Characterisation of the inflammatory response in Dupuytren’s disease

Background: Dupuytren’s disease is characterised by fibrotic nodule and cord formation in the palmar aponeurosis. The pathophysiology of the disease is still unknown, although cell stress and subsequent activation of immune mechanisms seems to be crucial. Materials and methods: Surgically obtained tissue and blood samples of 100 Dupuytren patients were processed by immunohistochemistry, flow cytometry, as well as immunoscope analysis. Macroscopically normal aponeurotic tissue served as control. Results: Locally, microvascular alterations and massive infiltration by mononuclear cells (CD3+, CD4?>?CD8, CD45RO?>?CD45RA, S100 protein, CD56, CD68, scarce CD19 and mast cells) forming perivascular clusters were found in DD tissue. Cytokine profiling of fibromatosis tissue-derived T-cells showed a Th1/TH17-weighted immune response. Immunoscope analysis revealed a restricted T-cell receptor α/β repertoire pointing to an (auto)antigen-driven process. Conclusion: The striking accumulation of immune cells, expression of leukocyte adhesion molecules, as well as pro-inflammatory and pro-fibrotic cytokines near markedly narrowed vessels supports the theory that the abnormal proliferation of fibroblasts and production of extracellular matrix proteins in DD seems to be related to immune-mediated microvascular damage. The restricted T-cell receptor repertoire of intra-lesional T-cells points to an antigen-driven process. T-cells seem to play an important role in the development of Dupuytren’s disease.     

Dupuytren’s disease – the story of an eponym

December 5, 1831, baron Guillaume Dupuytren presents at the surgical clinics of the Hotel-Dieu of Paris a report upon "an entirely new subject, with a new theory and a new method of treatment for a disease generally regarded as incurable". The patient presented had a permanent contraction of the ring finger and adjacent fingers of both hands, which appeared spontaneously without any injury or previous illness. Dupuytren explains he had the opportunity to dissect the hand of a man who died after having had a contraction of the fingers for many years. He defines the cause of the contraction to be the palmar fascia. He describes the operative treatment: aponeurotomy by a transverse incision. "Probably many surgeons (Cline 1808, Astley Cooper 1822) were aware of the palmar aponeurosis producing this condition before Dupuytren's lecture". "Thoroughness of his demonstration, the brilliance of the presentation and the supremacy of his surgical authority combined to link permanently the name of Dupuytren with this hand deformity" (J. Hueston).     

Dupuytren’s disease of ring and little finger

Objective  Resection of fibrous digitopalmar connective tissues to improve finger function. Indications  Dupuytren’s disease in Tubiana’s stage >III. Partial fasciectomy: at any age, for localized involvement, unlimited degree of contracture, and for recurrences. Complete fasciectomy: extension lag <45° of an individual finger, favorable skin condition, and progressing Dupuytren’s disease. Contraindications  Poor general health. State after stroke. Infection or eczema of hand. Excessive alcohol intake. Uncooperative patient. Relative: HIV infection. Surgical Technique  Antegrade dissection of the fibrous tissue from palm to distal interphalangeal joint through a Y-shaped palmar incision or longitudinal digital incision interrupted by Z-plasties at the level of flexion creases. Dissection starts at the radial healthy side. For partial fasciectomy, the fibrous tissue is removed including a safety margin. During complete fasciectomy, the entire triangular palmar fascia including the vertical septae is excised. The so-called open palm technique is a particular form of a partial fasciectomy whereby transverse incisions are not closed as opposed to longitudinal incisions which are always sutured. Results  In a prospective study, 48/239 patients were followed up >2 years. Recurrence rate was 39.7% while hand function improved by 70–86% in ulnar type. Complications observed in a retrospective study (1982–1991) of 566 patients (two thirds partial, one third complete fasciectomy): wound healing disturbance 3%, hematoma 2.5%, vessel injury 1.2%, nerve injury 1.8%, infection 0.7%, persisting edema 0.7%, scar contracture 0.2%. 87% of all recurrences appeared within 24 months. Their incidence after 2–10 years varied after partial or complete fasciectomy between 12.5 and 66%, and 21.4 and 39.7%, respectively. Only a small percentage of these needed a revision.     

