Current management of avascular necrosis of the metacarpal head: a comprehensive literature review.

BACKGROUND: Avascular necrosis (AVN) of the metacarpal head is a rare disease that may lead to progressive destruction of the metacarpophalangeal joint and hand function. This study aimed to describe the epidemiology, possible risk factors, clinical presentation, diagnostic workup, and treatment of the rare condition of avascular necrosis of the metacarpal head. METHODS: Articles were searched using the subject words "Dieterich disease","Mauclaire's disease", and "avascular necrosis of metacarpal head" in the PubMed and Scopus databases. Studies were retained for review after meeting the inclusion criteria. Those outcomes relevant to diagnose and assessing AVN of the metacarpal head and those related to curative management were extracted. RESULTS: The literature search revealed 45 studies with 55 patients. Although the aetiology of osteonecrosis has not been clearly delineated, AVN of the metacarpal head most commonly arises from trauma but other risk factors may also be involved. Plain radiographs are often negative and therefore likely to be missed. Early-stage osteonecrosis of the metacarpal head was best assessed using MRI. Given the rarity of this condition, there is no clear consensus on the treatment. CONCLUSIONS: Avascular necrosis of the metacarpal head should be considered in the differential diagnosis of painful metacarpophalangeal joints. An early understanding of this unusual disease will provide an optimal clinical outcome, restoring joint activity, and resolving pain. Nonoperative treatment cannot cure all patients. Surgical management is based on the patient and lesion characteristics.

DDX58(RIG-I)-related disease is associated with tissue-specific interferon pathway activation.

BACKGROUND: Singleton-Merten syndrome (SGMRT) is a rare immunogenetic disorder that variably features juvenile open-angle glaucoma (JOAG), psoriasiform skin rash, aortic calcifications and skeletal and dental dysplasia. Few families have been described and the genotypic and phenotypic spectrum is poorly defined, with variants in DDX58 (DExD/H-box helicase 58) being one of two identified causes, classified as SGMRT2. METHODS: Families underwent deep systemic phenotyping and exome sequencing. Functional characterisation with in vitro luciferase assays and in vivo interferon signature using bulk and single cell RNA sequencing was performed. RESULTS: We have identified a novel DDX58 variant c.1529A>T p.(Glu510Val) that segregates with disease in two families with SGMRT2. Patients in these families have widely variable phenotypic features and different ethnic background, with some being severely affected by systemic features and others solely with glaucoma. JOAG was present in all individuals affected with the syndrome. Furthermore, detailed evaluation of skin rash in one patient revealed sparse inflammatory infiltrates in a unique distribution. Functional analysis showed that the DDX58 variant is a dominant gain-of-function activator of interferon pathways in the absence of exogenous RNA ligands. Single cell RNA sequencing of patient lesional skin revealed a cellular activation of interferon-stimulated gene expression in keratinocytes and fibroblasts but not in neighbouring healthy skin. CONCLUSIONS: These results expand the genotypic spectrum of DDX58-associated disease, provide the first detailed description of ocular and dermatological phenotypes, expand our understanding of the molecular pathogenesis of this condition and provide a platform for testing response to therapy.

Singleton-Merten syndrome: A rare cause of femoral head necrosis.

Singleton-Merten syndrome (SMS) is a type I interferonopathy. In this report, we disclose the first-to the best of our knowledge-direct association of SMS with femoral head necrosis (FHN). The following case report presents the condition of a 38-year-old male suffering from SMS with FHN, characterized by acute symptoms and rapid disease progression. As per the recommendations of the Association Research Circulation Osseous (ARCO) and the S3-guidelines, we successfully treated the FHN with core decompression. Our histological results correlate with the changes described in medical literature in patients with SMS and MDA5-knockout in vivo experiments such as osteopenia, widened medullary cavity, and thin cortical bone. Moreover, the conducted immunohistochemistry shows strong CD56 positivity of the osteoblasts and osteocytes, as well as significant CD68 and CD163 positivity of the middle-sized osteoclasts. Collectively, these findings suggest an underlying syndrome in the FHN. A six-month post-operative follow-up revealed complete recovery with the absence of the initial symptoms and ability to resume normal daily activities. Taken together, our findings suggest that SMS is an additional cause of FHN in young adults. Early detection and adequate treatment using well-established joint-preserving techniques demonstrate a favorable improvement of the patient's clinical condition.

