Twenty Paper Cases Used in the Simulation Exercises
The Simulation Exercises are divided into two sections, each containing ten cases.

First Simulation Exercise

CASE 1
A 49-year-old male with established renal, lung and upper airways WG (conductive deafness, nasal blockage, and blood stained discharge) returns for follow-up at one year after onset. His main problems at the current visit are constant hearing loss, low mood (no change for 4 months), profound lethargy (for at least 6 months and no better or worse over that time). His weight has gone down 1 kg since his steroids were reduced last month. No mouth/genital ulceration. He has had purpura for the last week, associated with a drop in platelet count to 40K. He stopped his azathioprine 5 days ago, and his platelet count is now normal. The rash is still present but getting better, and there are no new lesions on his legs. He has had poor eyesight for the last 4 months due to steroid related early cataract and has noted dry eyes for the last 8 months. He has not had any chest or cardiovascular problems. He has had persistent proteinuria on dipstick (++) for 6 months, but no hematuria. He has had difficult-to-control hypertension for 10 months, and his BP is 160/98 today. He has a creatinine of 2.65 mg/dl (no change for 8 months). He does not have any focal neurological changes, but has a history of childhood epilepsy since age 7.

CASE 2
A 67-year-old female had WG diagnosed 4 years ago, when she presented with renal, lung, and ENT disease. She has now been off of treatment for 1 year. Over the past week she has developed diplopia, loss of vision in the left eye, and obvious proptosis of that eye. The eye is painful with some redness of the sclera. No ENT or joint symptoms. Some weight loss (2 kg in last month). Longstanding (>2 year) hypertension and proteinuria (+). Creatinine 3.40 mg/dl (no change for last 2 years). Angina within last year with some intermittent claudication for at least 6 months. No gastroenterological features (except constipation due to analgesic use – dihydrocodeine for eye pain). Examination reveals scleritis and proptosis of the left eye, with diplopia on lateral eye movements, associated with restriction of left eye movements. An urgent ophthalmology consult shows no retinal disease, and an MRI confirms the presence of a retro-orbital infiltrate consistent with WG.

CASE 3 – REVIEW
A 52-year-old lady returns for repeat evaluation six weeks after her initial diagnosis. She first presented with a three week history of arthralgia, weight loss, fever, nasal stuffiness, epistaxis, swollen salivary glands, purpura and is noted to be hypertensive. She has hematuria (4+) and proteinuria, creatinine of 1.7mg/dl. Investigations confirm the diagnosis of WG. She starts on treatment with cyclophosphamide and prednisone.

At this time she reports an improvement in general health. She is still getting some nosebleeds but they are less frequent (only three times a week); her salivary glands are still swollen but not as sore and look 50% better but still tender on palpation. Hematuria is present at 1+ on dipstick testing, but there is no proteinuria. On microscopic examination of her urine, she has broad, waxy casts but no RBC casts. Her creatinine is stable at 1.6mg/dl.

CASE 4
A 13-year-old girl presents with a six-month history of purpuric skin lesions on both legs, associated with ulceration around the right ankle. There are no obvious precipitating causes. Cutaneous biopsy shows a leukocytoclastic vasculitis. For the past three months she has noticed a constant blood stained nasal discharge and frequent golden/red crusts from both nostrils. She also complains of increasing pains in her ankles, knees and hands. She is not aware of any fevers. Examination shows necrotic ulcers on the right leg, purpuric lesions on both legs, no arthritis but there is joint line tenderness at ankles, knees and wrists. Urine dipstick is normal, as is renal function. She has received no therapy. A nasal biopsy shows granulomatous infiltrates and she has a cANCA. She commences treatment with methotrexate and prednisone.

CASE 5
65-year-old male presented in July 1998 with a one month history of hemoptysis, breathlessness and pulmonary infiltrates and noted to have a blood stained discharge from his ear, arthritis, fever weight loss and haematuria with proteinuria and deteriorating renal function. His diagnosis of WG was established on renal and lung biopsy, and he was managed with cyclophosphamide, prednisone and (initially) plasma exchange. Unfortunately he went into renal failure and is now dialysis dependent, deaf, and awaiting transplantation.

On his routine clinic review in January 1999, he complains of constant fatigue, depression and feelings of utter hopelessness. He injured his right leg in the shopping mall two weeks previously and now has a full thickness ulcer on his lower leg. He has perforated eardrums with constant infections in the middle ear. His nasal passages feel blocked all the time, although there are no signs of active inflammation on ENT assessment. There are signs of early cataracts in both eyes. His blood pressure is 180/98. The rest of the examination is uninformative.