Postoperative management of Dupuytren’s disease with topical nitroglycerin

Dupuytren’s contracture remains a significant clinical challenge due to associated complications and a recurrence rate of up to 60%. Commonly, the operated skin tends to rebuild scar in the area of surgery. Assuming local ischemia as an etiological factor, two cases in which topical nitroglycerin was used following surgical treatment of Dupuytren’s disease are presented. In these patients, no raised scar formation developed during healing. At least six months after surgery, disease recurrence was not noted and the patients and surgeon reported improved skin quality. In the present study, the use of topical nitroglycerin, a local vasodilator, appeared to prevent recurrent scar formation, possibly through prevention of local ischemia. Further study and follow-up is necessary.     

Phlegmonous-infection in first degree Dupuytren’s disease

Dupuytren’s disease belongs to the group of so called fibromatoses and is considered to be a non infectious disease. Since first degree Dupuytren’s disease is generally not operated upon, we want to report the unexpected finding of phlegmonous-abcessing infection in nodules in Dupuytren’s disease in a 61 year old patient, who was treated surgically because of complaining painful symptoms in first degree nodules in his palm without clinically visible signs of infection.     

Role of the HLA System in the Pathogenesis of Dupuytren’s Disease

Dupuytren's disease (DD) is a familial, fibroproliferative, irreversible, and progressive disease of the palmar fascia, yet with unknown etiology. However, there is compelling evidence which has consistently suggested a genetic ethiopathogenesis given the high occurrence among the Northern European extraction, familial nature, and demonstration of concordance in twins. DD is an incurable, recurrent, and potentially debilitating disease with limited and ineffective treatments. Although a number of possible candidate genes have been investigated including matrix metalloproteinases (MMPs) and transforming growth factor-beta (TGF-β) genes, as yet, no consistent genetic biomarker has been identified for DD. The highly polymorphic human leukocyte antigen (HLA) region is an ideal biomarker target. There have been some coherent data within the literature to suggest a genotype to phenotype association between certain HLA loci and a number of fibrotic disorders such as keloid and scleroderma, markedly with class II molecules and disease pervasiveness and clinical progression. The aim of this review, therefore, was to investigate the evidence indicative of both positive and negative associations between particular HLA alleles and DD. There is a clear association with specific HLA alleles and predilection or protection to DD, though there is a pressing need for further supportive data. The most promising of links to the HLA region in terms of a definitive genetic biomarker is with the class II HLA-DR loci. This paper presents a detailed account of the immunogenetic component of DD and explores the possible mechanisms of association between specific HLA molecules and susceptibility to DD.     

Dupuytren’s disease: limited fasciectomy,night splinting,and hand exercises—long-term results

European Journal of Orthopaedic Surgery & Traumatology - Dupuytren’s contracture (DC) is a fibroproliferative disorder of palmar fascia that causes flexion contractures of one or more...     

Castleman’s disease of the pleura

Castleman’s disease is a rare benign disease of the lymph nodes. Its origin from the pleura is rare. Surgical excision, when feasible, appears to provide good results. We encountered a patient who had the disease arising from the parietal pleura. We present the clinical scenario, investigations, and our management of the patient.     

Castleman’s disease of the spleen

Introduction: Castleman’s disease (CD), also known as giant or angiofolicular lymphoid hyperplasia or lymphoid hamartoma, is a group of atypical lymphoproliferative disorders that share common lymph node histological features and may be localized either to a single lymph node (unicentric) or occur systemically (multicentric).

Patient and Method: Herein, we present a rare case of a of 75-year-old female patient who was referred to our department and after a thorough work-up, underwent splenectomy with synchronous resection of an accessory spleen, splenic artery lymph nodes, and splenic hilar lymph nodes due to splenic involvement in a multicentric CD.

Results: The pathology of the specimens led to the conclusion that it was a case of polycentric HHV-8-positive CD, affecting the spleen, the accessory spleen, and the lymph nodes.

Conclusions: Incidence of this rare condition is believed to be approximately 0.001–0.05%. CD has been linked to the human immunodeficiency virus (HIV), human herpes virus 8 (HHV-8), and is associated with malignancies. The pathogenesis mechanism is considered to be a dysregulation and hypersecretion of cytokines, either idiopathic or secondary to a viral infection, with the latter considered the most frequent. Solid organ involvement is very rare as is splenic involvement.     

