Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by painful, necrotic ulceration. It typically affects patients in the third to sixth decades of life, with almost equal incidence in men and women. PG occurs most frequently on the lower extremities. Five clinical variants are currently recognized: classic, bullous, pustular, vegetative, and peristomal types. Half of PG cases are seen in association with systemic disease. Mimickers include infection, vascular insufficiency ulcers, systemic vasculitides, autoimmune disease, cancer, and exogenous tissue injury, among others. PG is often a diagnosis of exclusion, as there are no specific laboratory or histopathologic findings to confirm the diagnosis. PG thus presents many clinical challenges: it is difficult to diagnose, is frequently misdiagnosed, and often requires a work-up for underlying systemic disease. Successful management of PG typically requires multiple modalities to reduce inflammation and optimize wound healing, in addition to treatment of any underlying diseases. Prednisone and cyclosporine have been mainstays of systemic treatment for PG, although increasing evidence supports the use of biologic therapies, such as tumor necrosis factor-a inhibitors, for refractory cases of PG. Here, we review the clinical presentation and pathophysiology of PG, as well as its associated conditions, diagnostic work-up, and management.

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Etiology and management of pyoderma gangrenosum: a comprehensive review.

自身免疫性垂体炎是一种罕见的内分泌疾病,多发生于妊娠或产后.其发病机制不明,临床表现多变,主要包括垂体压迫、腺垂体功能减退症、尿崩症和高催乳素血症等相关症状.治疗目的主要是减小垂体肿块的大小和(或)替代有缺陷的内分泌功能.多数患者需要长期使用激素替代治疗。

Autoimmune hypophysitis

The standard diagnostic approach of suspected deep vein thrombosis (DVT) is serial lower limb compression ultrasound (CUS) of proximal veins. Although it only assesses the proximal veins, withholding anticoagulant treatment in patients with a negative CUS on day one and after one week has been proven to be safe. However, in many centres, distal DVT is systematically screened for and treated by anticoagulants. The objectives of the review were 1) to evaluate the rate of extension of distal DVTs to proximal veins 2) to compare the safety of proximal limited CUS versus single complete CUS. We performed a MEDLINE search covering the period from January 1983 to January 2005 by using the key-words "calf vein thrombosis", "distal thrombosis" and "compression ultrasonography". English, German and French language original studies were retrieved. Moreover, references of retrieved articles were screened in order to detect missed pertinent articles. We pooled data of management studies where proximal or complete (i.e. proximal and distal) CUS were used, respectively. Studies evaluating CUS limited to the proximal veins showed a good safety profile with a pooled estimate of the 3-month thromboembolic rate of 0.6% (95% CI: 0.4-0.9%) in patients in whom anticoagulation was withheld. Studies using proximal and distal CUS showed a similar pooled estimate of the 3-month thromboembolic rate (0.4%, 95% CI: 0.1-0.6%) but distal DVT accounted for as many as 50% of all diagnosed DVTs in those series. Therefore, searching for distal DVT potentially doubles the number of patients given anticoagulant therapy and entails a risk of over-treatment. Data suggesting that anticoagulation is indicated for distal DVT are limited, and realizing distal CUS entails a risk of over-treatment. There is an urgent need for randomised trials assessing the usefulness of anticoagulant treatment in distal DVT.

Clinical relevance of distal deep vein thrombosis. Review of literature data.

