A retrospective study of 222 patients with newly diagnosed primary central nervous system lymphoma-Outcomes indicative for improved survival overtime.

Primary central nervous system lymphoma (PCNSL) is a rare disease with an incidence of 0.4/per 100,000 person-years. As there is a limited number of prospective randomized trials in PCNSL, large retrospective studies on this rare disease may yield information that might prove useful for the future design of randomized clinical trials. We retrospectively analyzed the data of 222 newly diagnosed PCNSL patients treated in five referral centers in Israel between 2001 and 2020. During this period, combination therapy became the treatment of choice, rituximab has been added to the induction therapy, and consolidation with irradiation was largely laid off and was mostly replaced by high-dose chemotherapy with or without autologous stem cell transplantation (HDC-ASCT). Patients older than 60 comprised 67.5% of the study population. First-line treatment included high-dose methotrexate (HD-MTX) in 94% of patients with a median MTX dose of 3.5 g/m2 (range 1.14-6 g/m2 ) and a median cycle number of 5 (range 1-16). Rituximab was given to 136 patients (61%) and consolidation treatment to 124 patients (58%). Patients treated after 2012 received significantly more treatment with HD-MTX and rituximab, more consolidation treatments, and autologous stem cell transplantation. The overall response rate was 85% and the complete response (CR)/unconfirmed CR rate was 62.1%. After a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival (OS) were 21.9 and 43.5 months respectively with a significant improvement since 2012 (PFS: 12.5 vs. 34.2 p = 0.006 and OS: 19.9 vs. 77.3 p = 0.0003). A multivariate analysis found that the most important factors related to OS were obtaining a CR followed by rituximab treatment and Eastern Cooperative Oncology Group performance status. The observed improvement in outcomes may be due to multiple components such as an intention to treat all patients regardless of age with HD-MTX-based combination chemotherapy, treatment in dedicated centers, and more aggressive consolidation with the introduction of HDC-ASCT.

Clinical outcomes and temporal trends of immunological and non-immunological rare diseases in adult kidney transplant.

BACKGROUND: Rare diseases (RDs) encompass many difficult-to-treat conditions with different characteristics often associated with end-stage renal disease (ESRD). However, data about transplant outcomes in adult patients are still lacking and limited to case reports/case series without differentiation between immunological/non-immunological RDs. METHODS: Retrospective analysis among all adult kidney transplanted patients (KTs) with RDs (RDsKT group) performed in our high-volume transplantation center between 2005 and 2016. RDs were classified according to the Orphanet code system differentiating between immunological and non-immunological diseases, also comparing clinical outcomes and temporal trends to a control population without RDs (nRDsKT). RESULTS: Among 1381 KTs, 350 patients (25.3%) were affected by RDs (RDsKTs). During a f/up > 5 years [median 7.9 years (4.8-11.1)], kidney function and graft/patient survival did not differ from nRDsKTs. Considering all post-transplant complications, RDsKTs (including, by definition, patients with primary glomerulopathy except on IgA nephropathy) have more recurrent and de-novo glomerulonephritis (14.6% vs. 9.6% in nRDsKTs; p = 0.05), similar rates of de-novo cancers, post-transplant diabetes, dysmetabolism, hematologic disorders, urologic/vascular problems, and lower infectious episodes than nRDsKTs (63.7% vs 72.7%; p = 0.013). Additional stratification for immunological and non-immunological RDsKTs or transplantation periods (before/after 2010) showed no differences or temporal trends between groups. CONCLUSIONS: Kidney transplant centers are deeply involved in RDs management. Despite their high-complex profile, both immunological and non-immunological RDsKTs experienced favorable patients' and graft survival.

Biomarkers in Rare Diseases.

There is no single global definition of a rare disease, and for different geographical areas the definition is based on the disease occurrence in that population [...].

Pediatric necrobiosis lipoidica: case report and review of the literature.

Necrobiosis lipoidica (NL) is a rare, granulomatous disease considered to be associated with diabetes. It is frequently seen in female and middle-aged patients and is rarely observed in children. We present a 14-year-old boy with poorly controlled type 1 diabetes who developed biopsy-proven NL. He had improvement, but not resolution of the plaque with improved glycemic control. Pediatric NL may be associated with diabetes and could be related to poor glycemic control. However, further investigation is warranted in this young population.

