Dupuytren’s contracture is an abnormal thickening of the fibrous tissue under the skin in the hand that causes flexion of the fingers. The idiopathic condition is more common in men and strongly associated with a family history. Dupuytrens’s generally starts as a firm lump or pit in the palm as patients complain of difficulty placing the hand flat on a surface. The lump then progresses causing tissue under the skin to form bands and contract. The fingers then begin to bend (most commonly the 4th and 5th digits) and can no longer fully extend. This progressive finger flexion makes it difficult for patients to do certain things like wear gloves, put the hand in pocket, and hygiene.

The first line treatment of Dupuytren’s is observation as the contracture may be non-progressive. Splinting and physical therapy are not effective for initial treatment, although therapy may be used after injections or surgical treatment. Collagenase clostridium (Xiaflex) is an injectable enzyme that causes the collagen to degrade within connective tissue which helps release the contracture. Xialfex is injected into the contracture and the patient is instructed to return to the office in 24-72 hours for passive extension manipulation of the involved fingers under local anesthesia. After the manipulation has been performed in the office the patient is often sent to physical therapy to be fitted for an extension night splint and to work on finger extension. The extension splint is typically worn at night for 4 weeks. The patient may have Xiaflex repeated at 6 weeks from the initial injection should a flexion contracture remain. Surgical treatments such as resection or fasciectomy are generally used when nonoperative treatments fail or when the flexion contracture progresses.

References

1. Black EM, Blazar PE. Dupuytren Disease: An Evolving Understanding of an Age Old Disease. JAAOS 2011; 19: 746-757.

2. Dupuytren’s Disease. http://www.orthobullets.com. Accessed on 2/18/2017.

Answer is D. The patient in the clinical vignette above is presenting with an NSTEMI. The TIMI Score (aka. Thrombolysis in Myocardial Infarction Score) is used to estimate the risk of death, MI or need for urgent cardiac catheterization in patients presenting with unstable angina or NSTEMI.4 It will risk stratify patients to low risk, intermediate risk, or high risk based on the number of risk factors a patient is positive for. There are 7 components, with each risk factor worth one point for a maximum score of 7.4 Typically, the higher the score, the more likely one of the above events will occur. The criteria includes:
Age ≥ 65
Aspirin use in the past 7 days
Severe angina (≥2 episodes within 24 hrs)
Positive cardiac biomarkers
≥3 risk factors for coronary artery disease (HTN, hypercholesterolemia, family hx of CAD, DM, smoking)
Previous history of coronary artery disease (stenosis of ≥ 50% stenosis)
ST changes ≥0.5mm on EKG

The scoring system is also used to determine whether a patient should be managed conservatively with drug therapy or with more invasive therapy such as early coronary angiography and revascularization. Low risk patients (score of 0-2) are typically followed with drug therapy. Intermediate patients (score of 3-4) and high risk patients (score of 5-7) are typically followed with a regimen consisting of multiple drugs and early coronary intervention. Our patient above has a TIMI Score of 5 (1 point for his age, 1 point for aspirin use within 7 days, 1 point for positive cardiac biomarkers, 1 point for having ≥ 3 risk factors for CAD, and 1 point for ST changes ≥0.5mm on EKG). Thus, he would be managed with a more invasive regimen, such as a cardiac catheterization. (A)Well’s Criteria is used for risk of DVT/PE. (B)Ranson’s Criteria is used to determine the prognosis and severity of patients with pancreatitis. (C)CHADS VASc Score is utilized for the risk of stroke in patients with atrial fibrillation. (E)CURB 65 is used to determine the risk of death in patients with community acquired pneumonia. The above patient does not present with a chief complaint that would require the utilization of these other scoring systems.

References:
1. Abbott JD, Oettgen P, eds. Acute Coronary Syndromes. DynaMed. http://web.a.ebscohost.com.ezproxymcp.flo.org/dynamed/detail?sid=7b9cfc99-5e55-46f9-a275-4bbe5f0afe0e%40sessionmgr4006&vid=0&hid=4104&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3d#AN=116779&db=dme. Published October 27, 2016. Accessed February 4, 2017.

2. NSTEMI vs. STEMI. NSTEMI.org. http://nstemi.org/nstemi-vs-stemi/. Published January 12, 2017. Accessed February 4, 2017.