CASE 6
A 23-year-old man was diagnosed with WG by nasal biopsy three years prior to the current visit. At that time he had presented with epistaxis, nasal crusting, acute sensorineural hearing loss in the left ear, and subglottic stenosis, which required a tracheostomy. After therapy with cyclophosphamide and prednisone, his hearing improved somewhat. Over the ensuing two years was is taken off all therapy. He attends the clinic for an urgent appointment today, and tells you of a new skin rash present for the last three weeks: purpuric lesions on his legs. He also has noticed mouth ulcers, and he lifts his leg high when he walks. He has also had severe cramping abdominal pains with some bloody diarrhea. Examination reveals mouth ulcers, purpuric lesions on his legs, left foot drop (complete) with no sensory disturbance. The abdomen is diffusely tender, and sigmoidoscopy reveals friable bleeding mucosa, which is seen also on more extensive colonoscopy. A urinalysis with careful microscopic evaluation is normal.

CASE 7
A 36-year-old lady presents with a two week onset of sudden painless loss of vision in both eyes. She also reports chest pain, breathlessness on exertion, and cough with hemoptysis, and finds it difficult to take deep inspirations. She has recently developed mouth ulcers over the previous week. Examination reveals a temperature of 390C, inspiratory stridor, retinal hemorrhages and a left sided pleural effusion. There is a pericardial rub. Chest radiographs confirm the presence of a pleural effusion with large bilateral infiltrates, and an arterial blood gas reveals a pO2 of 50 mmHg on room air. The pCO2 is 38 mmHg. An ENT examination performed urgently reveals 90% subglottic narrowing with granulation tissue, a sample of which is diagnostic of WG. She requires a tracheostomy, ventilation, and immunosuppressive therapy. After extubation, she complains of a fullness in her vulvar region. Biopsy of a palpable nodule reveals necrotizing small vessel arteritis, with granulomatous features.

CASE 8
A 58-year-old man presents with a three month history of nasal crusting, epistaxis, sinusitis and general ill health. Examination reveals mouth ulcers, and ENT assessment confirms the presence of extensive nasal ulceration and inflamed mucosa. Biopsy from this tissue shows granulomatous inflammation. General examination is normal. A routine chest radiograph shows nodules in both lung fields, confirmed on CT scan to be multiple cavitating lesions consistent with WG. CT guided biopsy of a nodule is non-specific but no infection or malignancy is seen. He is ANCA negative. He is treated with methotrexate and prednisone.

CASE 9
A 14-year-old boy presents with a four month history of fatigue, arthralgia, myalgia, fevers (recorded as up to 39.50C) and headaches. He has lost 4 kg in weight, and also complains of nasal obstruction, epistaxis and nasal crusting. Urine contains 2+ protein, 3+ blood, and RBC casts. Urine culture is negative. His creatinine has risen from 1.2 mg/dl on admission to hospital three days earlier to 1.7 mg/dl. In the evaluation of his headaches, a CT scan is negative, but a lumbar puncture reveals a pleocytosis (80 WBCs, 50% polys, 50% lymphs) and CSF protein of 96 mg/dl. The CSF culture is negative.

CASE 10
A 71-year-old lady presented 3 years previously with a year-long history of recurrent nosebleeds, nasal obstruction, fatigue, weight loss of at least 8 kg, and sudden onset of hearing loss. Investigations confirmed sensorineural hearing loss, nasal tissue was diagnostic of WG and she was treated with cyclophosphamide and prednisone. Her condition subsequently improved, although she remains deaf and profoundly tired. On a follow-up visit today, (i.e., three years after her diagnosis), she complains of gross leg swelling over the last two months, and never before recorded. She is tired, has gross leg edema, a BP of 200/106 (previously normal), 4+ proteinuria, 3+ hematuria, with numerous RBC casts. Her creatinine is normal, but a 24 hour urine protein excretion is 4.5 g/24 hours. A renal biopsy shows crescentic GN. ÊÊÊ

Second Simulation Exercise

CASE 11
A 20-year-old man presents with palpable purpura on his lower extremities and buttocks. He also complains of joint pains, and on quick inspection has frank arthritis of his right ankle, left knee, and 3 or 4 small joints in the hands. He has been bothered for the past couple of weeks by post-prandial abdominal pain lasting 20-30 minutes, and has noted bright red blood in his stools several times. The entire syndrome was preceded by URI symptoms (sinus congestion & pain), which have persisted for more than 3 weeks now. His former pediatrician, whom he saw because he was home from college for the summer, had diagnosed him with Henoch-Schönlein purpura and given him some Tylenol for the joint pains. A urinalysis in the pediatrician’s office revealed hematuria but no red blood cell casts. No serum creatinine was measured.

