Rheumatology/Endocrinology! Jeopardy Template

Inflammatory or Non-inflammatory? That is the question.

Let's chase Zebras!

Rapid Rheumatology!

Doc! What can I do????

Great........Hormones.

100

A 66-year old man is evaluated for a 10-year history of pain affecting the fingers and bases of the thumbs, hips, and knees. Morning stiffness lasts less than 15 minutes, and pain is worse with activity.

PE reveals bony hypertrophy of the distal and proximal interphalangeal joints of the hands and squaring of the thumb bases bilaterally. Bony enlargement of medial knees and crepitus on ROM are noted. There is no soft-tissue swelling, warmth, or effusion.

Which of the following is the most appropriate test?

(A) Antinuclear antibodies

(B) Rheumatoid factor

(D) Synovial fluid analysis

(E) No additional laboratory studies

Answer is (E)

No additional laboratory studies are need. Osteoarthritis (OA) diagnosis is based on history and PE; radiography is confirmatory but may not be necessary. This patient has non-inflammatory arthritis, as evidenced by minimal morning stiffness and no evidence of warmth, soft-tissue swelling, or effusion; these findings further support the diagnosis of OA.

Additional testing for (A) ANA or (B) Rheumatoid factor is not needed. The cardinal signs of inflammation are pain, erythema, swelling, and warmth; with the exception of pain, non-inflammatory conditions usually lack these features.

(C) Lyme arthritis is an infectious arthritis with an inflammatory synovial response. It is usually monoarticular and occasionally polyarticular. This patient does not have findings suggestive of inflammatory arthritis, testing is not necessary.

(D) Synovial fluid analysis is helpful if effusion is present and there is concern about other causes of arthritis, such as concurrent crystal arthritis, infections, or other inflammatory causes.

100

Non-inflammatory vasculopathy notable for stenosis or occlusion of the arteries around the Circle of Willis and comes from the Japanese word meaning obscure, or hazy, like a puff of smoke.

Moyamoya disease.

100

Autoantibody associated with polymyositis, ILD, Raynaud's, fevers and mechanic hands.

Anti-synthetase autoantibodies/anti-JO-1

100

A 36 year-old woman is evaluate during a routine wellness visit. She is asymptomatic and has no medical problems. She works as an accountant and rarely engages in physical activity. She drinks a glass of red wine with dinner five times weekly. Her diet is rich in protein and starches and low in fruits, vegetables, and nuts. She has smoked one pack of cigarettes per day for 5 years. Her mother has rheumatoid arthritis, and the patient is concerned that she might also develop the disease. Her only medication is a combined OCP. PE is normal.

Which of the following is most likely to reduce this patient's risk for developing rheumatoid arthritis?

(A) Alcohol cessation

(B) Discontinuation of OCP

(D) Mediterranean Diet

(E) Smoking cessation

Answer is (E) - Smoking Cessation

Counseling for smoking cessation is the intervention that will most likely reduce this patient's risk for developing RA. A dose-dependent relationship exists between smoking and the development of seropositive RA. The risk of RA increases with an increasing number of smoking pack-years, and the risk decreases as the interval of smoking cessation increases.

A reduced risk for RA has been associated with moderate alcohol consumption in some observational studies. There is no reason for this patient to discontinue alcohol consumption to reduce her risk. (A)

(C) Increasing physical activity has been inconsistently associated with a reduced risk for developing RA. This recommendation should NOT be based on the possibility of reducing the risk of RA, although can be used for other reasons.

(D) The Med. diet has NOT specifically shown to reduce the risk for RA. Higher intake of fish may be associated with a lower risk, but studies on this association are inconclusive, as are studies on the effect of red meat, coffee, and use of antioxidants.

100

An 81-year-old man is evaluated for 3-month history of fatigue, constipation, cognitive symptoms, and cold intolerance. He has gained 10 pounds during the past year. Medical history significant for CAD. Medications are rosuvastatin, lisinopril, metoprolol, and aspirin. On physical examination, pulse rate is 54 bpm. Weight is 143 pounds. The thyroid is firm but not enlarged, the skin is cool and dry, and his hair is coarse. Deep tendon reflexes are delayed. Laboratory studies show a TSH level of 25 microunits/mL and free thyroxine level of 0.5 ng/dL.

Which of the following is the most appropriate treatment?

(A) Levothyroxine, 25 ug/d

(B) Levothyroxine, 100 ug/d

(D) Triiodothyronine, 50 ug/d

The answer is (A).

The most appropriate treatment is levothyroxine, 25 mcg/dL. This patient has overt primary hypothyroidism. He has the classic symptoms of fatigue, constipation, cold intolerance, cognitive symptoms, and dry hair and skin with physical findings of delayed deep tendon reflexes and bradycardia. Levothyroxine is recommended as the preparation of choice for the treatment of hypothyroidism because of its efficacy and resolving symptoms of hypothyroidism, long-term evidence of benefits, favorable adverse effect profile, ease of administration, good intestinal absorption, along serum half-life, and low cost.

Beginning with a full replacement dose of 1.6 mcg/kg lean body weight, which for this patient would be levothyroxine at 100 mcg/dL (B), is appropriate for most patients with overt hypothyroidism; however, in older adults in patients with cardiovascular disease, lower initial doses are recommended.

Studies of hypothyroidism treatment have failed to show clear benefit for T3 replacement alone, such as T3 at 50 mcg/dL (D) for this patient, or in combination with levothyroxine, including desiccated thyroid at 60 mg/dL (C).

200

A 27-year old woman is evaluate for a 4-year history of progressive achy and stiff low back pain that wakes her up at night and a 2-year history of intermittent, severe, sharp bilateral buttock pain. She has stiffness for 90 minutes each morning. Exercise and ibuprofren help relieve pain. She has a history of unilateral uveitis. She has no children.