3. Papadakis MA, McPhee SJ, Rabow MW. Current Medical Diagnosis & Treatment 2015. 54th ed. McGraw-Hill Education; 2014.

4. TIMI Risk Score for UA/NSTEMI Mnemonic. Internalize Medicine. http://www.internalizemedicine.com/2012/08/timi-risk-score-for-uanstemi-mnemonic.html. Published August 11, 2012. Accessed February 4, 2017.

5. Wilson PW, Douglas PS. Epidemiology of Coronary Heart Disease. UpToDate. http://www.uptodate.com/contents/epidemiology-of-coronary-heart-disease. Published January 23, 2015. Accessed February 4, 2017.

Answer: (C) Mitral regurgitation is a common valvular disorder that results in the backflow of blood from the left ventricle to the left atrium due to incomplete closure of the mitral valve. It results from an abnormality of the mitral valve apparatus, ischemia, or enlargement of the LV with systolic dysfunction. A common cause of mitral regurgitation is dilated cardiomyopathy, which is classified by enlargement of the LV, LA, and sometimes the RA and RV if it becomes severe enough. The patient in this example has a PMH of dilated cardiomyopathy, though she has been asymptomatic in the past. Patients can be asymptomatic, or they can exhibit signs of HF (e.g. LE edema, DOE, fatigue, etc.) as it becomes more chronic. A blowing holosystolic murmur at the apex radiating to the left axilla is classic for MR. The EKG reveals atrial fibrillation, which is a common complication due to years of left atrial enlargement.

(A) Mitral valve prolapse is a valve disorder most common in women, and in patients with connective tissue disorders (e.g. Marfan’s syndrome/Ehlers-Danlos syndrome) or hypertrophic cardiomyopathy, not dilated cardiomyopathy. It results from mitral valve leaflets entering the left atrium during systole. It often presents with heart palpitations or syncope and is associated with a mid-systolic click heard at the apex, without radiation. It can progress to symptomatic mitral regurgitation, with pulmonary edema and signs of heart failure. (B) Tricuspid regurgitation results from incomplete closure of the tricuspid valve and consequently, backflow of blood from the RV to the RA. It can be a severe complication of chronic MR. It commonly results from left-sided HF that progresses to RV dilation and right-sided HF. However, the classic murmur of tricuspid regurgitation is a holosystolic murmur at the lower left sternal border (not the apex) without radiation. Although (D) CHF is the current clinical picture, the most likely cause of the patient’s clinical presentation is mitral regurgitation. The clinical picture is of decompensated MR, which manifests as heart failure. Even though the CXR reveals interstitial and alveolar edema with bilateral pleural effusions which is indicative of HF, the physical exam reveals the murmur characteristic of MR as well as atrial fibrillation on the EKG. Therefore, although the patient is presenting with CHF, the most likely cause of the CHF is MR.

Reference: Otto CM. Clinical manifestations and diagnosis of chronic mitral regurgitation. UpToDate. http://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-chronic-mitral-regurgitation. Updated January 29, 2016. Accessed January 31, 2017.

Correct: The correct answer is D: Coreg (carvedilol), Prinivil (Lisinopril). Only 3 beta blockers have been approved by the FDA for the treatment of heart failure patients which have shown to reduce mortality. They are carvedilol, metoprolol, and bisoprolol. Guidelines say the highest level of evidence to reduce mortality in a patient with reduced ejection fraction is to start them on a recommended beta blocker plus an ACE-I such as Lisinopril2. This is why answer choice (D) is correct.

Incorrect: The answer choice (A) Veletri (epoprostenol), Aldactone (spironolactone) is incorrect because Epoprostenol is a drug that is used to treat pulmonary arterial hypertension. Epoprostenol is contraindicated in patient with left ventricular heart failure. The answer choice (B) Inderal XL (propranolol), Epaned (enalapril) is incorrect because though an ACE-I is the proper treatment for HF, Propanol is not one of the 3 beta blockers that is used in treatment of HF2. The answer choice (C) Nitrostat (nitroglycerin) is generally used for angina and Eliquis (apixaban) is incorrect because it is used for irregular heart rhythms such as atrial fibrillation to prevent blood clots.

