specific and often subtle manifestations make early diagnosis and subsequent treatment challenging. In the absence of diagnostic criteria and biomarkers, the diagnosis is often delayed leading to poor long-term outcomes. In addition, the differential diagnosis of a patient presenting with arthritis in the setting of skin psoriasis is wide due to symptom overlap with many other diseases. Peripheral arthritis, dactylitis, enthesitis and axial arthritis are the 4 domains of musculoskeletal involvement in PsA and careful examination of each domain by a rheumatologist is the first step for a correct diagnosis. Other extra-musculoskeletal features such as the presence of uveitis, inflammatory bowel disease, nail psoriasis and elevated acute phase reactants aid in the diagnosis of PsA. Screening patients with skin psoriasis using validated questionnaires might help in early diagnosis especially when coupled with imaging.

Hypertrophic osteopathy in a cat with cardiac interventricular septal defect.

A 3-year-old mixed-breed female cat was diagnosed with a ventricular septal defect of the heart through an echocardiogram. After a 9-month treatment, progressive and diffuse hard thickening of all limbs was observed, which on radiographic examinations, revealed a marked thickening of the long bones. The necropsy findings were limited to the appendicular skeleton and thoracic vertebrae, in addition to a severe cardiac interventricular septal defect and lung edema. The histological evaluation revealed severe replacement of the cortical bone by spongy bone in all bone fragments examined. This is the first report of hypertrophic osteopathy occurring in association with a cardiac malformation in a cat.

Subjects with diffuse idiopathic skeletal hyperostosis have an increased burden of coronary artery disease: An evaluation in the COPDGene cohort.

BACKGROUND AND AIMS: Diffuse idiopathic skeletal hyperostosis (DISH) is a common incidental finding on medical imaging and often thought to be benign. Our objective was to investigate whether DISH is associated with coronary artery disease as measured with the coronary artery calcification (CAC) score in a large cohort of current and former smokers. METHODS: In a subset of subjects from the COPDGene study, DISH was scored by a minimum of two independent readers if there were four adjacent levels of flowing osteophytes and a third reader adjudicated discrepancies. CAC was calculated using a modified Agatston method. Associations of DISH with the presence and extent of CAC were analyzed with and without adjustment for COPD and known atherosclerotic risk factors, including age, sex, race, diabetes, hypertension, high cholesterol, body mass index and smoking. RESULTS: DISH was present in 361 subjects (13.2%) from a total group of 2728. Median (interquartile range) Agatston was 81 (0-329) in DISH subjects compared to 0 (0-94 in subjects without DISH (p < 0.001). DISH prevalence was 8.8% in CAC = 0, 12.8% in CAC1-100, 20.0% in CAC100-400 and 24.7% in CAC.400. Subjects with DISH had a significantly higher risk of having coronary artery calcifications; OR [CI95%] 1.37[1.05-1.78] (p=0.019) after correction for age, gender, race, COPD and atherosclerotic risk factors. CONCLUSIONS: Subjects with DISH, a common musculoskeletal disorder involving bone formation anterior to the spine, have an increased burden of coronary artery disease, and therefore DISH may be a more relevant incidental finding than commonly thought.

Cribra orbitalia and porotic hyperostosis: A biological approach to diagnosis.

OBJECTIVES: Porotic lesions of the skull (cribra orbitalia and porotic hyperostosis) are one of the most common types of lesion identified in archaeological human bone and have also been found in hominins and non-human primates. Because of the frequency with which such lesions are found there has been extensive debate on the possible causes and whether they are linked, with much of the debate centering on anemia. The biological approach to diagnosis in paleopathology used by Don Ortner and recently proposed more formally as a technique to facilitate diagnosis in paleopathology by Simon Mays may offer a means of answering some of the questions surrounding these lesions. MATERIALS AND METHODS: A review was undertaken of biomedical information on changes in the distribution of marrow type and pattern of conversion of red and mixed marrow, and the potential for re-conversion of yellow marrow with age. The range and type of other conditions that might result in the development of porous lesions were also considered. RESULTS: Combining information from the biomedical literature on marrow type and patterns of conversion with age, with careful evaluation of the type and location of porous lesions in the skull and across the rest of the skeleton will assist in suggesting a diagnosis. DISCUSSION: A wide range of conditions can produce porous lesions in the cranial vault and the orbital roof, but due to anatomical structures and physiological factors such lesions are more likely to occur in the orbital roof. Anemia can produce lesions in both locations, but evidence of marrow expansion is required to confirm it as a cause.