On PE, vital signs are normal. ROM of the lumbar spine is decreased in all direction. The eye examination, occiput-to-wall distance, chest expansion, and peripheral joints are normal.

Laboratory studies reveal an elevated CRP and negative HLA-B27 antigen result. Radiographs of the pelvis and lumbar spine are normal.

Which of the following ist he most appropriate diagnostic test to perform next?

(A) Bone scanning

(B) CT of the pelvis

(D) Rheumatoid factor and anti-CCP antibodies

The answer is (C) MRI.

This patient has symptoms of inflammatory back pain with sacroiliitis consistent with ankylosing spondlyitis. She has developed symptoms at a young age (< 45 years) and has morning stiffness, nightttime pain, improvement with exercise and ibuprofren, and a history of uveitis. Her decreased ROM of the lumbar spine in all directions is typical of this disease. When plain radiographs are normal and the clinical suspicion is high, MRI of the pelvis may reveal erosions, edema, fatty metaplasia, and changes of inflammation (synovitis, enthesitis, or capsulitis) along the SI joints. Later in the disease, radiographs of the SI joints may show narowing, erosions, sclerosis, or fusion. Later findings on plan radiographs of the lumbar spine may reveal early squaring of the vertebral bodies, followed by syndesmophyte formation.

(A) Bone scanning is sensitive in the diagnosis of inflammatory arthritis, and a negative scan does exclude inflammation; however, this test is rarely used in the diagnosis of sacroiliitis because it is non-specific.

(B) CT scan of the pelvis may show bony changes, but CT exposes the patient to more radiation, it is not appropriate unless the patient cannot undergo MRI.

(D) These are diagnostic tests for RA. RA does not affect the lumbar spine and although RA does have eye involvement, it is typically scleritis rather than uveitis.

200

30-year-old woman is evaluated for a 2-month history of skin changes, primarily on her chest and arms. She has no other symptoms. Her only medication is an oral contraceptive. On physical examination, vital signs are normal. The rash on her chest as shown. There is no evident scarring or lesions in the scalp or ears, hair loss, or joint swelling. The remainder of the examination is normal. Laboratory evaluation reveals an antinuclear antibody titer of 1:640 with speckled pattern: Result for anti-Ro/SSA antibody is positive.

Which of the following is the most likely diagnosis?

(A) acute cutaneous lupus erythematosus

(B) cutaneous leukocytoclastic vasculitis

(D) subacute cutaneous lupus erythematosus

The most likely diagnosis is answer (D).

SCLE appears as 1 of 2 variants: And alert and polycyclic photosensitive plaques on the back, chest, and extremities, or psoriasiform scaly plaques in a similar distribution. It does not scar but may resolved with temporary pigmentary changes. Fewer than 1 and 4 patients with SCLE has SLE, and as many as 1 and 3 cases are drug-induced. The latter may resolved with withdrawal of the causative agent. Up to 70% of patients with SCLE have an elevated ANA, with anti-Ro/SSA and anti-La/SSB being over represented.

The malar butterfly rash is characteristic of acute cutaneous lupus erythematosus (A); however, ACLE can also manifest as a maculopapular variant that is photosensitive and distributed over the chest, upper back, and arms. Both rashes have a range of presentation from pink to violet macules to scaly papules and plaques. Essentially all patient's with this have lupus and as such tend to have systemic symptoms and positive serologic results. The rash does not scar.

Cutaneous leukocytoclastic vasculitis (B) results from inflammation of small blood vessels and can be seen in isolation or in association with a variety of systemic diseases, including autoimmune disorders, but also infection, hypersensitivity to medications, and malignancy. Rashes consist of red or purple discrete skin lesions, are more common on the lower extremities and on the trunk or forearms, and rarely occur on the face.

Chronic cutaneous lupus erythematosus (CCLE) (C) defines a category of related skin diseases of which discoid lupus erythematosus is the most common. DLE lesions started as red to violet plaques that developed a hyperpigmented border and thick adherent scale in the center. The centers of these lesions he eventually become atrophic and depigmented, causing permanent alopecia if occurring in the hairbearing areas. Plaques favor the head and neck, particularly in the scalp and the hollow of the auricle of the ear. CCLE in general has a low association with lupus, and DLE poses approximately 10% risk for underlying systemic disease.

200

Most commonly affected joint in a patient with septic arthritis.

The knee.

200

A 30-year-old woman is seen in follow-up. She was diagnosed with SLE 12 years ago. She was treated for lupus nephritis, which is now quiescent. Clinical and lab findings have been stable for 5 years, with no disease flares. Medications are Plaquenil (HCQ) and Imuran (Azathioprine).

Which of the following health risk assessments should be performed now?

(A) Breast Cancer

(B) CV Disease

(D) Pulmonary Disease

The answer is (B)

The most appropriate assessment to perform is for CVD risk. Patients with SLE have a high risk for CVD compared with the general population. Control of the underlying SLE may be the most important way to minimize this risk, but patients should also be screened for other modifiable risk factors. Assessment of diet, exercise, HTN, DM, smoking, and potentially lipids are indicated in patients, including young patients, with SLE.

(A) Breast cancer risk does not seem to be increased, but appropriate screening should be initiated in the future as indicated by guidelines.

(C) In patients with SLE, autoimmune hemolytic anemia occurs in approximately 10% and correlates with disease activity. Lymphopenia/leukopenia is common but usually mild. Thrombocytopenia occurs in 30% to 50% of patients, and approximately 10% develop severe thrombocytopenia (plt ct < 50,000/uL) in isolation or in conjunction with hemolytic anemia. Iron overload syndromes, such as hemochromatosis, are not a morbidity of SLE unless associated with increased transfusion requirements.