References
1. Su V, Chang Y, Hu Y et al. Carvedilol, Bisoprolol, and Metoprolol Use in Patients With Coexistent Heart Failure and Chronic Obstructive Pulmonary Disease. Medicine. 2016;95(5):e2427. doi:10.1097/md.0000000000002427.
2. Gheorghiade M. beta-Blockers in Chronic Heart Failure. Circulation. 2003;107(12):1570-1575. doi:10.1161/01.cir.0000065187.80707.18.
3. Mozaffarian D, Benjamin E, Go A et al. Heart Disease and Stroke Statistics—2016 Update. Circulation. 2015;133(4):e38-e360. doi:10.1161/cir.0000000000000350.
4. Kannel WBelanger A. Epidemiology of heart failure. American Heart Journal. 1991;121(3):951-957. doi:10.1016/0002-8703(91)90225-7.

The correct answer is C. Schatzki/esophageal ring. Esophageal ring is the correct diagnosis based on the patient’s presentation and lack of physical exam findings. The patient has intermittent dysphagia to solid foods only and exhibits “steakhouse syndrome” as she has the most dysphagia when eating steak and bread with others.4 The patient has uncontrolled heartburn and reflux, which has been linked to the development of Schatzki rings. An esophageal motility disorder would be incorrect in this scenario because the patient does not have dysphagia to liquids. With motility disorders, the patient will have difficulty swallowing both liquid and solid foods. Candidiasis is possible in individuals who take inhaled steroids and can cause dysphagia and chest discomfort. Despite this, Candida esophagitis is not correct in this scenario. The patient had no evidence of candidiasis on physical exam. There were no fluffy white patches in her mouth or oropharynx.4 Lastly, GERD is not the correct answer. The patient exhibits symptoms of GERD, but it is unlikely that it is the primary reason for the patient’s dysphagia. GERD has been linked to the development of esophageal strictures, but in this case it would not be the most correct diagnosis.

References
1.Kafrouni M. Schatzki’s Ring. Memorial Hermann. http://www.memorialhermann.org/digestive/schatzkis-ring/. Published July 8, 2015. Accessed February 6, 2017.
2.Liu JJ, Kahrilas PJ. Pharyngeal and esophageal diverticula, rings, and webs. GI Motility Online. May 2006. doi:10.1038/gimo41.
3.Lundell L. Reflux esophagitis and peptic strictures. GI Motility Online. May 2006. doi:10.1038/gimo43.
4.Schatzki Ring. Schatzki Ring: Background, Pathophysiology, Epidemiology. http://emedicine.medscape.com/article/182647-overview. Accessed February 1, 2017.
5.Smith MS. Diagnosis and Management of Esophageal Rings and Webs. Gastroenterology & Hepatology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033540/. Published November 2010. Accessed February 5, 2017.

The answer is B. Exogenous ochronosis is a hyperpigmentation condition caused my chronic use of a variety of topical products. One of the most common offending agents is hydroquinone 2% cream, which the patient has used for about a year. The lesion is not symptomatic and presents as a worsening gray-black macule. A drug eruption can be a possibility due to the patients medication list. However, the presentation is not consistent with that of a morbiliform drug eruption. The onset of the lesion cannot be linked to the start of any of her medication and no blisters, erythema, angioedema, pruritus, necrosis or purpura is present. Melasma is a hypermelanosis of widely sun-exposed skin. The condition presents as hyper-pigmented macules, which are tan-brown rather than gray-black. Melasma also tends to be symmetrical and has a correlation with estrogen activity such as pregnancy and oral contraceptive pills. Because the patient has not had any recent hormonal changes, it is unlikely that she has Melasma. Post inflammatory hyperpigmentation (PIH) is a temporary pigmentation disorder that is caused by prior trauma, inflammatory skin conditions such as dermatitis, infections or certain medications. Melanocytes are increased due to inflammation of the epidermis and are transferred to the surrounding keratinocytes, resulting in hyperpigmentation (Ngan, 2015). The lesions are tan-brown or black in color and can become more prominent with sun exposure. It is unlikely that the patient has PIH due to the fact that she does not have a history of any inflammatory skin conditions in the area of the lesions, or is not taking a medication that is known to cause PIH.