Deep Gluteal Syndrome: A Pain in the Buttock.

ABSTRACT: While buttock pain is a common complaint in sports medicine, deep gluteal syndrome (DGS) is a rare entity. DGS has been proposed as a unifying term referring to symptoms attributed to the various pain generators located in this region. While not all-inclusive, the diagnosis of DGS allows for focus on pathology of regionally associated muscles, tendons, and nerves in the clinical evaluation and management of posterior hip and buttock complaints. An understanding of the anatomic structures and their kinematic and topographic relationships in the deep gluteal space is pivotal in making accurate diagnoses and providing effective treatment. Because presenting clinical features may be unrevealing while imaging studies and diagnostic procedures lack supportive evidence, precise physical examination is essential in obtaining accurate diagnoses. Management of DGS involves focused rehabilitation with consideration of still clinically unproven adjunctive therapies, image-guided injections, and surgical intervention in refractory cases.

Multifactorial Rare Diseases: Can Uncertainty Analysis Bring Added Value to the Search for Risk Factors and Etiopathogenesis?

Uncertainty analysis is the process of identifying limitations in knowledge and evaluating their implications for scientific conclusions. Uncertainty analysis is a stable component of risk assessment and is increasingly used in decision making on complex health issues. Uncertainties should be identified in a structured way and prioritized according to their likely impact on the outcome of scientific conclusions. Uncertainty is inherent to the rare diseases (RD) area, where research and healthcare have to cope with knowledge gaps due to the rarity of the conditions; yet a systematic approach toward uncertainties is not usually undertaken. The uncertainty issue is particularly relevant to multifactorial RD, whose etiopathogenesis involves environmental factors and genetic predisposition. Three case studies are presented: the newly recognized acute multisystem inflammatory syndrome in children and adolescents associated with SARS-CoV-2 infection; the assessment of risk factors for neural tube defects; and the genotype-phenotype correlation in familial Mediterranean fever. Each case study proposes the initial identification of the main epistemic and sampling uncertainties and their impacts. Uncertainty analysis in RD may present aspects similar to those encountered when conducting risk assessment in data-poor scenarios; therefore, approaches such as expert knowledge elicitation may be considered. The RD community has a main strength in managing uncertainty, as it proactively develops stakeholder involvement, data sharing and open science. The open science approaches can be profitably integrated by structured uncertainty analysis, especially when dealing with multifactorial RD involving environmental and genetic risk factors.

Identifying disease-causing mutations in genomes of single patients by computational approaches.

Over the last decade next generation sequencing (NGS) has been extensively used to identify new pathogenic mutations and genes causing rare genetic diseases. The efficient analyses of NGS data is not trivial and requires a technically and biologically rigorous pipeline that addresses data quality control, accurate variant filtration to minimize false positives and false negatives, and prioritization of the remaining genes based on disease genomics and physiological knowledge. This review provides a pipeline including all these steps, describes popular software for each step of the analysis, and proposes a general framework for the identification of causal mutations and genes in individual patients of rare genetic diseases.

The Undiagnosed Diseases Network International: Five years and more!

Undiagnosed rare diseases (URDs) account for a significant portion of the overall rare disease burden, depending upon the country. Hence, URDs represent an unmet medical need. A specific challenge posed by the ensemble of the URD patient cohort is the heterogeneity of its composition; the group, indeed, includes very rare, still unidentified conditions as well as clinical variants of recognized rare diseases. Exact disease recognition requires new approaches that cut across national and institutional boundaries, may need the implementation of methods new to diagnostics, and embrace clinical care and research. To address these issues, the Undiagnosed Diseases Network International (UDNI) was established in 2014, with the major aims of providing diagnoses to patients, implementing additional diagnostic tools, and fostering research on novel diseases, their mechanisms, and their pathways. The UDNI involves centres with internationally recognized expertise, and its scientific resources and know-how aim to fill the knowledge gaps that impede diagnosis, in particularly for ultra-rare diseases. Consequently, the UDNI fosters the translation of research into medical practice, aided by active patient involvement. The goals of the UDNI are to work collaboratively and at an international scale to: 1) provide diagnoses for individuals who have conditions that have eluded diagnosis by clinical experts; 2) gain insights into the etiology and pathogenesis of novel diseases; 3) contribute to standards of diagnosing unsolved patients; and 4) share the results of UDNI research in a timely manner and as broadly as possible.