Síndrome de Goldbloom: síndrome febril prolongado con disproteinemia. Caso clínico / Goldboom's syndrome: prolonged febrile syndrome with dysproteinemia. Case report

El síndrome de Goldbloom es una rara entidad clínica de etiología desconocida que ocurre casi exclusivamente en pediatría. Consiste en un síndrome febril prolongado con hiperostosis perióstica y disproteinemia, que, con frecuencia, simula una patología hematooncológica o linfoproliferativa. El diagnóstico se hace por exclusión de las diferentes causas de dolor de los huesos y se asocia a hipergammaglobulinemia, hipoalbuminemia, eritrosedimentación acelerada e imágenes radiológicas de periostitis. La sintomatología, la radiología y los parámetros de laboratorio remiten en un tiempo variable, que va, habitualmente, de los 3 a los 12 meses. Se presenta a un paciente de 6 años con dolores óseos difusos, hiperostosis perióstica, síndrome febril prolongado de 8 meses de evolución, pérdida de peso y reactantes de fase aguda elevados con disproteinemia (hipergammaglobulinemia e hipoalbuminemia). Debe considerarse el síndrome de Goldbloom en un paciente con las manifestaciones descritas luego de la exclusión de la patología infecciosa, hematooncológica e inflamatoria de otra causa.

Goldbloom syndrome is a rare clinical entity, of unknown etiology that happens almost exclusively in pediatric population. It is a prolonged febrile syndrome with periosteal hyperostosis and dysproteinemia, and often simulates an hematooncology or lymphoproliferative disease. The diagnosis is to rule out the different causes of bone pain associated with hypergammaglobulinemia, hypoalbuminemia, high erythrocyte sedimentation rate and periostitis at the radiographies. Symptomatology, radiology and laboratory parameters refer in a variable time, usually from 3 to 12 months. We report the case of a six-year-old boy with diffuse bone pain, prolonged febrile syndrome (of 8 months of evolution), weight loss and elevated acute phase reactants with dysproteinemia (hypergammaglobulinemia and hypoalbuminemia). Goldbloom syndrome should be considered in patients with prolonged febrile syndrome and cortical hyperostosis after the exclusion of infectious, lymphoproliferative or inflammatory disease.

[Goldboom's syndrome: prolonged febrile syndrome with dysproteinemia. Case report]. / Síndrome de Goldbloom: síndrome febril prolongado con disproteinemia. Caso clínico.

Goldbloom syndrome is a rare clinical entity, of unknown etiology that happens almost exclusively in pediatric population. It is a prolonged febrile syndrome with periosteal hyperostosis and dysproteinemia, and often simulates an hematooncology or lymphoproliferative disease. The diagnosis is to rule out the different causes of bone pain associated with hypergammaglobulinemia, hypoalbuminemia, high erythrocyte sedimentation rate and periostitis at the radiographies. Symptomatology, radiology and laboratory parameters refer in a variable time, usually from 3 to 12 months. We report the case of a six-year-old boy with diffuse bone pain, prolonged febrile syndrome (of 8 months of evolution), weight loss and elevated acute phase reactants with dysproteinemia (hypergammaglobulinemia and hypoalbuminemia). Goldbloom syndrome should be considered in patients with prolonged febrile syndrome and cortical hyperostosis after the exclusion of infectious, lymphoproliferative or inflammatory disease.