The patient’s vital signs are stable, but he has lost 10 pounds over the past month. He has a combination of fresh and old blood in his nares. Both of his parotid glands are swollen and tender, and he says that he’s never had that before. He has the joint swelling mentioned above, and extensive, confluent purpura on the dependent portions of his skin. A urinalysis in your laboratory (which is pretty good most of the time, you think) shows 2+ protein and numerous RBC casts. The patient’s serum creatinine is 1.1 mg/dL.

CASE 12
A 41-year-old female truckdriver presents with complaints of hoarseness and shortness of breath. The hoarseness has been progressive for the past 3-4 months (perhaps longer), but she has been too busy to see a doctor. She thinks her energy has been a lot worse lately, but for a long time she has thought she was working too hard, smoking too much, and driving too fast. She finally walked into an emergency room because she noticed that she was coughing up small amounts of blood over the past few days.

On examination in the ER, she is febrile to 38.2 C, tachycardic (104 bpm), and tachypneic (20 respirations/minute), with stridorous breathing. Her O2 sat is 80%. She gets admitted because of a chest X-ray showing a large alveolar infiltrate on the right side. It is presumed that she has a community-acquired pneumonia, and she is treated with intravenous antibiotics.

Rheumatology is consulted after the 4th hospital day because she hurts all over, has not improved, and has an ESR of 110 mm/hr. You are immediately impressed by the stridorous nature of her breathing. She also has a nasal septal perforation and mild proptosis of the left eye (She insists that the latter is old, and presents old driver’s licenses to prove it). A repeat chest X-ray now shows a patchy left lower lobe infiltrate, while the infiltrate on the right is relatively unchanged. The patient is moved to the ICU for closer observation. You recommend a pulse of methylprednisolone while other investigations are pending.

Your suspicion of WG is confirmed when the ENT consultant finds severe subglottic stenosis on bronchoscopy, and a nasal biopsy shows necrotizing granulomatous inflammation, with scattered multi-nucleated giant cells. An ANCA test is negative by immunofluorescence. An MR of her orbits is unremarkable.

CASE 13 – REVIEW
The 41-year-old female truckdriver from Case 3 now returns for follow-up 11 weeks after discharge. She had been started on daily CYC (150 mg p.o. q day), prednisone 80 mg/day, and Bactrim DS i p.o. 3X/week. She feels great, but is now markedly cushingoid because she missed her previously-scheduled appointments and did not lower her prednisone as instructed. She hasn’t had her bloodwork checked since discharge either, but you are relieved to find that her WBC count is 11.4.

On examination, she has gained 30 lbs. since discharge and she is moderately hypertensive (140/96 mmHg). She has oral thrush, and has developed facial acne and mild hirsutism. She has grown impressive supraclavicular fat pads. There is no change in the mild left proptosis. The nasal septal perforation is clean, and there are no nasal crusts. Her voice is still a bit hoarse-sounding to you, but she says that this is normal for her. Her lungs are clear to auscultation and her skin is clear, aside from prominent abdominal striae.

You get her squeezed into ENT clinic, and the otolaryngologist reports fibrotic narrowing of her subglottic region but no active inflammation. In addition to her CBC, all of her bloodwork is within normal limits. You kindly admonish her about having her bloodwork checked every 2 weeks, outline a rapid reduction in steroids, and schedule her to see you again in 1 month.

CASE 14
A 28-year-old woman presented with a tonic-clonic seizure. She was found to have a serum Na+2 of 108 mEq/L. Workup reveals a 1.5 cm suprasellar mass and pan-sinusitis, but no evidence of bony destruction. She also has a thin-walled cavitary lesion in the left upper lobe, and several 1 cm nodules scattered throughout both lung fields. She received a presumptive diagnosis of sarcoidosis at an outside hospital (a bronchoscopic biopsy was negative, but her serum and CSF ACE levels were somewhat elevated). Her serum Na+2 improved after starting prednisone 60 mg/day. Three weeks later you are asked to see her semi-urgently because the patient really doesn’t feel well, and an ANCA test sent while she was in the hospital was positive in a titer of 1:640 (cytoplasmic pattern), and a PR-3 ELISA was strongly positive.