Context In patients with suspected lower extremity deep vein thrombosis (DVT), compression ultrasound (CUS) is typically the initial test to confirm or exclude DVT. Patients with an initial negative CUS result often require repeat CUS after 5 to 7 days. Whole-leg CUS may exclude proximal and distal DVT in a single evaluation. Objective To determine the risk of venous thromboembolism after withholding anticoagulation in patients with suspected lower extremity DVT following a single negative whole-leg CUS result. Data Sources MEDLINE, EMBASE, CINAHL, LILACS, Cochrane, and Health Technology Assessments databases were searched for articles published from January 1970 through November 2009. Supplemental searches were performed of Internet resources, reference lists, and by contacting content experts. Study Selection Included studies were randomized controlled trials and prospective cohort studies of patients with suspected DVT and a negative whole-leg CUS result who did not receive anticoagulant therapy, and were followed up at least 90 days for venous thromboembolism events. Data Extraction Two authors independently reviewed and extracted data regarding a single positive or negative whole-leg CUS result, occurrence of venous thromboembolism during follow-up, and study quality. Results Seven studies were included totaling 4731 patients with negative whole-leg CUS examinations who did not receive anticoagulation. Of these, up to 647 patients (13.7%) had active cancer and up to 725 patients (15.3%) recently underwent a major surgery. Most participants were identified from an ambulatory setting. Venous thromboembolism or suspected venous thromboembolism–related death occurred in 34 patients (0.7%), including 11 patients with distal DVT (32.4%); 7 patients with proximal DVT (20.6%); 7 patients with nonfatal pulmonary emboli (20.6%); and 9 patients (26.5%) who died, possibly related to venous thromboembolism. Using a random-effects model with inverse variance weighting, the combined venous thromboembolism event rate at 3 months was 0.57% (95% confidence interval, 0.25%-0.89%). Conclusion Withholding anticoagulation following a single negative whole-leg CUS result was associated with a low risk of venous thromboembolism during 3-month follow-up.

https://jamanetwork.com/journals/jama/articlepdf/185295/jcr90007_438_445.pdf

Risk of Deep Vein Thrombosis Following a Single Negative Whole-Leg Compression Ultrasound: A Systematic Review and Meta-analysis

PURPOSE: To establish the safety of withholding anticoagulation therapy after negative findings at a complete lower limb ultrasonographic (US) examination of the symptomatic leg for suspected deep venous thrombosis (DVT). MATERIALS AND METHODS: Regional ethics committee approval and patient consent were obtained. A total of 542 consecutive ambulatory patients presented to the emergency department and were prospectively recruited from April 2001 to May 2003. Of these patients, 16 were excluded, and radiology residents and sonographers performed a complete lower limb US examination by means of compression and Doppler US in 526 patients. Patients with negative US findings received no anticoagulation therapy, and they were observed for occurrence of any thromboembolic event for 3 months. Patients with progressive or new symptoms that were indicative of thromboembolism within the follow-up period underwent objective testing with US, computed tomographic (CT) pulmonary angiography, or both. RESULTS: There were ...

Deep venous thrombosis: withholding anticoagulation therapy after negative complete lower limb US findings.

Individuals presenting with primary hyperparathyroidism (PHPT) at a young age commonly have an underlying germline gene mutation in one of the following genes: MEN1, CASR, or CDC73. A small number of families with primary hyperparathyroidism have been identified with germline mutations in CDKN1B and those patients with primary hyperparathyroidism have almost exclusively been women who present in middle age suggesting that the age of onset of PHPT in MEN4 may be later than that of MEN1. We present a case of apparently sporadic PHPT presenting in adolescence with single gland disease associated with a novel CDKN1B germline mutation (heterozygote for a missense mutation in exon 1 of the CDKN1B gene (c.378G>C) (p.E126D)). The implication from this case is that CDKN1B germline mutations may be associated with PHPT at an earlier age than previously thought.

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Early Onset Primary Hyperparathyroidism Associated with a Novel Germline Mutation in CDKN1B