El síndrome de Goldbloom es una rara entidad clínica de etiología desconocida que ocurre casi exclusivamente en pediatría. Consiste en un síndrome febril prolongado con hiperostosis perióstica y disproteinemia, que, con frecuencia, simula una patología hematooncológica o linfoproliferativa. El diagnóstico se hace por exclusión de las diferentes causas de dolor de los huesos y se asocia a hipergammaglobulinemia, hipoalbuminemia, eritrosedimentación acelerada e imágenes radiológicas de periostitis. La sintomatología, la radiología y los parámetros de laboratorio remiten en un tiempo variable, que va, habitualmente, de los 3 a los 12 meses. Se presenta a un paciente de 6 años con dolores óseos difusos, hiperostosis perióstica, síndrome febril prolongado de 8 meses de evolución, pérdida de peso y reactantes de fase aguda elevados con disproteinemia (hipergammaglobulinemia e hipoalbuminemia). Debe considerarse el síndrome de Goldbloom en un paciente con las manifestaciones descritas luego de la exclusión de la patología infecciosa, hematooncológica e inflamatoria de otra causa.

Biopsy-proven multiple sclerosis in an adult patient with atypical craniometaphyseal dysplasia.

Craniometaphyseal dysplasia (CMD) is a rare condition characterised by progressive, diffuse hyperostosis of cranial and long bones, with compression of cranial nerves, linked to mutations in ANKH or GJA1 genes. Here we describe an adult case with clinical features of CMD, who developed cerebral expansive lesion of undetermined nature. Brain biopsy revealed active demyelinating lesions, consistent with multiple sclerosis. The genetic screening of target genes for CMD (ANKH and GJA1) resulted negative in this patient. The peculiar clinical association and the negativity of genetic analyses allow to hypothesise that other genetic causes, not already known, are responsible for the combination of these pathological conditions. Future studies aim to identify the genetic causes of CMD, which will be important to further understand the pathogenetic mechanism of this rare and invalidating disease.

Cutis laxa and excessive bone growth due to de novo mutations in PTDSS1.

The cutis laxa syndromes are multisystem disorders that share loose redundant inelastic and wrinkled skin as a common hallmark clinical feature. The underlying molecular defects are heterogeneous and 13 different genes have been involved until now, all of them being implicated in elastic fiber assembly. We provide here molecular and clinical characterization of three unrelated patients with a very rare phenotype associating cutis laxa, facial dysmorphism, severe growth retardation, hyperostotic skeletal dysplasia, and intellectual disability. This disorder called Lenz-Majewski syndrome (LMS) is associated with gain of function mutations in PTDSS1, encoding an enzyme involved in phospholipid biosynthesis. This report illustrates that LMS is an unequivocal cutis laxa syndrome and expands the clinical and molecular spectrum of this group of disorders. In the neonatal period, brachydactyly and facial dysmorphism are two early distinctive signs, later followed by intellectual disability and hyperostotic skeletal dysplasia with severe dwarfism allowing differentiation of this condition from other cutis laxa phenotypes. Further studies are needed to understand the link between PTDSS1 and extra cellular matrix assembly.

Transorbital endoscopic eyelid approach for resection of sphenoorbital meningiomas with predominant hyperostosis: report of 2 cases.

Sphenoorbital meningiomas (SOMs) are slow-growing tumors that originate from the sphenoidal wing and are associated with visual deterioration, extrinsic ocular movement disorders, and proptosis caused by hyperostosis of the lateral wall of the orbit. In some cases, the intracranial component is quite small or "en plaque," and the majority of the symptoms arise from adjacent hyperostosis. Craniotomy has traditionally been the standard of care, but new minimally invasive multiportal endoscopic approaches offer an alternative. In the current study, the authors to present their experience with the transorbital endoscopic eyelid approach for the treatment of 2 patients with SOMs and sphenoid wing hyperostosis. Clinical and radiological data for patients with SOMs who underwent a transorbital endoscopic eyelid approach were retrospectively reviewed. Surgical technique and clinical and radiographic outcomes were analyzed. The authors report the cases of 2 patients with SOMs and proptosis due to sphenoid wing hyperostosis. One patient underwent prior craniotomy to debulk the intracranial portion of the tumor, and the other had a minimal intracranial component. Both patients were discharged 2 days after surgery. MR images and CT scans demonstrated a large debulking of the hyperostotic bone. Postoperative measurement of the proptosis with the aid of an exophthalmometer demonstrated significant reduction of the proptosis in one of the cases. Persistence of intraconal tumor in the orbital apex limited the efficacy of the procedure in the other case. A review of the literature revealed 1 publication with 3 reports of the transorbital eyelid approach for SOMs. No measure of relief of proptosis after this surgery had been previously reported. The transorbital endoscopic approach, combined with endonasal decompression of the medial orbit, may be a useful minimally invasive alternative to craniotomy in a subset of SOMs with a predominantly hyperostotic orbital wall and minimal intracranial bulky or merely en plaque disease. In these cases, relief of proptosis and optic nerve compression are the primary goals of surgery, rather than gross-total resection, which may have high morbidity or be unachievable. In cases with significant residual intraconal tumor, orbital bone removal alone may not be sufficient to reduce proptosis.