(D) Some patients with SLE or overlap syndromes can have ILD that would warrant additional testing. However, this patient is asymptomatic, and assessment for pulmonary disease is not warranted.

200

32-year-old woman is evaluated for 3-month history of galactorrhea, fatigue, constipation, and weight gain of 8 pounds. With the onset of galactorrhea, her menstrual periods have become irregular and associated with excessive bleeding. Her most recent menstrual period was 5 weeks ago. She has no other medical concerns and takes no medications. On physical examination, vital signs are normal. BMI is 28. Spontaneous galactorrhea is present. Visual fields are intact. Deep tendon reflexes are delayed. The remainder of her physical exam is normal. Human chorionic gonadotropin testing is negative. Serum prolactin level is 68 ng/mL.

Which of the following is the most appropriate management?

(A) Cabergoline therapy

(B) Estrogen and progresterone therapy

(D) TSH measurement

The answer is D.

The most appropriate management is to measure TSH. The most common cause of hyperprolactinemia is physiologic, related to pregnancy and lactation. Physiologic stress, colitis, sleep, and nipple stipulation are other nonpathologic causes of mild hyperprolactinemia. The most common cause of pathologic none tumor related hyperprolactinemia is medication; however, other causes of hyperprolactinemia must be considered for this patient. Her symptoms of fatigue, constipation, weight gain, and menorrhagia are consistent with hypothyroidism. Overt primary hypothyroidism as a cause of hyperprolactinemia. The mechanism of hyperprolactinemia and hypothyroidism is related to release of TRH from the hypothalamus, which stimulates both TSH and prolactin. Very patient presenting with both hyperprolactinemia and hypothyroidism, the hypothyroidism should be treated first and then the prolactin level should be retested to ensure that the hyperprolactinemia has resolved.

In patients with macroadenomas, dopamine agonist therapy is recommended to lower prolactin, reduce tumor size, and restore gonadal function. Cabergoline (A), a dopamine agonist, is the preferred agent because of its superior efficacy in lowering prolactin and tumor shrinkage compared to bromocriptine. Although cabergoline is an appropriate therapy for patient with hyperprolactinemia caused by a prolactinoma, this patient's hyperprolactinemia may be explained by hypothyroidism.

Further evaluation is needed before initiating estrogen/progesterone therapy (B) to treat this patient's amenorrhea and to prevent bone loss. If hypothyroidism is the cause of this patient's hyperprolactinemia and menstrual irregularities, and if this patient does not currently want to become pregnant, estrogen/progesterone replacement therapy is reasonable.

Pituitary MRI (C) is not indicated at this time because this patient's hyperprolactinemia may be explained by hypothyroidism and there is no evidence of mass effect. If hypothyroidism is diagnosed, it will be necessary to ensure that the hyperprolactinemia normalizes after treatment with levothyroxine. If the prolactin level does not normalize, pituitary MRI is indicated.

300

A 37-year-old woman is evaluated for 1 year history of widespread joint and muscle pain, fatigue, poor sleep, and difficulty focusing. She also has irritable bowel syndrome and migraine headaches. Current medications are sumatriptan and topiramate. On physical examination, vital signs are normal. No rashes present on the face or extremities. Joint examination shows normal range of motion and no joint swelling. No soft tissue is tender to light palpation. Muscle strength is normal. Laboratory evaluation shows a normal CBC, serum TSH, and urinalysis as well as an erythrocyte sedimentation rate of 20 mm/h.

Which of the following is the most likely diagnosis?

(A) fibromyalgia

(B) generalized osteoarthritis

(D) rheumatoid arthritis

(E) SLE

The most likely diagnosis is fibromyalgia (A).

This patient presents with widespread pain, fatigue, poor sleep, and cognitive symptoms of 1 years duration. The symptoms are the hallmarks of fibromyalgia, poorly understood but common chronic pain syndrome affecting 2% to 3% of the population. Diagnosis is suggested by history and can be confirmed with validated criteria such as the 2016 revisions to the ACR preliminary diagnostic criteria. This illness is not autoimmune or inflammatory, and extensive laboratory testing is not advised unless another comorbid disease is suggested. Although some patients may have tender points, assessment of tender points on examination is unreliable and no longer among the clinical criteria for diagnosis. Fibromyalgia tends to be associated with other medically unexplained syndromes, including IBS, and is especially common in patients with migraine headaches.

Generalized osteoarthritis (B) affects multiple joint groups. On joint examination, crepitus, decreased range of motion, bony enlargement, and sometimes effusion may be present. Generalized osteoarthritis is an unlikely diagnosis which could it was not caused widespread pain seen in this patient and occurs in older patients. In addition, the examination demonstrates no evidence of osteoarthritis in any joint.

Polymyalgia rheumatica (PMR) (C) is a clinical diagnosis based on characteristic symptoms in a patient older than 50 years and is supported by an elevated erythrocyte sedimentation rate. PMR is associated with pain and stiffness of the shoulder girdle and hip girdle. This patient's age, diffuse pain, and normal ESR are not compatible with PMR.

Rheumatoid arthritis (D) is an inflammatory arthritis that primarily affects small joints. Patients with rheumatoid arthritis present with discomfort in discrete joints, not diffuse pain. In addition, rheumatoid arthritis does not cause axial pain or myalgia. The musculoskeletal examination in a patient who has a 1 year history of untreated rheumatoid arthritis should reveal multiple swollen joints.