Unified mechanisms for self-RNA recognition by RIG-I Singleton-Merten syndrome variants.

The innate immune sensor retinoic acid-inducible gene I (RIG-I) detects cytosolic viral RNA and requires a conformational change caused by both ATP and RNA binding to induce an active signaling state and to trigger an immune response. Previously, we showed that ATP hydrolysis removes RIG-I from lower-affinity self-RNAs (Lässig et al., 2015), revealing how ATP turnover helps RIG-I distinguish viral from self-RNA and explaining why a mutation in a motif that slows down ATP hydrolysis causes the autoimmune disease Singleton-Merten syndrome (SMS). Here we show that a different, mechanistically unexplained SMS variant, C268F, which is localized in the ATP-binding P-loop, can signal independently of ATP but is still dependent on RNA. The structure of RIG-I C268F in complex with double-stranded RNA reveals that C268F helps induce a structural conformation in RIG-I that is similar to that induced by ATP. Our results uncover an unexpected mechanism to explain how a mutation in a P-loop ATPase can induce a gain-of-function ATP state in the absence of ATP.

Unusual cutaneous features associated with a heterozygous gain-of-function mutation in IFIH1: overlap between Aicardi-Goutières and Singleton-Merten syndromes.

Cutaneous lesions described as chilblain lupus occur in the context of familial chilblain lupus or Aicardi-Goutières syndrome. To date, seven genes related to Aicardi-Goutières syndrome have been described. The most recently described encodes the cytosolic double-stranded RNA receptor IFIH1 (also known as MDA5), a key component of the antiviral type I interferon-mediated innate immune response. Enhanced type I interferon signalling secondary to gain-of-function mutations in IFIH1 can result in a range of neuroinflammatory phenotypes including classical Aicardi-Goutières syndrome. It is of note that none of the patients with a neurological phenotype so far described with mutations in this gene was reported to demonstrate cutaneous involvement. We present a family segregating a heterozygous pathogenic mutation in IFIH1 showing dermatological involvement as a prominent feature, variably associated with neurological disturbance and premature tooth loss. All three affected individuals exhibited increased expression of interferon-stimulated genes in whole blood, and the mutant protein resulted in enhanced interferon signalling in vitro, both in the basal state and following ligand stimulation. Our results further extend the phenotypic spectrum associated with mutations in IFIH1, indicating that the disease can be confined predominantly to the skin, while also highlighting phenotypic overlap with both Aicardi-Goutières syndrome and Singleton-Merten syndrome.

Mutations in DDX58, which encodes RIG-I, cause atypical Singleton-Merten syndrome.

Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.

Chondromyxoid fibroma of the second metacarpal bone--a case report.

This report describes a chondromyxoid fibroma of the second metacarpal bone in a 32-year-old female patient. Chondromyxoid fibroma is a rare, benign, slow-growing bone tumor of cartilaginous origin. Tumor has a high recurrance rate. Our aim was to show successful treatment of a metacarpal chondromyxoid fibroma with wide resection and implantation of finger join endoprosthesis.

Purification of a lectin from Arisaema erubescens (Wall.) Schott and its pro-inflammatory effects.

The monocot lectin from the tubers of Arisaema erubescens (Wall.) Schott has been purified by consecutive hydrophobic chromatography and ion exchange chromatography methods. The molecular weight of this A. erubescens lectin (AEL) was determined to be about 12 kDa by high performance liquid chromatography (HPLC) and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) methods. AEL could agglutinate rabbit erythrocytes. The haemagglutination activity of AEL was only inhibited by asialofetuin, while monosaccharide did not react. Rat paw edema and neutrophil migration models were used to investigate the pro-inflammatory activity of AEL. AEL (100 and 200 µg/paw) could induce significant rat paw edema. In addition, AEL (100, 200 and 300 µg/mL/cavity) could induce significant and dose-dependent neutrophil migration in the rat peritoneal cavities. Besides, AEL at doses ranging from 100 to 300 µg/mL/cavity could significantly increase the concentration of nitric oxide (NO), prostaglandin E(2 )(PGE(2)) and tumor necrosis factor alpha (TNF-α) in peritoneal fluid. As compared with control animals, 75% depletion in the number of resident cells following peritoneal lavage did not reduce the AEL-induced neutrophil migration. However, pre-treatment with 3% thioglycollate which increased the peritoneal macrophage population by 201%, enhanced the neutrophil migration induced by AEL (200 µg/mL/cavity) (p < 0.05). Reduction of peritoneal mast cell population by chronic treatment of rat peritoneal cavities with compound 48/80 (N-methyl-p-methoxyphenethylamine with formaldehyde) did not modify AEL-induced neutrophil migration. The results provided the basis for identifying the toxic components of A. erubescens and AEL could be a new useful tool for pro-inflammatory research.