Morphological patterns of the pretendinous cord in Dupuytren’s disease: a predictor of clinical outcome?

The morphology of the pretendinous cord in Dupuytren’s disease is poorly described in vivo and especially with respect to recurrence after treatment. This prospective study was designed to describe the morphology of Dupuytren’s cords by ultrasound and to identify possible correlation between the ultrasonographic characteristics of these cords and the clinical outcomes two years after treatment. Thirty-nine patients with a contracture of at least 20° in the metacarpophalangeal (MCP) joint, who were scheduled for local treatment by either injectable collagenase clostridium histolyticum (CCH) or percutaneous needle fasciotomy (PNF), were examined by ultrasound. The echogenicity and position of the pretendinous cords in relation to flexor tendons and neurovascular bundles were categorized. The structure of the cords was described and characterized as predominantly nodular or fibrillar. All 39 patients were assessed clinically after two years. A majority of the patients (84%) had cords with nodular components, and six patients (16%) had fibrillar cords. After two years, the clinical results were compared to the ultrasonographic findings before treatment. Three patients had recurrent contracture, and a retrospective analysis showed that all of these patients had cords with mixed echogenicity and nodules before treatment. Fifteen patients had a palpable pretendinous cord, and all but one of these had cords with mixed echogenicity and nodular structure before treatment. This pilot study indicates that some ultrasonographic features of the Dupuytren’s cord, such as mixed echogenicity and nodular structure, may predict recurrence after minimally invasive treatment for Dupuytren’s contracture. However, a larger study in correlation with histological examination of the excised cords would be necessary to confirm the pathoanatomical significance of these ultrasonographic features.     

Examining the efficacy and maintenance of contracture correction after collagenase clostridium histolyticum treatment for Dupuytren’s disease

Background

This study examined the efficacy, complications, and contracture recurrence in patients who received injectable collagenase clostridium histolyticum (CCH) for Dupuytren’s-induced metacarpophalangeal (MP) and proximal interphalangeal (PIP) joint contractures.

Methods

A retrospective chart review at one center compared the degree of MP and PIP joint contracture pre-injection, post-cord rupture, and at final follow-up after a minimum duration of 6 months. Recurrence was defined as a 20 ° or greater increase in contracture above the minimum value achieved.

Results

Of 102 eligible patients, 48 patients (47 %) (31 males, 17 females) were available for review. 53 digits and 64 joints (46 MP joints and 18 PIP joints) were studied. The mean patient age was 66 years (range, 48–87 years) and mean follow-up duration was 15 months (range, 6 to 25 months). The mean MP joint contracture was 51 ± 20 ° at baseline, 4 ± 8 ° post-cord rupture, and 9 ± 15 ° at latest follow-up. The mean PIP joint contracture was 39 ± 23 ° at baseline, 14 ± 14 ° at cord rupture, and 29 ± 20 ° at latest follow-up. Of the 46 MP joints and 18 PIP joints, 11 MP (24 %) and 7 (39 %) PIP joints met the recurrence criteria. Of 102 patients, 1 patient had a small finger flexor tendon rupture.

Conclusions

Despite the dramatic initial reduction in contracture, recurrence developed in a high proportion of patients over the study period. While initially effective, CCH may not provide durable contracture reduction. However, CCH remains a viable nonsurgical treatment for Dupuytren’s disease.     

Calcium-dependent signaling in Dupuytren��s disease

Background  

Previous studies suggest that Dupuytren’s disease is caused by fibroblast and myofibroblast contractility. Cell contractility in smooth muscle cells is caused by calcium-dependent and calcium-independent signaling mechanisms. In the calcium-dependent pathway, calcium/calmodulin activates myosin light chain kinase (MLCK). In this study, the effects of calcium/calmodulin inhibition with the FDA-approved drug fluphenazine on Dupuytren’s fibroblast contractility and MLCK expression were tested.     

Percutaneous fasciotomy for the treatment of Dupuytren��s disease��a systematic review

Background  

Dupuytren’s disease is described as a thickening of the palmar fascia. It typically affects men of Northern European descent in their fifties. The disease process starts as a nodule at the distal palmar crease that progressively gives rise to a cord invading distally toward the finger. Historically, different treatments have been described. Our purpose was to perform a meta-analysis of the evidence published on the percutaneous fasciotomy (PCF) treatment.     