Rare cancers of unknown etiology: lessons learned from a European multi-center case-control study.

Rare cancers together constitute one fourth of cancers. As some rare cancers are caused by occupational exposures, a systematic search for further associations might contribute to future prevention. We undertook a European, multi-center case-control study of occupational risks for cancers of small intestine, bone sarcoma, uveal melanoma, mycosis fungoides, thymus, male biliary tract and breast. Incident cases aged 35-69 years and sex-and age-matched population/colon cancer controls were interviewed, including a complete list of jobs. Associations between occupational exposure and cancer were assessed with unconditional logistic regression controlled for sex, age, country, and known confounders, and reported as odds ratios (OR) with 95% confidence intervals (CI). Interviewed were 1053 cases, 2062 population, and 1084 colon cancer controls. Male biliary tract cancer was associated with exposure to oils with polychlorinated biphenyls; OR 2.8 (95% CI 1.3-5.9); male breast cancer with exposure to trichloroethylene; OR 1.9 (95% CI 1.1-3.3); bone sarcoma with job as a carpenter/joiner; OR 4.3 (95% CI 1.7-10.5); and uveal melanoma with job as a welder/sheet metal worker; OR 1.95 (95% CI 1.08-3.52); and cook; OR 2.4 (95% CI 1.4-4.3). A confirmatory study of printers enhanced suspicion of 1,2-dichloropropane as a risk for biliary tract cancer. Results contributed to evidence for classification of welding and 1,2-dichloropronane as human carcinogens. However, despite efforts across nine countries, for some cancer sites only about 100 cases were interviewed. The Rare Cancer Study illustrated both the strengths and limitations of explorative studies for identification of etiological leads.

Carbon monoxide poisoning while scuba diving: a rare event?

Contamination of breathing gas is a risk for all divers. Some hydrocarbon contaminants will be sensed by the diver and the dive profile aborted. On the contrary, carbon monoxide may not be recognized by the diver and catastrophic consequences can result. Reported here is the fatal case of carbon monoxide poisoning while scuba diving, an event that has rarely been reported in the medical literature. A detailed review of other published cases of CO poisoning while scuba diving is included, attempting to identify causes in common and propose methods of prevention.

Successful use of hyperbaric oxygen therapy for limb salvage of acute limb ischemia as a complication of acute carbon monoxide poisoning.

Acute limb ischemia (ALI) as a complication of acute carbon monoxide (CO) poisoning is rare. Several reports have utilized hyperbaric oxygen therapy (HBO2) as an adjunctive therapy for peripheral arterial diseases. However, no study has yet described the use of HBO2 for ALI precipitated by CO poisoning. Herein we report successful limb salvage achieved with adjunctive HBO2 and conventional therapies in a patient with CO-induced ALI. A 69-year-old man was admitted with acute CO poisoning; ALI of both lower extremities occurred on hospitalization day 3. Pre-existing risk factors for ALI other than CO were not definite. After conventional treatments including catheter-directed thrombolysis and endovascular thrombectomy, the right-side lesion remained and a left-side lesion was newly developed. In addition to prior therapies, 47 sessions of serial HBO2 were administered as adjunctive therapy, resulting in limb salvage. Acute CO poisoning can cause ALI as a rare complication. HBO2 may be utilized as an adjunctive treatment in ALI.

Noncompletion and nonpublication of trials studying rare diseases: A cross-sectional analysis.