Manifestations, diagnosis and surgical treatment of enchondroma--own experience.

BACKGROUND: An enchondroma is a rather common benign tumour of bone that originates from cartilage.The course is usually benign but they have a tendency to recur and are sometimes invasive, especially when developing in long bones. The aim of the study was to analyze the manifestations and methods of treatment as well as to assess the results of surgical treatment in patients with enchondroma. MATERIAL AND METHODS: A total of 150 patients with enchondroma, including 90 women and 60 men aged 10-74 years, were treated in the Regional Trauma Surgery Hospital in Piekary Slaskie between 1998 and 2006. RESULTS: The tumours were mostly located in phalanges of the fingers--55 cases (37%), and metacarpal bones--21 cases (14%). Multiple locations were seen in 13 patients. A total of 170 surgical procedures were performed, mostly (120 procedures) tumour resections with bone graft implantation. A recurrence of enchondroma was observed in 17 patients (11%). There was also one case of malignant transformation in to a chondrosarcoma. CONCLUSION: Total resection of the enchondroma combined with spongy bone grafting is the main treatment of chondroma.

The effects of sympathetic outflow on upregulation of vanilloid receptors TRPV(1) in primary afferent neurons evoked by intradermal capsaicin.

The vanilloid receptor TRPV(1) is a key nociceptive molecule located in primary afferent nociceptive neurons in dorsal root ganglia (DRG) for initiating neurogenic inflammation and pain. Our recent study demonstrates that up-regulation of TRPV(1) receptors by intradermal injection of capsaicin is modulated by activation of the protein kinase C (PKC) cascade. Neurogenic inflammation and pain resulting from capsaicin injection are sympathetically dependent, responding to norepinephrine, adenosine 5'-triphosphate (ATP) and/or neuropeptide Y released from sympathetic efferents. In a rat model of acute neurogenic inflammatory pain produced by capsaicin injection, we used immunofluorescence and Western blots combined with pharmacology and surgical sympathectomies to analyze whether the capsaicin-evoked up-regulation of TRPV(1) in DRG neurons is affected by sympathetic outflow by way of activating the PKC cascade. Sympathetic denervation reduced significantly the capsaicin-evoked expressions of TRPV(1), calcitonin gene-related peptide and/or phosphorylated PKC and their co-expression. These reductions could be restored by exogenous pretreatment with an analog of ATP, alpha,beta-methylene ATP. Inhibition of PKC with chelerythrine chloride prevented the ATP effect. Consistent results were obtained from experiments in which capsaicin-evoked changes in cutaneous inflammation (vasodilation and edema) were examined after sympathetic denervation, and the effects of the above pharmacological manipulations were evaluated. Our findings suggest that the capsaicin-evoked up-regulation of TRPV(1) receptors in DRG neurons is modulated sympathetically by the action of ATP released from sympathetic efferents to activate the PKC cascade. Thus, this study proposes a potential new mechanism of sympathetic modulation of neurogenic inflammation.

Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells.

Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostin was found to differentially regulate the apoptosis, proliferation, alpha smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.

Invasive cutaneous angiomatosis and thrombocytopenia in a cat.