References
Burkhart, C. G. (2015, August 19). Ochronosis Treatment & Management. Retrieved February 05, 2017, from http://emedicine.medscape.com/article/1104184-treatment#d6

Dyall-Smith, D. (2016, January). DermNet New Zealand. Retrieved February 05, 2017, from https://www.dermnetnz.org/topics/morbilliform-drug-reaction

Gandhi, V., Verma, P., & Naik, G. (2012). Exogenous ochronosis After Prolonged Use of Topical Hydroquinone (2%) in a 50-Year-Old Indian Female. Indian Journal of Dermatology, 57(5), 394–395. http://doi.org/10.4103/0019-5154.100498

Cervical myelopathy is a compressive injury to the spinal cord that most commonly occurs due to degenerative spondylosis in patients over 50 years of age. With aging the cervical discs desiccate and lose their height, the ligamentum flavum hypertrophies, osteophytes form, and the posterior longitudinal ligament may ossify. This degenerative cascade leads to compression of the cord. Symptoms can vary considerably and usually don’t follow a dermatomal pattern like cervical radiculopathy. Subtle changes in gait and balance are often the first signs of early myelopathy. Complaints of neck pain, loss of fine motor control of the upper extremity or “clumsy hands”, and paresthesia’s are common. Patients will often complain of increasing difficulty with hand writing over a few weeks to months. The proximal motor groups of the legs are more commonly affected than the distal motor groups in cervical myelopathy (which is opposite to the findings of lumbar stenosis). Changes is bowel and bladder function are rarely found with cervical myelopathy.

Several physical exam tests of the hands exist to screen for cervical myelopathy. For the finger escape sign, the patient is asked to extend and adduct the fingers. If the small and ring fingers flex and abduct after 30-60 seconds then cervical myelopathy is considered. Slow or clumsy hands may be evident by asking the patient to continuously make a fist and release 20 times in 10 seconds. Other upper motor neuron signs often present in patients with moderate to severe cervical myelopathy include hyperreflexia, a positive Hoffman’s sign, sustained clonus, and a positive Babanski’s. A Hoffman’s sign involves snapping the distal tip of the patient’s extended middle finger which leads to spontaneous flexion of the other fingers in patients with cervical myelopathy.

References
1. Sanford EM. Cervical Spondylotic Myelopathy: Diagnosis and Treatment. JAAOS 2001; 9: 376-388.
2. Rao R. Neck pain, Cervical Radiculopathy, and Cervical Myelopathy: Pathophysiology, Natural History, and Clinical Evaluation. AAOS Instruction Course Lecture. JBJS 2012. 84. 1871-1881.

Factor V Leiden Thrombophilia poses an increased risk of abnormal clot formation to diagnosed patients, especially younger individuals and of European ancestry. An inherited mutation of the F5 gene is present. This mutation prevents argon plasma coagulation (APC) in the coagulation pathway from inactivating Factor V which allows more time for clot formation and bigger, abnormal clots to occur. Risk of clot formation increases with 1 copy of the mutation but is even greater with 2 copies present.

A major risk factor for this condition and predisposes one to genetic diagnostic testing is having a close family member diagnosed with this disorder. Other risk factors include pregnancy, obesity, smoking, recent travel (especially on airplane), oral contraceptive pills, and hormone replacement therapy. Symptoms for this disorder include recurrent PE or DVT, occurrence of either at a young age, loss of pregnancy in the second or third trimester that is unexplained, or venous thrombosis in an unusual organ.

Choice B is the correct answer to the question given. Factor V Leiden Thrombophilia is not a benign condition as it increases the risk of abnormal clot formation. Given the patients’ previous DVT diagnosis and current pregnancy, clinical observation and risk factor counseling would not be appropriate as sole therapy. The patient should receive treatment with anticoagulant for the duration of the pregnancy to decrease risk of abnormal clot formation. She should not be given just prophylaxis as she did have a previous DVT and is currently pregnant which is a risk factor.