BACKGROUND: Rare diseases affect as many as 60 million people in the United States and Europe. However, most rare diseases lack effective therapies and are in critical need of clinical research. Our objective was to determine the frequency of noncompletion and nonpublication of trials studying rare diseases. METHODS AND FINDINGS: We conducted a cross-sectional analysis of randomized clinical trials studying rare diseases as defined by the Genetic and Rare Disease Information Center database that were registered in ClinicalTrials.gov between January 1, 2010, and December 31, 2012, and completed or discontinued by December 31, 2014. Our main outcome measures were the frequency of trial noncompletion and, among completed studies, frequency of trial nonpublication at 2 and 4 years following trial completion. Reasons for discontinuation were extracted from the registry, and trial sponsors were contacted for additional information, as needed. Two independent investigators performed publication searches for each trial in PubMed, EMBASE, and GoogleScholar, allowing for a minimum of 45 months between trial completion and publication. When a publication could not be identified, trial sponsors were contacted to confirm publication status. The impact of funding source on trial noncompletion was assessed with multivariable logistic regression, and the effect on time to publication was examined with Cox proportional hazards regression. Control variables included intervention type, trial phase, masking, enrollment, and study population. We analyzed 659 rare disease trials accounting for 70,305 enrolled patients. Industry was the primary funder for 327 trials (49.6%) and academic institutions for 184 trials (27.9%). There were 79 trials (12.0%) focused on pediatric populations. A total of 199 trials (30.2%) were discontinued. Lack of patient accrual (n = 64, 32.1%) and informative termination (n = 41, 20.6%) were the most common reasons for trial noncompletion. Among completed trials, 306 (66.5%) remained unpublished at 2 years and 142 (31.5%) at 4 years. In multivariable analyses, industry-funded trials were less likely to be discontinued than trials funded by healthcare centers (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.34-4.39, P = 0.003). We found no significant association between funding source and time to publication. A total of 18,148 patients were enrolled in trials that were discontinued or unpublished 4 years after completion. A potential limitation of our study is that certain interventional trials for rare diseases may not have been registered in ClinicalTrials.gov, in particular Phase 0 and Phase I trials, which are not required to be registered. CONCLUSIONS: In this study, over half of clinical trials initiated for rare diseases were either discontinued or not published 4 years after completion, resulting in large numbers of patients with rare diseases exposed to interventions that did not lead to informative findings. Concerted efforts are needed to ensure that participation of patients in rare disease trials advances scientific knowledge and treatments for rare diseases.

Molecular genetic characterization reveals linear tumor evolution in a pulmonary sarcomatoid carcinomas patient with a novel PHF20-NTRK1 fusion: a case report.

BACKGROUND: Pulmonary sarcomatoid carcinoma (SC) consists of both carcinomatous and sarcomatous tumors with high degree of malignancy, rapid progression, and poor prognosis. However, little is known regarding how pulmonary SC develops and progresses. CASE PRESENTATION: A 66-year-old male was initially diagnosed with stage IIIa lung cancer containing both adenocarcinoma (ADC) and SC. Adjuvant chemotherapy was administrated post-surgery, however, recurrence with SC only soon followed. Mutation profiling of the patient's microdissected ADC and SC components of the primary lesion and recurrent tumor was performed by targeted next-generation sequencing (NGS) of 416 cancer-relevant genes. Our data showed that primary SC/ADC and the recurrent SC shared multiple gene mutations including EGFR, NF1, TP53, CDKN2B, and SMARCA4, while both primary and recurrent SCs had a unique TP53 exon 4 splicing mutation frequently observed in sarcoma. Interestingly, a novel PHF20-NTRK1 fusion was acquired in the recurrent SC, which may be a potential driver for SC recurrence. CONCLUSIONS: The molecular genetic characteristics of tumor tissues at different stages reveals a linear tumor evolution model in this case, and support that the primary SC derived from the original lung ADC during the evolution of the tumor. We also identified a novel PHF20-NTRK1 fusion, which may contribute to the disease recurrence, and that can be potentially targeted with NTRK1 inhibitors for treatment.

Reported environmental exposures are inversely associated with obtaining a genetic diagnosis in the Undiagnosed Diseases Network.