A careful history and physical examination does not reveal any more information, but her ESR is 114 mm/hr and her Na+2 has dipped from 132 to 118 since discharge. You discuss the possible implications of the patient’s serological tests with her, and convince her that pursuit of a tissue diagnosis is prudent at this time. She is admitted for a thoracoscopic lung biopsy, which she tolerates well. The biopsy shows areas of neutrophilic microabscesses, palisading histiocytes with necrotic centers, and pulmonary angiitis with fibrinoid necrosis.

CASE 15
A 54-year-old man is referred to you for management of his WG. He developed RPGN 7 years ago that was diagnosed as WG only in retrospect (after he had been on dialysis for a month), when it was recognized that he had had smouldering sinus, ear, and nose disease for years, leading to a Caldwell-Luc procedure, conductive hearing loss, and a nasal septal perforation. He is anuric. He tells you that his WG has not been active for 5 years, but he has been kept on 10 milligrams of prednisone a day during this time. He has recently developed glucose intolerance. He would like to stop the prednisone, because he is also tired of having “thin” skin. You agree, and design a steroid taper to take place over 2 months, beginning immediately.

When you see him at his 3-month follow-up visit, he is doing very well. A couple of weeks later, however, he calls to report that he has developed a red right eye. You see him urgently and immediately refer him to ophthalmology, who confirm that he has developed uveitis. His ESR has increased from 43 to 67 mm/hr. His ANCA has gone from negative at his first visit with you to positive at a titer of 1:80 (perinuclear pattern). ELISA testing reveals antibodies to PR-3, but no anti-MPO antibodies (both assays were negative previously). He has lost 5 pounds since stopping his prednisone.

CASE 16
A 54-year-old male newspaper publisher if referred to you the day before Thanksgiving because he had developed ischemic fingers and it is suspected that he has vasculitis. He became ill 6 weeks earlier, several days after receiving the influenza vaccine. He has been seen by physicians once or twice since getting sick, once in an emergency room and another time two days ago by the rheumatologist who referred him to you.

On examination, the patient is in considerable discomfort from his fingers, several of which are cyanotic, and says that he hurts everywhere. There is no digital gangrene, but he has numerous splinter hemorrhages bilaterally in his fingernails. Oddly, his lower extremities and toes are spared, but he does note some numbness on the outer portion of his left foot. His temperature is 37.8 C, and his heart rate 100/minute. His nasal mucosa is perhaps a little erythematous, but there is no crusting and no obvious inflammation. His lungs are clear, and on cardiac examination you hear what you’re pretty sure is a mid-systolic click, with a I/VI decrescendo murmur at the apex. Aside from the blue fingers, his skin exam is unremarkable. He has definite weakness of the right foot flexors that he had been unaware of, and he is unable to detect light touch on the lateral portion of the left foot.

He has a moderate leukocytosis (WBC 15K), and a normocytic anemia (Hct 33, MCV 81). His serum creatinine is 1.3 mg/dL. One week earlier in an outside emergency room his creatinine had been 0.8 mg/dL. His urinalysis has 1+ protein and microscopic hematuria, without RBC casts. The ESR is 80 mm/hr. An ANCA test sent by the local rheumatologist is strongly positive by immunofluorescence (an ELISA at your institution demonstrates an unequivocally positive test for antibodies to PR-3). A chest radiograph – and, subsequently, a chest CT – are normal. Blood cultures x 8 and a transesophageal echocardiogram are unremarkable except for mitral valve prolapse. A renal biopsy shows segmental, necrotizing GN with early crescent formation.

CASE 17
A 45-year-old attorney and mother of two is referred to you by the otolaryngologist for the possibility of an autoimmune condition. While on vacation, the patient had awakened with disabling dizziness and a humming sound in the left ear, followed within days by the onset of rapid hearing loss in that ear. By the time she reached the otolaryngologist 10 days later she was virtually deaf in the left ear and had become aware of an early decline in hearing on the right. Treatment with dexamethasone for 1 week had seemed to stabilize her hearing loss clinically, but serial audiologic testing documented no improvement in the left ear and the requirement for higher thresholds and worsening speech discrimination on the right.