Frontal Hyperostosis in the Patients of Craniosynostosis After Cranial Distraction Osteogenesis.

BACKGROUND: Conventional fronto-orbital advancement and distraction osteogenesis (DOG) have been used to treat craniosynostosis, both of which are considered effective. During the authors' practice, a phenomenon of frontal hyperostosis has been observed in the patients of craniosynostosis after DOG, which has yet to be reported in the literature. The purpose of this study is trying to identify the factors related to the phenomenon. MATERIALS AND METHODS: From 1997 to 2010, all patients of craniosynostosis undergoing DOG were reviewed. The patient's age at operation, consolidation period, numbers of distractor, distance of distraction, and duration from removal of the distractors to identification of the phenomenon on computed tomography were recorded. The phenomenon was considered positive when the hyperostosis appeared on the frontal bone, where it was neither the osteotomy site nor the previous position of distractor. RESULTS: A total of 61 patients were included in this study, including 26 syndromic and 35 nonsyndromic patients. Two syndromic and 6 nonsyndromic patients had the phenomenon. There was no statistical difference between the patients with and without the phenomenon in comparison with the age, number of the distractor, consolidation period, and the distance of distraction. CONCLUSION: Frontal hyperostosis happened in some patients of craniosynostosis after DOG. Although no significant difference was demonstrated, the incidence of hyperostosis was higher in nonsyndromic patients and the patients of hyperostosis had shorter distance of distraction in both syndromic and nonsyndromic groups. Although the definite cause was unknown, we should pay attention to the phenomenon after distraction.

Clinical and imaging mimickers of axial spondyloarthritis.

The first step in the diagnosis of a patient with suspected axial spondyloarthritis is to differentiate the signs and symptoms of the disease from other disorders, potentially manifesting with similar clinical and imaging features. This review examines diffuse idiopathic skeletal hyperostosis, osteitis condensans ilii, and other developmental and metabolic disorders that may mimic axial spondyloarthritis, highlighting the diagnostic caveats and discussing shared and distinguishing aspects of these conditions in order to improve the clinician's ability to set them apart.

Bacterial Osteomyelitis or Nonbacterial Osteitis in Children: A Study Involving the German Surveillance Unit for Rare Diseases in Childhood.

BACKGROUND: Although bacterial osteomyelitis (BO) is a commonly recognized diagnosis in pediatrics, it is often difficult to distinguish from nonbacterial osteitis (NBO). The goal of our study was to distinguish between the 2 disease entities and better define NBO. METHODS: Using the German Surveillance Unit for Rare Diseases in Childhood (Erhebungseinheit für Seltene Paediatrische Erkrankungen in Deutschland), this prospective study during a 5-year period captured 657 patients at first diagnosis of either BO (n = 378) or NBO (n = 279) while analyzing epidemiologic, clinical and radiologic data. RESULTS: BO was reported in 1.2 per 100,000 children with a higher prevalence in younger male patients (58%), and NBO was reported in 0.45 per 100,000 children. BO patients tended to present with fevers (68%), elevated inflammation markers (82%) and local swelling (62%) but a shorter course of symptoms than NBO patients. NBO patients presented in good general health (86%) and were more likely to have multifocal lesions (66%). Staphylococcus aureus was the most prominent pathogen (83%), with only one methicillin-resistant S. aureus reported. Complications ranged from arthritis adjacent to the lesion to hyperostosis and vertebral fractures. CONCLUSIONS: BO and NBO can be distinguished based on symptoms, associated diseases and inflammation markers. NBO should always be considered in pediatric patients presenting with bone lesions and pain, especially in young female patients presenting with good general health, minimal inflammation markers and multifocal lesions in the vertebrae, clavicle and sternum.