Survey of hand surgeons’ and therapists’ perceptions of the benefit of common surgical procedures of the hand

Objective: The objectives of this survey were (1) to study if surgeons’ perceptions of the benefit of six surgical procedures differ if they consider themselves as patients instead of treating a patient, (2) to evaluate the role of five predetermined factors that may influence decision-making, and (3) to assess how uniformly hand surgeons and hand therapists perceive the benefits of the surgical treatments.

Methods: The members of the national societies for Hand Surgery and Hand Therapy were asked to participate in the survey. Six patient cases with hand complaint (carpal tunnel syndrome, flexor tendon injury, dorsal wrist ganglion, thumb amputation, boxer’s fracture, and mallet fracture) and a proposed operative procedure were presented, and the respondents rated the procedures in terms of the expected benefit. Half of the surgeons were advised to consider themselves as patients when filling out the survey.

Results: A survey was completed by 56 surgeons (61%) and 59 therapists (20%). Surgeons who considered themselves as patients had less confident perception on the benefit of carpal tunnel release compared with surgeons, who considered treating patients. Hand surgeons and hand therapists had similar perception of the benefits of surgery. The expected functional result was regarded as the most important factor in directing the decision about the treatment.

Conclusions: Surgeons tended to be more unanimous in their opinions in cases, where there is limited evidence on treatment effect. The agreement between surgeons and therapists implies that the clinical perspectives are similar, and probably reflect the reality well.     

Surgical outcome of Dupuytren’s disease—no higher self-reported recurrence after segmental fasciectomy

A single-center survey on the patients’ perception of recurrence after Dupuytren’s surgery was conducted. To evaluate the impact of surgical techniques on self-reported recurrence rates, a retrospective analysis of 216 surgically treated patients with a minimum 2-year follow-up was conducted using a postal questionnaire. Reported recurrence rates were somewhat lower in segmental fasciectomy (43%), which was performed in 39% of the patients compared to an overall reported recurrence rate of 54% in all surgical procedures. In total fasciectomy with skin resection and grafting, patients reported a surprisingly high recurrence rate of 63%. By taking the prognostic value of diathesis into account, the difference in recurrence rates between surgical techniques was not statistically significant. Nevertheless, no higher recurrence risk in segmental fasciectomy was noticed and total fasciectomy with or without skin resection did not appear to guarantee indefinite results. At this point, surgical treatment in Dupuytren’s disease is confined to correcting contractures, without curing the patients. Therefore, unless segmental fasciectomy is not feasible due to the severity of the contractures, we suggest to always consider minimal invasive surgery as a surgical option in the treatment of Dupuytren’s disease.     

Dupuytren’s Contracture – Current Concepts

Dupuytren’s contracture is a common condition that has the potential to be debilitating. It presents in a variety of manners and can be mild or more aggressive in its progression. There are a large number of management options currently available. In this review of the evidence, non-operative and operative management options are examined, with a consideration of post-operative rehabilitation and complications. A summary of the current concepts in the management of Dupuytren’s contracture is presented.     

Castleman’s disease of the mesorectum: Report of a case

Castleman’s disease is a benign lymphoid proliferative disorder, which most commonly presents as a solitary mass in the mediastinum, although extrathoracic sites have been reported in the neck, axilla, pelvis, mesentery, pancreas, and retroperitoneum. We report a case of asymptomatic, isolated Castleman’s disease in the mesorectum, which is extremely rare. The patient was a 34-year-old woman who underwent investigations for vaginal spotting. A presacral mass was located on the left side of the rectum, 10 cm from the anal verge. Contrast-enhanced computed tomography showed a large, well-demarcated, strongly enhancing mass with internal radiating septa in the mesorectum. The mass was well circumscribed and isointense to muscle on T1-weighted magnetic resonance imaging, appearing as a slightly hyperintense mass on T2-weighted imaging. We performed laparoscopic mesorectal mass excision, and histological examination revealed features typical of the hyaline-vascular type of Castleman’s disease. Thus, when a mesorectal mass is being investigated, Castleman’s disease should be considered in the differential diagnosis.