CASE DESCRIPTION: A 9-year-old 6.9-kg (15.18-lb) castrated male Siamese cat was evaluated because of a 3-year history of repeated hemorrhage from the right metacarpal pad. CLINICAL FINDINGS: Physical examination findings were unremarkable except for a 2-mm-diameter erosion of the right metacarpal pad. A CBC revealed marked thrombocytopenia. Serum biochemical analyses, retroviral screening, thoracic radiography, and abdominal ultrasonography revealed no abnormalities. Via ultrasonographic examination, the vasculature in the right metacarpal pad appeared increased, compared with that of the left pad; an aberrant arterial plexus that was confined to the metacarpal pad was identified via arterial angiography. TREATMENT AND OUTCOME: Surgical resection of the metacarpal pad (without digital pad transposition) with primary closure was performed. Histologic evaluation of the pad tissue revealed invasive cutaneous angiomatosis. The incision healed without complications, and limb function was considered normal. Administration of prednisone (2 mg/kg [0.91 mg/lb], PO, q 24 h) was initiated 4 weeks prior to surgery to treat suspected immune-mediated thrombocytopenia and continued afterwards with a tapering dosage. Platelet count was within reference limits 4 months after surgery; at 12 months, there was no evidence of recurrence of abnormal vasculature in the right metacarpal pad region. CLINICAL RELEVANCE: Complete resection of the metacarpal pad (without pad transposition) resulted in successful and well-tolerated treatment of cutaneous angiomatosis of the metacarpal pad of a cat. Recurrence of abnormal vasculature was not evident at a 12-month follow-up examination. Thrombocytopenia is commonly associated with vascular anomalies in humans and may have been a contributing factor in this cat.

Use of computed tomography to diagnose new bone formation associated with desmitis of the proximal aspect of the suspensory ligament in third metacarpal or third metatarsal bones of three horses.

CASE DESCRIPTION: 3 horses with lameness localized to the proximal aspect of the metacarpus or metatarsus. CLINICAL FINDINGS: All horses had evidence of problems that originated from the proximal aspect of the suspensory ligament (PASL), including signs of pain on palpation, positive results of diagnostic nerve blocks, ultrasonographic detection of enlargement and diffuse areas of reduced echogenicity in the proximal region of insertion of the ligament, and radiographic detection of increased mineral opacity in the proximal aspect of the metacarpus or metatarsus. Desmitis of the PASL was diagnosed in each horse; however, conservative treatment failed to improve the lameness. The horses were taken to surgery for splitting of the PASL and osteostixis of the proximal aspect of the third metacarpal or metatarsal bone. At that time, the proximal aspect of the metacarpus or metatarsus was evaluated via computed tomography (CT), which identified new bone formation at the proximal aspect of the third metacarpal or metatarsal bone that had not already been identified. TREATMENT AND OUTCOME: In all horses, the newly formed bone was removed surgically under radiographic and CT guidance, and the splitting and osteostixis that had been planned were performed. After rehabilitation, all horses returned to full training at 6 months after surgery. All horses responded well to the surgical treatment and were sound 8 months afterward. CLINICAL RELEVANCE: Use of CT imaging should be considered in lame horses with pain associated with the proximal aspect of the third metacarpal or metatarsal bones that does not improve with conservative treatment.

Exercise-induced metacarpophalangeal joint adaptation in the Thoroughbred racehorse.

Repetitive bone injury and development of stress fracture is a common problem in humans and animals. The Thoroughbred racehorse is a model in which adaptive failure and associated development of stress fracture is common. We performed a histologic study of the distal end of the third metacarpal bone in two groups of horses: young Thoroughbreds that were actively racing (n = 10) and a group of non-athletic horses (n = 8). The purpose of this study was to determine whether development of articular microcracks was associated with specific alterations to subchondral plate osteocytes. Morphometric measurements were made in five regions of the joint surface: lateral condyle, lateral condylar groove, sagittal ridge, medial condylar groove, and medial condyle. The following variables were quantified: hyaline cartilage width; calcified cartilage width; the number of tidemarks; microcrack density at the articular surface; blood vessel density entering articular cartilage; the presence of atypical bone matrix in the subchondral plate; bone volume fraction; and osteocyte density. Adaptation of articular cartilage was similar in both groups of horses. Vascularization of articular cartilage was increased in the group of non-athletic horses. Microcracks, which typically had an oblique orientation to the joint surface, were co-localized with blood vessels, and resorption spaces. Microcracking was increased in the condylar grooves of athletic horses compared with the other joint regions and was also increased compared with the condylar groove regions of non-athletic horses. Coalescence of microcracks also led to development of an intracortical articular condylar stress fracture in some joints and targeted remodeling of affected subchondral plate. The subchondral plate of the condyles in athletic horses was sclerotic, and contained atypically stained bone matrix with increased numbers of osteocytes with atypical morphology. However, osteocyte numbers were not significantly different between groups. We conclude that differences in site-specific microdamage accumulation and associated targeted remodeling between athletic and non-athletic horses are much greater than differences in subchondral osteocyte morphology. However, the presence of atypical subchondral bone matrix in athletic horses was associated with extensive osteocyte loss. Although osteocyte mechanotransduction is considered important for functional adaptation, in this model, adaptation is likely regulated by multiple mechanotransduction pathways.