Discussion: Factor V Leiden Thrombophilia
Etiology: Factor V Leiden Thrombophilia is an inherited condition in which a gene mutation is present that leads to a state of increased risk of clot formation. It is the most common inherited disorder that causes a hypercoagulable state. For this reason, the initial MD in the case described above took extra precautions in terms of directing the workup the patient received.
Epidemiology: This mutation is more common in individuals of European ancestry. Individuals with 2 copies of the F5 mutation have an increased chance of up to 80 in 1,000 people developing abnormal clot formation3. Individuals with 1 copy of the F5 mutation have a 4-8 in 1,000 increased chance of abnormal clot formation. Normal risk for elevated clot formation is 1 in 1,000 individuals per year.

Pathophysiology: Factor V protein is produced primarily in the liver from instructions provided by the F5 gene. Until the coagulation pathway is stimulated by a blood vessel injury, factor V protein rotates in the bloodstream in its inactive form. Factor V plays an important role in the coagulation pathway. It is activated by factor X2. Once triggered, Factor V works as the activator of prothrombin which converts to thrombin when stimulated. Thrombin then activates fibrinogen which becomes the clot forming material known as fibrin2. Another role of factor V in the coagulation system is being inactivated by activated protein C (APC) which stops clots from becoming too big. In the condition of Factor V Leiden Thrombophilia, a genetic mutation of the F5 gene is present and causes the hypercoagulability as Factor V can no longer be inactivated by APC3. Thus, clots more time to form and can become bigger leading to abnormalities. Individuals with 2 copies of the inherited mutation (one from father and one from mother) have the greatest risk of increased clot formation.

History and physical exam: Individuals with a family member who has Factor V Leiden Thrombophilia should consider being tested as this is a risk factor for the disorder4. In the case presentation above, the patient was diagnosed after she was urged to undergo test by her primary care physician once her sister was diagnosed with the condition. Components in a patient history with Factor V Leiden Thrombophilia that will increase out of the ordinary clot formation are surgery, pregnancy, smoking, obesity, oral contraceptive pills, obesity, hormone replacement therapy, containing another mutation in the coagulation pathway and increasing age3. Symptoms include a DVT or PE that keep occurring, DVT before age 50 or age a young age, pregnancy loss in the second or third trimester that cannot be explained, or have a venous thrombosis take place in an out of the ordinary site4. Physical exam findings that may indicate a PE include dyspnea, tachypnea, and pain on inspiration5. Physical exam findings indicating a DVT include a warm to touch, unilateral extremity or area, swelling, and pain5. Also, the Wells criteria for predication of PE is very useful in the clinical setting5. However, in both a DVT and PE, there may be no presenting symptoms.

Diagnostic: Genetic testing where the individual’s DNA is analyzed for the F5 mutation or APC resistance and/or a coagulation screening test is used for diagnosis. Testing is strongly recommended if there is a family history of the disorder.

Management and treatment: Treatment and management is performed on a case by case basis as it depends on the individuals history and risks. Patients who are at low risk and have never had a PE or DVT may be treated with clinical observation as well as counseling on eliminating other risk factors and presenting symptoms to monitor oneself for4. If an individual only had one PE or DVT, lifelong anticoagulation is typically not necessary unless that person has other risks present4. Anticoagulation may be given as prophylaxis in these individuals in procedures that are high risk such as major surgery. At UMASS, all surgical patients are placed on some type of DVT prophylaxis prior to surgery as witnessed during the general surgery rotation. Individuals who are high risk, such as those with recurrent PE or DVT, should be placed on indefinite anticoagulation using agents such as Heparin4.

References
1. Reference G. F5 gene. Genetics Home Reference. 2017. Available at: https://ghr.nlm.nih.gov/gene/F5. Accessed March 16, 2017.
2. Berkowitz A. Clinical Pathophysiology Made Ridiculously Simple. 1st ed. Miami Florida: MedMaster Inc.; 2007:129-132.
3. Reference G. factor V Leiden thrombophilia. Genetics Home Reference. 2017. Available at: https://ghr.nlm.nih.gov/condition/factor-v-leiden-thrombophilia#synonyms. Accessed March 16, 2017.
4. Learning about Factor V Leiden Thrombophilia. National Human Genome Research Institute (NHGRI). 2017. Available at: https://www.genome.gov/15015167/learning-about-factor-v-leiden-thrombophilia/. Accessed March 16, 2017.
5. Papadakis M, McPhee S, Rabow M. Current Medical Diagnosis & Treatment 2015. 1st ed. San Francisco: McGraw Hill Medical; :293-297.