Hyperostosis Following Orbital Exenteration.

PURPOSE: To describe CT scan findings following orbital exenteration in 27 patients and to identify the factors involved in the development of post exenteration hyperostosis. METHODS: Noncomparative case series. The authors reviewed the charts of 27 patients ranging in age from 33 to 99 years, who underwent unilateral exenteration at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia and at the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil. Data regarding patient demographics, surgical procedure, clinical diagnosis, and preoperative and postoperative CT imaging of the orbits were obtained. The relationship between hyperostosis and postoperative time, gender, age, adjuvant radiotherapy, and cavity coverage was evaluated by multivariate stepwise logistic regression. RESULTS: Seventeen (73.9 %) orbits had postoperative orbital hyperostosis. No soft tissue masses were detected in the affected orbits except in 2 cases with tumor recurrence. The only factor associated with hyperostosis was immediate intraoperative socket rehabilitation (odds ratio = 0.13, 95% confidence interval: 0.01-0.89). There was an 87.0% lower chance of hyperostosis in patients whose socket was covered with musculocutaneous flaps. Sequential CT scans showed that orbital hyperostosis followed a specific pattern. Initially, bone thickening appeared as either uniform or undulating endo-osteal minimal thickening along the roof and then on the lateral and medial walls. More advanced hyperostosis had a laminated/lamellated appearance progressing to homogeneous and diffuse circumferential bone thickening. New bone formation and bone overgrowth were late findings. Hyperostosis extended to involve the adjacent facial bone, more obviously on the maxilla. Some patients had minimal thickening of the adjacent frontal and squamous temporal bone. Over-pneumatization of the paranasal sinuses was evident in all cases of hyperostosis. CONCLUSIONS: Development of hyperostosis following exenteration is not rare. Radiologists and surgeons should be aware of the need to monitor the orbital healing process closely to avoid misdiagnoses of tumor recurrence/radionecrosis or infection. Obliteration of the orbital cavity with musculocutaneous flaps significantly reduces the chances of bone hyperostosis.

Somatic AKT1 mutations cause meningiomas colocalizing with a characteristic pattern of cranial hyperostosis.

Somatic genetic mutations in meningiomas are associated with histologic subtypes, anatomical location, and grade. Concomitant hyperostosis occurs with some meningiomas and the pathogenesis is not well understood. Cranial hyperostosis and meningiomas are common in patients with Proteus syndrome, which is caused by a somatic activating mutation in AKT1 c.49G>A. This same mutation has also been found in 6-9% of sporadic non-syndromic meningiomas. Sixty-one patients with Proteus syndrome meeting clinical diagnostic criteria were evaluated at the NIH from 1997 to 2014. Of these 61, 52 had a somatic activating mutation (c.49G>A, p.Glu17Lys) in AKT1 confirmed from affected tissue samples. Photographs, physical examination and/or autopsy, X-rays, CT, and/or MRI scan of the head were reviewed in 29/52 patients. Of the 29 patients, the most common intracranial tumor was meningioma, all co-localizing with cranial hyperostosis, and diagnosed at younger ages than typical for isolated, non-syndromic meningiomas. These patients had progressive cranial overgrowth that consisted primarily of diploic space expansion, and was characterized by unilateral, parasagittal, and frontal bone involvement. We hypothesize that sporadic meningothelial and transitional subtype meningiomas are a forme fruste or microform of Proteus syndrome, and activation of the AKT/PI3K pathway drives hyperostosis in both non-syndromic, and Proteus-related meningiomas. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.