The evolution and refinements of the distally based dorsal metacarpal artery (DMCA) flaps.

Distally based DMCA flaps are well established in reconstructive hand surgery. They comprise the dorsal flap described by Quaba and the DMCA flaps described by Earley, Milner and others. The most frequent indications for these flaps are soft tissue defects of the dorsum of the proximal phalanx and the total length of the finger. Since its introduction several modifications have been developed to match specific defect requirements; these include: the development of pure fascial DMCA flaps, the use of DMCA flaps in dorsally grafted burned hands and modifications in design to avoid 'tunnelling' and to permit skin-skin defect closure. The purpose of this article is to provide an overview of the evolution and refinements of the DMCA flaps based on the experience of a single centre. The DMCA flaps provide one stage coverage of excellent quality with independent vascularisation and permit primary closure of the recipient site without sacrificing relevant arteries (e.g. proper digital artery). However, the DMCA flaps also possess drawbacks, for example, apart from the fact that this technique is quite demanding, possible hair growth and a visible scar on the exposed dorsal part of the hand present aesthetic problems for some patients. Despite these limitations, DMCA flaps are considered to be extremely useful.

Hemophilic pseudotumor.

Bleeding diatheses are a hallmark of hemophilia. Hemophilic pseudotumor results from multiple episodes of hemorrhage into bones or soft tissue spaces. It is uncommon and is seen in severe cases of hemophilia only 1-2% of the time. Complications and symptoms arise due to pain and/or compression of surrounding structures. Pathologic fractures can be associated with intraosseous lesions and can result from bone destruction or resorption due to the chronic pressure of an osseous hemorrhage. Radiographs may demonstrate expansile lesions of the bones or increased soft tissue density that may be associated with extra osseous lesions. Bleeding may also occur within the joint space. These intra-articular hemorrhages can, over time, result in hemophilic arthropathy. The following case report demonstrates both an expansile lesion of a metacarpal as well as hemophilic knee arthropathy in an 11 year old.

[Osteomyelitis of the carpus and metacarpus]. / Osteomyelitis der Mittelhand- und Handwurzelregion.

AIM: Because of the low prevalence, there is poor evidence on the effective management of bone and joint infections of the carpus and metacarpus. We therefore studied the outcomes of patients undergoing surgical treatment at our department. METHOD: We conducted a retrospective study on all patients operated on because of osteomyelitis of the carpus and metacarpus between January 1998 and June 2004. Main study endpoint were the infection control rate at end of treatment and at time of follow-up. RESULTS: Of eleven subjects (nine men, two women) with a median age of 43 years (range, 19 to 79 years) serial débridement with temporary wound closure and surgical fixation proved successful in ten cases. We identified causative pathogens in ten cases (S. aureus: n = 3, P. aeruginosa: n = 3, mixed: n = 4) by intraoperative biopsy. Eight subjects received local or free tissue flaps. A 73 year old man died in hospital. Follow-up information was available for eight patients after a median of 19.5 months (range: 3 to 61 months). Seven of them did not show signs of recurrent infection. CONCLUSION: Adhering to accepted standards of treating osteomyelitis, satisfactory control rates in carpal and metacarpal infection can be achieved while salvaging the hand.

Osseous sarcoidosis of the hand: pathologic analysis and review of the literature.

A destructive granulomatous process involving the right fifth metacarpal and the soft tissues of the right thumb and nose of an African-American woman without pulmonary disease is described. The initial biopsy examination of the metacarpal showed caseating and noncaseating granulomata. After a fifth-ray amputation the disease progressed, leading to the referral of the patient to our institution. A biopsy examination of this recurrence showed a predominance of solid noncaseating granulomata. The diagnosis of sarcoidosis was made on the basis of the morphology of the granulomata and by exclusion of infectious and neoplastic causes. Steroid therapy has resulted in cessation of clinical and radiographic disease progression at a 3-year clinical follow-up evaluation.