While interviewing the patient, you learn that she has had a series of sinus infections over the previous 6 months. She has abundant nasal crusting. Otoscopy is unremarkable. She has one healing aphthous ulcer, but says that she has been prone to those since she was a child. Her ESR is now 48 mm/hr, but is was 90 when the otolaryngologist ordered the test 1 week ago. Antibodies to the 68 kD inner antigen are pending, but she has moderately positive antibodies to PR-3.

CASE 18
A 50-year-old basketball coach was diagnosed with WG 3 months ago when he presented with polyarthritis of the small joints of his hands, knees, and ankles, associated with a purpuric rash and hematuria with stable renal function. For several months prior to that he had been treated with antibiotics and myringotomies for refractory otitis media, worse on the right than the left. He was PR-3 positive. You started him on methotrexate, which he has now increased to 25 mg/week and tolerated well. He also took prednisone 60 mg/day at the beginning, but he has tapered his dose to 10 mg/day. He has an allergy to sulfa medications, so he takes dapsone 100 mg/day as PCP prophylaxis.

Since you last saw him one month ago, his energy has continued to improve but he still thinks he’s not back to his baseline. The joint pains have resolved completely, and there has been no sign of the skin rash since he began treatment. His hearing loss is stable, and he has not had any aural discharge since his first follow-up visit one month after beginning treatment. The only symptom he continues to complain of (he mentioned it vaguely at the time of his diagnosis) is chest pain that he gets when walking up the two flights of stairs to his office. You recall that he smokes at least two packs of cigarettes a day, and refer him to cardiology for further evaluation.

CASE 19
A 30-year-old woman has had WG for 19 months. She presented with pulmonary hemorrhage and rapidly progressive glomerulnephritis at that time, requiring intubation and a one week stay in the ICU. Before the diagnosis of WG was made, based on the finding of granulomatous inflammation on a thoracoscopic lung biopsy, she was treated with a course of plasmapheresis in addition to pulse methylprednisolone and daily CYC (administered intravenously while she was in the ICU, and given orally after extubation). She was treated with steroids for a total of 8 months, and CYC for 12. Since stopping the CYC she has not been on any treatment, and has become ANCA negative.

On a routine 3-month follow-up visit, she complains of stiffness in her hands in the morning, and a decrease in energy. Because she has fibromyalgia and a history of depression, her musculoskeletal complaints have always been difficult to read. On exam, however, she seems to have synovial bogginess in several PIP joints, and a warm, tender right wrist that she holds gingerly. Her urinalysis reveals hematuria without casts or proteinuria. Her last menstrual period ended two weeks ago. Her ESR has gone from 11 mm/hr at her last visit to 29 mm/hr, and she remains ANCA negative. You score her BVAS for WG as being in remission, but refer her to urology to evaluate her hematuria because you suspect CYC-mediated bladder damage. Three weeks later you are mildly astonished when the pathologist’s report of bladder biopsies describes necrotizing granulomatous inflammation of the bladder mucosa and small vessel vasculitis, admixed with mild fibrotic changes.

CASE 20
A 48-year-old man is admitted to the hospital with a DVT. This is his third DVT in the same leg in the last 2 years, and a hematological work-up detected a Factor V Leiden deficiency. He asks to see a rheumatologist while he’s in the hospital because he wonders whether his WG might be causing all of this. As it turns out, he was diagnosed with WG 8 years previously when he developed constitutional symptoms including weight loss, upper respiratory tract involvement, a productive cough, nodular pulmonary infiltrates and glomerulonephritis. At that time, he was cANCA positive (only immunofluorescence testing was available at the time), and he was treated with 15 months of CYC and prednisone. At the completion of therapy, his only residual organ damage was mild renal insufficiency (Cr 1.8 – 2.0 mg/dL).

Physical examination reveals a moderately obese man in no distress. His swollen leg has improved dramatically since he was admitted two days before your examination. He has bilateral pingueqolae of the eyes and a cauliflower ear on the left (he was a boxer in the Marine Corps). He has a xanthelasma on the lower left eyelid, and a smaller one on the right. His musculoskeletal examination is remarkable for prominent knuckle pads over the extensor surfaces of his fingers and a large bunion. There is some non-tender swelling of the left olecranon bursa, the etiology of which in not apparent. He has a well-healed midline scar in his epigastrium, the result of emergency surgery 20 years ago for a bleeding duodenal ulcer.

His routine admitting laboratories showed a normal CBC and serum chemistries, except for a serum Cr of 1.7 mg/dl. There is no proteinuria, and a chest X-ray is without abnormalities.

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