Systemic lupus erythematosus (SLE) (E) is an autoimmune disease that can affect any system in the body, including the skin, blood cells, joint, lung, CNS, and kidneys. Although patients with SLE can have concurrent fibromyalgia, patients with fibromyalgia really have lupus. This patient also has none of the hallmarks of lupus, such as autoimmune cytopenia, inflammatory arthritis, rash, kidney disease, or systemic inflammation.

300

A 23 year-old man is evaluated for fever, abdominal pain, rash, and arthritis of the right knee of 3 days' duration that resolved 1 week ago. He has had more than 20 similar episodes, the last three occurring in the past year. The first episode occurred at age 5 years and presented as abdominal pain; the patient underwent appendectomy but no appendicitis was found. His paternal grandfather and maternal grandmother had a similar syndrome.

PE is normal.

Lab evaluation shows an ESR of 23 mm/h, a normal serum Cr, and 1+ protein on urinalysis.

Which of the following is the most appropriate treatment?

(A) Canakinumab

(B) Colchcine

(D) Prednisone

Answer: B

Autoinflammatory syndromes are monogenic diseases that result in periodic episodes of systemic inflammation. The constellation of symptoms in this patient is characteristic of familial Mediterranean fever (FMF), a disease driven by several mutations in the MEFV gene and is mostly common in those with Jewish, Arab, and Turkish descent. First-line treatment is LIFE-LONG daily prophylaxis with colchicine.

Canakinumab (A) is a monoclonal antibody to IL-1B that has been reported to successfully treat patients with FMF, including those in whom colchicine has failed. However, this medication is $$$, immunosuppressive, and has not been FDA approved yet. This medication should be reserved for patients with FMF in whom colchicine has failed or is not tolerated.

NSAIDs, such as Indomethacin (C), may alleviate symptoms but do not address the underlying mechanism of FMD and are not appropriate preventative or long-term therapy.

Glucocorticoids, such as prednisone (D), may decrease the duration of attacks but also increase their frequency. Thus, they are not appropriate for long-term or preventative FMF therapy.

300

Name one other disease that have a positive RF.

1. COPD

2. Viral hepatitis

3. Sarcoidosis

4. Malignancy

5. Primary biliary cirrhosis

*The higher the titer, the more likely it is RA*

300

A 56 year-old man is evaluated during a wellness visit. he has an 18-year history of type 2 DM. He is in good health. His vaccinations are current for influenza and COVID-19, and he received the 23-valent pneumococcal polysaccharide vaccine 3 years ago and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine 6 years ago. He also received the measles, mumps, rubella vaccine as a child. Medications are atorvastatin and metformin.

Which of the following is the most appropriate vaccination to recommend at this time?

(A) Hepatitis B

(B) Quadrivalent meningococcal conjugate

(D) 13-Valent pneumococcal conjugant

The correct answer is (A) Hepatitis B.

Patients with type I and type 2 diabetes may be at high risk for hepatitis B because of contact with equipment that contains infected blood, such as unsterile needles or blood glucose monitoring devices. The advisory committee on immunization practices (ACIP) recommends hepatitis B vaccination in patients with diabetes age 18 through 59 years; vaccination in patients with diabetes age 60 years and older is at conditions discretion.

ACIP recommends routine vaccination with the quadrivalent meningococcal conjugate vaccine (B) for children age 11 or 12 years, with a booster dose at age 16 years. It is also recommended for some adults, including those with complement deficiency, those with functional or anatomic asplenia, HIV, and travelers and residence countries in which the disease is common. Diabetes is not an indication for meningococcal vaccination.

Adults age 19 years and older should receive a tetanus and diphtheria toxoid (Td) vaccine (C) or the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) booster every 10 years. In adults we did not receive the Tdap during adolescence, at least one of the 10-year booster doses should be with the Tdap vaccine. This patient received the Tdap 6 years ago and does not require revaccination at this point.

Diabetes is not an indication for the 13 Valent pneumococcal conjugate or PCV 13 vaccine (D). It is indicated in patients with specific immunodeficiencies, anatomic or functional asplenia, sickle cell disease or other hemoglobinopathies, and then those with cerebrospinal fluid leak or cochlear implant. At age 65 years, patient should be engaged in shared decision making regarding PCV 13 vaccination.

300

33-year-old man is evaluated for tremulousness, nausea and vomiting, palpitations, dyspnea on exertion, and a 15 pound weight loss during the past month. His medical history is significant for graves disease diagnosed 3 months ago that was controlled on methimazole and propranolol. He stopped taking the eat in half an hour he stopped taking the methimazole 1 month ago. On physical examination, temperature is 103 °F, blood pressure is 80 over 50 mm Hg, pulse rate is 135/min and irregular, respiratory rate is 28/min, and oxygen saturation is 93% breathing ambient air. Cardiac examination reveals a rapid irregular rhythm, jugular venous distention, and bilateral pulmonary crackles. Thyroid stimulating hormone level is less than 0.01 uU/mL and free thyroxine (T4) level is 10.0 ng/dL. Chest radiograph shows pulmonary congestion. ECG reveals atrial fibrillation.

Which of the following is the most appropriate immediate management?

(A) ICU admission

(B) Methimazole and propranolol reinitiation

(D) Thyroidectomy

The answer is (A)

The most appropriate management for this patient is ICU admission. He has severe thyrotoxicosis with evidence of cardiac compromise, consistent with thyroid storm. Thyroid storm is differentiated from severe thyrotoxicosis by the presence of life-threatening complications such as hemodynamic compromise; occurs often with discontinuation of antithyroid drug therapy, systemic illness, labor and delivery, surgery, or trauma. It has a high mortality rate of up to 30% and requires intensive care for any precipitating illness, thyroid toxicosis directed therapy, and supportive measures. Thyroid storm is treated with intravenous beta-blockers such as esmolol; thionamides, typically PTU, transitioning to methimazole when more stable; intravenous high-dose glucocorticoids; and potassium iodide. To avoid providing iodine substrate to the gland, iodide should be administered more than 1 hour after antithyroid drugs. Glucocorticoid therapy is a potent inhibitor of peripheral T4-T3 conversion. Bile acid sequestrant's can be used to decrease T4 and T3 levels, especially in patients unable to take thionamides. Plasmapheresis or emergent thyroidectomy is used in patients who experience a poor response to medical therapy.