The Undiagnosed Diseases Network (UDN) aims to achieve a unifying etiologic diagnosis for patients with mysterious conditions. Although the UDN has focused on the identification of genetic determinants, environmental etiologies may be causative or modifying agents that interact with predisposing genes. We developed and implemented a screening questionnaire to assess environmental exposures in UDN patients. We hypothesized that patients with potentially adverse environmental exposures would be less likely to have a genetic basis for their undiagnosed disease. Among seven postnatal environmental exposure categories assessed in 269 UDN participants, patients with a confirmed or strong candidate genetic diagnosis were significantly less likely to report exposures to metals, dust, or chemicals (p < 0.05). A composite variable of the seven exposure categories was substantially more common (40%) in patients without a genetic diagnosis than in those with a genetic diagnosis (18.4%) (p = 0.004). In multivariable analysis adjusting for age and sex, the composite variable of any positive environmental exposure was associated with a reduced odds of finding a genetic diagnosis (OR 0.41, 95% CI 0.18-0.96, p = 0.04). These results were generally robust to exclusion of patients with early life disease onset. Our results suggest a possible approach to increase the yield of genetic etiologies for adult undiagnosed diseases by first focusing on patients without significant environmental exposures. Still, there is ample reason to expect cases in which specific environmental exposures impact the risk of clinically evident genetic disease. Our findings emphasize the importance of systematic investigations of potential environmental risk factors for undiagnosed diseases.

Mediation analysis for common binary outcomes.

Mediation analysis provides an attractive causal inference framework to decompose the total effect of an exposure on an outcome into natural direct effects and natural indirect effects acting through a mediator. For binary outcomes, mediation analysis methods have been developed using logistic regression when the binary outcome is rare. These methods will not hold in practice when a disease is common. In this paper, we develop mediation analysis methods that relax the rare disease assumption when using logistic regression. We calculate the natural direct and indirect effects for common diseases by exploiting the relationship between logit and probit models. Specifically, we derive closed-form expressions for the natural direct and indirect effects on the odds ratio scale. Mediation models for both continuous and binary mediators are considered. We demonstrate through simulation that the proposed method performs well for common binary outcomes. We apply the proposed methods to analyze the Normative Aging Study to identify DNA methylation sites that are mediators of smoking behavior on the outcome of obstructed airway function.

Triggers, clinical manifestations, and management of pediatric erythema multiforme: A systematic review.

BACKGROUND: Erythema multiforme (EM) is an acute inflammatory mucocutaneous condition. EM is rarely described in children and infants. OBJECTIVE: To investigate the triggers, clinical manifestations, and treatment of pediatric EM. METHODS: Systematic literature review of pediatric EM. RESULTS: After full-text article review, we included 113 articles, representing 580 patients. The mean age was 5.6 years, ranging 0.1-17 years. Infectious agents were the main triggers: herpes simplex virus (HSV) in 104 patients (17.9%) and Mycoplasma pneumoniae in 91 patients (15.7%). In total, 140 cases (24.1%) were drug-related and 89 cases (15.3%) had other triggers, such as vaccines (19 patients, 3.2%). In total, 229 patients had EM major (39.5%). Treatment was supportive care only (180 patients, 31.1%), systemic corticosteroids (115 patients, 19.8%), antivirals (85 patients, 14.6%), and antibiotics (66 patients, 11.3%), mostly macrolides (45 patients, 7.7%). Long-term sequelae were rare (1.3%). Pediatric EM was reported in 19 infants (3.2%). The main trigger was vaccination (9 patients). Infantile EM was EM major in 2 cases and EM minor in 17. Infants were less prone to develop EM major than older children (P < .01). Pediatric EM was recurrent in 83 cases (14.3%), which was triggered by HSV in 36 patients (61%). Recurrence affected older children. LIMITATIONS: Potential confusion between Steven Johnson syndrome and EM major in addition to publication bias. CONCLUSION: Pediatric EM is a rare disease, mainly triggered by infections. This condition can affect all mucosal surfaces, most commonly the oral mucosae. The diagnosis is clinical, and management relies on supportive care. Vaccines are a particular trigger in infants. Recurrent cases are most commonly linked to HSV. Dermatologists and pediatricians should be aware of this potentially recurrent and severe condition.

Identifying risk groups of infectious spondylitis in patients with end-stage renal disease under hemodialysis: a propensity score-matched case-control study.