Cushing's syndrome (CS) due to ectopic adrenocorticotrophic hormone (ACTH) is associated with a variety of tumours most of which arise in the thorax or abdomen. Prostate carcinoma is a rare but important cause of rapidly progressive CS. To report a case of severe CS due to ACTH production from prostate neuroendocrine carcinoma and summarise previous published cases. A 71-year-old male presented with profound hypokalaemia, oedema and new onset hypertension. The patient reported two weeks of weight gain, muscle weakness, labile mood and insomnia. CS due to ectopic ACTH production was confirmed with failure to suppress cortisol levels following low- and high-dose dexamethasone suppression tests in the presence of a markedly elevated ACTH and a normal pituitary MRI. Computed tomography demonstrated an enlarged prostate with features of malignancy, confirmed by MRI. Subsequent prostatic biopsy confirmed neuroendocrine carcinoma of small cell type and conventional adenocarcinoma of the prostate. Adrenal steroidogenesis blockade was commenced using ketoconazole and metyrapone. Complete biochemical control of CS and evidence of disease regression on imaging occurred after four cycles of chemotherapy with carboplatin and etoposide. By the sixth cycle, the patient demonstrated radiological progression followed by recurrence of CS and died nine months after initial presentation. Prostate neuroendocrine carcinoma is a rare cause of CS that can be rapidly fatal, and early aggressive treatment of the CS is important. In CS where the cause of EAS is unable to be identified, a pelvic source should be considered and imaging of the pelvis carefully reviewed.

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Severe Cushing's syndrome due to small cell prostate carcinoma: a case and review of literature.

Objective Lymphocytic hypophysitis (LH) is a rare chronic inflammatory disorder characterized by lymphocytic infiltration of the pituitary gland commonly affecting women during pregnancy or post-partum period. The pathogenesis remains uncertain, however an autoimmune process is frequently implicated. There is limited data on the occurrence of LH outside the setting of autoimmunity. Case We describe a 37-year-old man presenting with diarrhoea, nausea, weight loss, low-grade fever, headache and cerebrospinal fluid analysis consistent with aseptic meningitis. Magnetic resonance imaging (MRI) demonstrated a homogenously enlarged pituitary gland with biochemical testing revealing partial hypopituitarism with adenocorticotrophic hormone and gonadotrophin deficiency. Notably, his free thyroid hormone levels were elevated with a suppressed thyroid-stimulating hormone and a suppressed thyroid technetium scan consistent with thyroiditis. Tissue antibodies including thyroid antibodies were negative. Following introduction of hydrocortisone, he developed transient diabetes insipidus which spontaneously resolved after 4 months. Thyrotoxicosis resolved after 5 weeks and thyroxine was commenced as he developed secondary hypothyroidism. Repeat MRI 3 months later showed a reduction in the size of the pituitary gland which by 6 months had returned to normal size. He remains well on hydrocortisone, thyroxine and testosterone replacement. Conclusions Based on clinical and radiological grounds, the diagnosis was consistent with lymphocytic hypophysitis associated with subacute thyroiditis. This is only the second report of this combination in the absence of autoimmunity and the first report of LH and thyroiditis with associated aseptic meningitis in the absence of tissue autoantibodies. We propose a possible viral illness as the unifying aetiological cause

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Lymphocytic hypophysitis with associated thyroiditis in a man with aseptic meningitis

Background Pyoderma gangrenosum (PG) is a rare inflammatory skin condition, characterized by progressive and recurrent skin ulceration, often representing a pathergy response. Observations We report a case of spontaneous retrosternal PG that developed on the background of previous PG of the skin of the back. The patient had underlying ulcerative colitis. After failure of prednisone, minocycline, and dapsone, a novel method was instituted. Local flushing with dexamethasone, by a radiologically inserted retrosternal catheter with precordial suction, induced a rapid and sustained response. Subsequently maxillary sinus PG developed after the patient's tooth extraction. This responded to local corticosteroid injections in combination with systemic corticosteroid. Limitations Further reports of this technique are required to consolidate its use and infusion variables. Conclusions Two unusual sites of PG have been described, with successful treatment by a novel local steroid infusion. The profound sensitivity to trauma is demonstrated, which suggests that prophylactic corticosteroid may be useful for essential surgical intervention.

Michael J. Swarbrick

Papers

Deep venous thrombosis: withholding anticoagulation therapy after negative complete lower limb US findings.

Early Onset Primary Hyperparathyroidism Associated with a Novel Germline Mutation in CDKN1B

Severe Cushing's syndrome due to small cell prostate carcinoma: a case and review of literature.

Lymphocytic hypophysitis with associated thyroiditis in a man with aseptic meningitis

Cavitary pyoderma gangrenosum treated with local infusion of corticosteroid.