Methimazole and propranolol reinitiation (B) would treat the thyrotoxicosis and improve the tachycardia. However, there affects require significant time, and this patient's compromised hemodynamic status requires close monitoring, additional emergent therapy, and supportive care.

Although supersaturated potassium iodine administration (C) rapidly decreases thyroid hormone production through the will try cough affect, excess serum iodide inhibiting organic fixation of iodide and subsequent thyroid hormone release, it is critically important to initiate antithyroid thionamides drugs at least 1 hour before starting supersaturated potassium iodide to prevent rapid incorporation of the iodine load, which would worsen the thyrotoxicosis.

Definitive treatment with thyroidectomy (D) or iodine-131 therapy is indicated in patients who survived thyroid storm. However, thyroidectomy in patients with uncontrolled severe thyrotoxicosis is associated with a high mortality rate and should be avoided if at all possible.

400

45-year-old man is hospitalized for incapacitating polyarthralgia and fever. 1 week before hospitalization, pain in multiple joints of the hands, wrists, elbows, ankles, and feet developed over the 24-hour period. 5 days before hospitalization, fever, malaise, and intensification of the joint pain developed. 2 days before hospitalization, rash appeared on the extremities and trunk and spread to the face. He lives in southern Florida and has not recently traveled outside the United States. On physical examination, temperature is 39.1 °C, 102.4 °F, and pulse rate is 116/min. He has bilateral conjunctivitis and a maculopapular rash on the face, extremities, and trunk. Joint examination shows swelling and tenderness of the proximal interphalangeal joints, metacarpophalangeal joints, wrists, elbows, ankles, and metatarsal phalangeal joints.

Infection with which of the following is the most likely diagnosis?

(A) Chikungunya virus

(B) Hepatitis B virus

(D) HIV

The answer is (A)

Infection with chikungunya virus is the most likely diagnosis. Chikungunya is an arbovirus spread by mosquitoes. Acute infection is heralded by the abrupt onset of severe, polyarticular arthralgia and fever, and exanthema that may be focal or diffuse, and conjunctivitis. The distribution of the arthritis is often bilaterally symmetric and usually involves 10 or more joints. The temperature is often greater than 39.0 °C / 102.2 °F, and fever persist for 3 to 5 days. Laboratory testing revealed leukopenia, lymphopenia, thrombocytopenia, and elevated serum aminotransferase and creatinine levels. This virus can be detected by PCR for 1 week after onset of symptoms, after which testing becomes unreliable. Specific IgM antibody is detectable in 5 to 10 days after symptom onset and remains positive for up to 2 to 3 months. This patient's intensity of pain, large number of joints involved, high temperature, and residence in stomach area make this viral illness the most likely diagnosis.

Acute hepatitis B infection (B) may be accompanied by an abrupt, severe onset of polyarticular joint pain that antedates and terminates with the onset of jaundice. However, it is not associated with an acute febrile onset or widespread maculopapular rash: Other skin findings, such as urticaria, small vessel vasculitis, and erythema multiforme, have been associated with acute hepatitis B virus infection.

Hepatitis C infection (C) is largely asymptomatic but occasionally is accompanied by polyarthritis. However, it is not associated with an acute febrile onset or maculopapular rash. It is associated with cryoglobulinemia, arthralgia may be seen but the rashes purpuric. Other skin manifestations may include livedo reticularis, erythema multiforme, and lichen planus.

HIV infection (D) is associated with several musculoskeletal syndromes. Although the painful articular syndrome is characterized by an abrupt onset of arthralgia myalgia, is not associated with fever, is illegal articular and asymmetric, most frequently involves the joints of the lower extremities, and typically resolves within a day. HIV-associated arthritis, reactive arthritis, and psoriatic arthritis are sometimes seen in patients with HIV infection but do not happen acute onset are not associated with fever and rash.

400

39-year-old woman is evaluated for newly discovered neutropenia. She has a 10-year history of severe, difficult to control rheumatoid arthritis. She has no sicca symptoms. Current medications are prednisone, methotrexate, folic acid, and adalimumab. On physical examination, vital signs are normal. There are rheumatoid nodules over the olecranon processes. The spleen tip is palpable. Joint examination reveals unlearn deviation, subluxation at the metacarpal phalangeal joints, reduced range of motion of the risks, and bilateral swelling of the wrist and left ankle.

Laboratory studies show an absolute neutrophil count of 1100/uL, leukocyte count of 3800/uL, absolute lymphocyte count normal, platelet count normal, urinalysis normal.

Which of the following is the most likely diagnosis?

(A) AA amyloidosis

(B) Felty syndrome

(D) SLE

The most likely diagnosis is (B) Felty syndrome.