BACKGROUND: Patients with end-stage renal disease (ESRD) under hemodialysis (HD) are at greater risks of infectious spondylitis (IS), but there is no reliable predictor that facilitate early detection of this relatively rare and insidious disease. METHODS: A retrospective review of the medical records from patients with ESRD under HD over a 12-year period was performed at a tertiary teaching hospital, and those with a first-time diagnosis of IS were identified. A 1:4 propensity score-matched case-control study was carried out, and baseline characteristics, underlying diseases, and laboratory data were compared between the study group and the control group, one month before the date of diagnosis or the index date respectively. RESULTS: A total of 16 patients with IS were compared with 64 controls. After adjustment, recent access operation (odds ratio [OR], 13.27; 95% confidence interval [CI], 3.53 to 49.91; p <  0.001), degenerative spinal disease (OR, 12.87; 95% CI, 1.89 to 87.41; p = 0.009), HD through a tunneled cuffed catheter (OR, 6.75; 95% CI, 1.74 to 26.14; p = 0.006), low serum levels of hemoglobin, albumin, as well as high levels of red blood cell volume distribution width (RDW), alkaline phosphatase (ALP), and high sensitivity C-reactive protein were significant predictors for a IS diagnosis one month later. Receiver operating characteristic curves for hemoglobin, RDW, ALP, and albumin all showed good discrimination. The further multivariate models identified both high serum ALP levels and low serum RDW levels following a recent access intervention in patients with relatively short HD vintages may be indicative of the development of IS. CONCLUSION: Patients under HD with relatively short HD vintages showing either elevated ALP levels or low RDW levels following a recent access intervention should prompt clinical awareness about IS for timely diagnosis.

The Human Phenotype Ontology in 2017.

Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

Traumatic ulcerative granuloma with stromal eosinophilia - clinical case report, literature review, and differential diagnosis.

BACKGROUND: Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is a rare self-limiting condition of the oral mucosa. The lesion manifests as an isolated ulcer that can be either asymptomatic or associated with mild to severe pain, and in most cases, it affects the tongue. TUGSE lesions may mimic malignancy such as squamous cell carcinoma, CD30 positive lymphoproliferative disorder, or infectious diseases such as primary syphilis, tuberculosis, or Epstein-Barr virus mucocutaneous ulcer. Histologically dominating cells are lymphocytes, histiocytes, and eosinophils. CASE PRESENTATION: We describe a TUGSE case of a patient with a solitary ulcer on the lower left retromolar buccal plane. Upon presentation, the patient reported a swelling on the buccal mucosa of the left lower jaw since 1 year with rapid growth over the last days and mild pain while chewing. The diameter of the intraoral lesion on the lower left retromolar buccal plane was approximately 4 × 3 cm; the lesion presented as indurated base with a central superficial ulceration of 2 × 1 cm, indicative for a malignant process. Histologically, the ulceration showed an expanding, infiltrative, and vaguely granulomatous morphology, involving the superficial mucosa and the fatty tissue, and extended between the deep striated muscle fibers. The lesion was rich in lymphocytes, histiocytes, and eosionophils intermingled with activated T-blasts without phenotypic abnormalities. TUGSE was then diagnosed based on the phenotype (especially the lacking expression of CD30, the retained T-cell phenotype, and the absence of Epstein-Barr virus), the clinical presentation, and the morphology. Twenty-six months after diagnosis, no recurrence of the ulceration was seen. CONCLUSIONS: As TUGSE may mimic malignancy or infectious diseases, biopsy is mandatory and should be combined with thorough clinical examination. A screening for infectious diseases (mainly syphilis, Epstein-Barr virus, and HIV infections) must be performed routinely. In most cases, the lesions resolve spontaneously, obviating the need of further actions other than clinical follow-up. The pathogenesis of TUGSE lesions is still under debate, although local traumatic events and a locotypic immune response have been suggested to be major contributing factors.

Secretan's syndrome: case report.

Secretan's syndrome is a rare clinical condition with recurrent swelling of the forearm and dorsum of the hand, together with flexion contracture of the fingers and a thumb that is spared. The disease is associated with automutilation. We present a typical case of a 42-year old women with Secretan's syndrome.