This syndrome is a complication of well-established RA characterized by neutropenia and splenomegaly. Patients with Felty syndrome are at risk for serious bacterial infections, lower extremity ulceration, lymphoma, and vasculitis. Patients may present with an asymptomatic decline in the neutrophil count that is detected on routine lab testing for medication toxicity. Because a decline in leukocyte count can also be an adverse effect of numerous medications used to treat RA, it is important to evaluate for this possibility. However, medications are far likely to reduce the neutrophil count and are not likely to be associated with splenomegaly. Some patients may present with an infection related to neutropenia, so in this instance the total leukocyte count may be normal at the time of presentation but fall with treatment of the infection. Patients with RA can also have large granular lymphocytic leukemia, which an progress to large granular lymphocytic leukemia. Findings overlap with Felty syndrome and include neutropenia, anemia, thrombocytopenia, splenomegaly, and recurrent infections.

(A) AA amyloidosis is a rare complication of long-standing and poorly controlled RA. In a minority of patients, it can lead to splenomegaly as a consequence of infiltration of the spleen by amyloid protein. However, AAA amyloidosis would not be expected to result in neutropenia, make it an unlikely diagnosis in this patient.

Patients with rheumatoid arthritis may develop an overlap syndrome characterized by features of another autoimmune disease, such as Sjogren's syndrome (C) or SLE (D). However, the patient would not be designated as having an overlap syndrome in the absence of typical features of the other autoimmune disease.

400

In Sjogren's, presence of subpleural honeycombing is suggestive of what ILD pattern, which portends the worse prognosis?

Usual Interstitial Pneumonitis (UIP)

400

60-year-old woman is evaluated during a follow-up visit for hypertension, coronary artery disease, obesity, and dyslipidemia. She reports 11 pound weight gain in the past year. Her fasting blood glucose was 110 mg/dL and hemoglobin A1c level of 6.1% 6 months ago. Current medications are hydrochlorothiazide, lisinopril, carvedilol, low-dose aspirin, and atorvastatin. On physical examination, blood pressure is 135 over 84 mm space Hg. BMI is 28. The remainder of the exam is normal. Fasting glucose was 114 mg/dL.

Which of the following is the most appropriate management for this patient's prediabetes?

(A) Glipizide

(B) Intensive lifestyle modification

(D) Sitagliptin

The answer is (B).

Intensive lifestyle modification should be implemented to delay or prevent the development of type 2 diabetes mellitus. Prediabetes is defined as a hemoglobin A1c level between 5.7% and 6.4%, fasting blood glucose between 101 mg/dL and 125 mg/dL, or impaired glucose tolerance test with 2-hour glucose between 140 mg/dL and 199 mg/dL after about 75 g oral glucose load. This patient had 3 laboratory tests results consistent with prediabetes in the past 6 months. Lifestyle modifications have been shown to reduce the incidence of type 2 diabetes by 58% persons with diabetes. Patients with prediabetes should be retested yearly to monitor for the development of type 2 diabetes.

Glipizide, a sulfonylurea, is not indicated as a treatment for diabetes prevention. In addition, glipizide is associated with weight gain.

In contrast, metformin has demonstrated efficacy and diabetes risk reduction. In the diabetes prevention program, metformin was not as effective as lifestyle modification but used the incidence of diabetes by 31% compared with placebo and by 18% at 10-year follow-up. Metformin may be considered for prevention of type 2 diabetes in patients with prediabetes unresponsive to lifestyle modifications, particularly in patients with BMI greater than 35, age younger than 60 years, or history of gestational diabetes. If this patient fails to lose weight, metformin would be a reasonable addition.

Although weight neutral, Sitagliptin, a DPP-4 inhibiitor, is not indicated as a treatment for diabetes prevention

400

42-year-old woman is evaluated for 3-month history of fatigue, weakness, anorexia, and weight loss. She has episodes of light headedness when she moves from sitting to standing too quickly. Her medical history is significant for autoimmune hypothyroidism. Her only medication is thyroxine. On physical exam, blood pressure is 110/70 and pulse rate is 92 bpm. A decrease of 10 mmHg and blood pressure occurs on standing. The remainder of the vital signs is normal. Other than dark and palmar creases, the remaining examination is normal. Comprehensive metabolic profile is remarkable only for serum sodium level of 135 mEq/L and serum potassium level of 5.4 mEq/L. An 8 AM serum cortisol level is 2 mcg/dL.

Which of the following is the most appropriate next diagnostic tests?

(A) Abdominal CT

(B) Adrenocorticotropin hormone measurement

(D) 24-hour urine cortisol measurement

The answer is (B)

The most appropriate next diagnostic test is adrenal corticotropin hormone measurement. Primary adrenal insufficiency is a life-threatening disorder that often presents with insidious onset of symptoms, masking diagnosis a challenge. He may also present has adrenal crisis, often precipitated by an acute illness or the initiation of thyroid hormone replacement in a patient with unrecognized chronic adrenal insufficiency. Close that the diagnosis in this patient include the presence of orthostatic changes in blood pressure, hyperpigmentation of the palmar creases, hyponatremia, and hyperkalemia. The morning serum cortisol, a test for adrenal insufficiency, was less than the screening threshold of 3 uU/dL. The next diagnostic test is measurement of serum ACTH; an elevated value indicates primary adrenal insufficiency, where as low or inappropriate normal values indicate secondary (pituitary) or tertiary (hypothalamic) adrenal insufficiency.

Abdominal CT (A) is not the most appropriate next diagnostic test. The most common cause of primary adrenal insufficiency is autoimmune adrenalitis. 21-hydroxylase antibodies are present and approximately 90% of patients with autoimmune adrenalitis. If patients with adrenal insufficiency are antibody negative, CT of the adrenal gland should be obtained to help identify other causes of adrenal insufficiency, such as hemorrhage, infiltrative diseases, or metastatic cancer.

An ACTH stim test (C) would be indicated if morning cortisol were in the indeterminate range of 3-15 micrograms per deciliter. In this situation, normal response to the high-dose ACTH stim test would exclude the diagnosis of primary adrenal insufficiency. An ACTH stim test may also be considered to confirm a diagnosis of adrenal insufficiency, but it is not the next diagnostic test in this patient.

24-hour urine cortisol measurement (D) is not indicated in this patient. Normal values and values associated with partial adrenal insufficiency can overlap, reducing his value is a screening test. In addition, insufficient cortisol production has already been established with a low morning cortisol level.

500

A 45-year-old woman is evaluated for progressive shortness of breath for 6 months, hearing impairment, and knee pain. She has no additional medical problems and takes no medications. On physical examination, vital signs are normal: Oxygen saturation is 98% with the patient breathing ambient air. She has swelling and redness of the helicis of the ear, with sparing of the lobule; Diminished hearing bilaterally; Bilateral conjunctivitis; and redness, tenderness, and flattening of the nasal bridge. Lung examination reveals inspiratory stridor loudest over the trachea. Knees show joint line tenderness bilaterally. The remainder of the physical examination is normal. Laboratory test, chest radiography, and CT of the upper airways and chest are ordered.

Which of the following is the most likely diagnosis?

(A) Cryoglobulinemia

(B) GPA

(D) Rheumatoid arthritis

The most likely diagnosis is relapsing polychondritis (C).

This patient has a chronic inflammatory disease involving the cartilage of the ears, nasal bridge, joints, and trachea, as well as involvement of the connective tissue of the eye. Hearing loss is likely related to inflammation of the middle ear cartilage. Because relapsing polychondritis is a clinical diagnosis for which no specific test exists (although certain autoantibodies, including those to type II collagen, may be supportive), other causes should be considered and ruled out as appropriate. Management depends on severity: NSAIDs and dapsone for mild symptoms and high-dose glucocorticoids for initial management of acute and/or severe involvement. Oral immunosuppressants such as methotrexate may be added. The tumor necrosis factor inhibitors infliximab and adalimumab and the antiinterleukin 6 agent Toculizumab may also be effective.

Like relapsing polychondritis, cryoglobulinemia (A) can affect the ears and nose. However, cryoglobulinemic involvement of these tissues typically ischemic/necrotic rather than inflammatory and usually affects the tip rather than the bridge of the nose. Cryoglobulinemia can affect the milligrams but not the trachea. Moreover, most cryoglobulinemia is except for type I R secondary to hep C viral infection or primary autoimmune disease; testing for hepatitis C virus and autoimmune antibodies can be considered.

Like relapsing polychondritis, granulomatosis with polyangiitis (B) can affect the upper and lower airways, ears, and eyes and can cause a saddlenose deformity. It can also cause arthralgia, although the arthralgia is usually migratory. However, GPA involvement of the lungs is typically parenchymal and does not involve the trachea. Because 90% of patients with GPA are positive for antiproteinase 3 antibodies, testing can be considered.

Rheumatoid arthritis (D) can involve the knees symmetrically and in severe presentation can cause a systemic illness that involved eyes and glottis. However, it does not typically affect the ears or trachea. This patient also lacks the classic symmetric probably arthritis of the hands, and his knee pain severity is not commensurate with severe rheumatoid arthritis.

500

72-year-old woman is evaluated for a 3-month history of abdominal and back pain and 4-month history of an increasingly rounded face. On physical examination, vital signs are normal. BMI is 29. Bilateral lacrimal and parotid glands are enlarged. Laboratory evaluation shows a hemoglobin A1c value of 5.4%, and alkaline phosphatase level of 255 units/L, and an estimated GFR of 59 mL/min per 1.73 m² (same as 1 year ago). An abdominal CT scan shows periaortitis with left retroperitoneal mass that extends bilaterally and encircles both ureters without hydronephrosis. Needle biopsy of the mass reveals dense fibrous tissue and a storiform pattern, interspersed with an inflammatory infiltrate, including increased numbers of IgG4 positive plasma blast. Serum IgG4 levels are not elevated.

In addition to prednisone, which of the following is the most appropriate treatment?

(A) Cevimeline

(B) Methotrexate

(D) Surgical debridement

The answer is (C) Rituximab.

The infiltrative involvement of the parotid and lacrimal glands, together with retroperitoneal fibrosis and periaortitis, is most consistent with IgG4 related disease. IgG4 positive plasma blast on biopsy confirmed the diagnosis. The absence of elevated serum IgG4 antibodies is not exclusionary because serum antibodies are often not present. Treatment of IgG4 related disease most often consists of initial high-dose glucocorticoids followed by a slow taper. Because the disease often recurs during taper, and because glucocorticoids. Significant toxicity, coadministration of rituximab is often initiated to permit accelerated glucocorticoid taper. However, rituximab monotherapy is also effective and can be used alone in patients with absolute or relative contraindications to glucocorticoid therapy.

Cevimeline (A) is a parasympathetic muscarinic agonist use to treat sicca in patients with Sjogren's syndrome. Because this patient has parotid enlargement, she might have sicca and might benefit from cevimeline. However, cevimeline has not been studied in the context of IgG4 parotitis, and the patient has not reported dry mouth.

Methotrexate (B) is a disease modifying antirheumatic drug used as a glucocorticoid sparing agent for many diseases, including ANCA vasculitis. Methotrexate has also been used extensively for idiopathic retroperitoneal fibrosis. However, limited evidence supports methotrexate to assist in glucocorticoid tapering or as a single agent and IgG4 related disease.

Surgical debridement of the retroperitoneal mass (D) may be necessary if the mass threatens to erode into the aorta, but that is not the case in this patient. The mass is wrapped around both ureters, however, there is no hydronephrosis or deterioration of kidney function to suggest obstructive nephropathy, which would require ureteral stent placement.

500

Antibody that is commonly seen in patients with dermatomyositis, amyopathic disease, mucocutaneous lesions, severe lung disease?

Anti-MDA5/anti-CAMD-140 antibodies.

500

!!!!!DAILY DOUBLE!!!!!

A 67-year-old man is evaluated for a 4-week history of headache and fatigue. He has metastatic melanoma and receives nivolumab every 2 weeks. The patient has otherwise been well and has no additional symptoms. He takes no other medications. On physical examination, vital signs are normal. Confrontational visual field testing is normal. No focal neurologic findings are present. On laboratory evaluation, adrenocorticotropin hormone and 8 AM serum's cortisol level was low. Chest radiograph is normal.

Which of the following is the most likely diagnosis?

(A) Hypophysitis

(B) Metastatic melanoma

(D) Sarcoidosis

The answer is (A).

Most likely diagnosis is immune checkpoint inhibitor related cough for situs (A). These drugs, including antiprogrammed death cell protein 1, anti-PD-1, (nivolumab or pembrolizumab) and an anticytotoxic T lymphocytes associated protein-4 (anti-CTL-4) (ipilimumab, tremelimumab, and pembrolizumab) antibodies, are used to treat many solid tumors. Hypophysitis occurs and 0.5% to 17% of patients and often presents with headache and fatigue. Hypophysitis is more common in patients manage with anti-CTL for antibodies or combination therapy, in men, and in older patients. Although endocrine evaluation usually reveals adrenocorticotropic hormone, luteinizing hormone, and thyroid-stimulating hormone deficiency, as well as low levels of growth hormone, adrenocorticotropic hormone deficiency is the most immediate concern because cortisol deficiency can be life-threatening. Imaging demonstrates enhancement or enlargement of the pituitary gland with thickening of the pituitary stalk. Diabetes insipidus is uncommon. Treatment includes replacement of the hormone deficiencies and high-dose glucocorticoids in severe cases to treat the inflammatory process, although hormone deficiencies often persist. It is important to replace cortisol before initiation of thyroid hormone to avoid precipitating an adrenal crisis.

With metastasis to the pituitary gland is rare. Breast cancer and lung cancer or other solid malignancies most likely to metastasize to the pituitary gland. Although anterior pituitary hormone deficiency can occur in pituitary medicine basis, diabetes insipidus is most often the initial presentation. In this case, hypophysitis is much more likely than metastatic melanoma (B).

Rapid expansion of a pituitary tumor caused by pituitary apoplexy (C), defined as sudden hemorrhage or infarction of the pituitary adenoma, typically causes sudden severe headache and compression of the optic chiasm and may also be associated with cranial nerve palsies of nerves III, IV, and 6. The patient's 4-week history of fatigue and headache are unlikely acute and traumatic symptoms typically associated with pituitary apoplexy.

Pituitary infiltrative disorders, most often sarcoidosis (D) in Langerhans cell histiocytosis, can cause deficiencies of anterior pituitary hormones and diabetes insipidus. Most patients with pituitary sarcoidosis have evidence of sarcoidosis elsewhere, typically in the lungs. Isolated pituitary sarcoidosis is rare, in the absence of diabetes insipidus also argues against this diagnosis.

500

A 61-year-old man is evaluated for recently diagnosed hypogonadism, for which testosterone therapy will be initiated. He has no history of prostate cancer, CVD, or venous thromboembolic disease. He has no symptoms of excessive daytime sleepiness. A previous digital prostate examination revealed no nodules or areas of asymmetry. Hematocrit level is normal.

Which of the following is the most appropriate next step before initiating testosterone therapy?

(A) Factor V Leiden screening

(B) Home sleep study

(D) Urology consultation

The answer is (C).

Potential adverse effects of testosterone replacement therapy include acne, prostate enlargement and prostate cancer, obstructive sleep apnea, thrombophilia, and erythrocytosis. The 2018 American urological Association guidelines recommend measuring PSA to exclude a prostate cancer diagnosis in men older than 40 years before starting testosterone therapy. The AUA also recommends the PSA test for patients with testosterone deficiency will maintain testosterone levels in the normal range, using a shared decision-making approach. The AUA does not recommend routine PSA testing in men age 40-54 unless they are at higher risk such as a positive family history or African-Americans, for whom PSA testing decisions should be individualized. In men aged 55 to 69 years, biennial PSA testing should be considered. The 2018 endocrine Society guidelines recommend that men who have begin testosterone treatment and are older than 50 years should be reevaluated for prostate cancer with PSA testing at 3 months and 1 year after beginning treatment and thereafter according to the standard of care. An increase in PSA greater than 1.4 ng/mL at 1 year or greater than 0.4 ng/mL after 6 months of testosterone use or abnormal results on digital rectal examination should prompt further investigation for prostate cancer. Hematocrit level should also be obtained at baseline and then at 3 months and 6 months after therapy initiation, followed by yearly measurements.

Venous thromboembolic disease risk is increased in men receiving testosterone replacement therapy. A careful family and personal history for VTE disease should proceed testosterone therapy. However, routine screening for thrombophilia with factor V Leiden (A) screening for or other thrombophilic disorders is not recommended.

The most important established consequence of OSA is excessive daytime sleepiness. Home sleep testing (B) does not measure electroencephalographic sleep as polysomnography does. However, home sleep testing is diagnostically similar and otherwise healthy patient's were suspected of having at least moderate to severe OSA. This patient has no symptoms to suggest OSA.

Urology consultation (D) should be obtained if the PSA level is elevated before the initiation of testosterone replacement therapy or if the palpable abnormality of the prostate gland is found. Routine referral for urology consultation is not indicated before starting testosterone replacement therapy.