Back in 2011 the company my wife worked for offered access to Best Doctors® as part of the company health benefits plan. I used this opportunity to try the service out in hopes it might magically determine a cure for my health problems stemming from Pulmonary Sarcoidosis. Unfortunately, nothing new came of this process as the report I received basically reiterated what my own doctors were saying. That’s good in that it gave me further comfort that I was getting appropriate care but there was a part of me left disappointed as I kept hoping to get fixed and be back to normal. Anyway, despite its limited value to me personally I think it’s interesting to see the report I received since it gives a pretty good summary of what my history with Sarcoidosis had been up to that point.
Best Doctors® Report – September 2011
The following consultation report of The Patient Age 39 is based on a review of the submitted material. I reviewed all the material including the clinical summary, report of the pulmonary test, chest X-ray reports and images and chest CT scan. The Patient seeks an opinion on the management of his sarcoidosis.
History of Present Illness:
The Patient was a healthy man in his early 30’s, when in 2002 he developed profound fatigue, arthralgias and eye pain/dryness. He was evaluated and a diagnosis of mild uveitis. He was treated with steroid eye drops and/or artificial tears with resolution of pain. Over time, symptoms improved, but mild fatigue continued. Subsequent ophthalmologic evaluation did not confirm the original impression.
In the spring of 2008, he developed dyspnea. There was no cough/wheeze, fever, chills or night sweats. He was a nonsmoker and worked as an office geologist. He had no recent travel, infectious contacts or occupational exposures.
In August 2008, plain films revealed bilateral hilar lymphadenopathy. A chest CT revealed enlarged mediastinal and hilar lymph nodes. There were no parenchymal changes noted.
The Patient was referred to a pulmonologist. Physical exam was without abnormal findings. The pulmonologist noted that on high resolution cuts, there did appear to be a micronodular pattern in a bronchovascular distribution. Pulmonary function testing revealed mild fixed airflow obstruction with preservation of lung volumes and diffusion capacity (see below).
The impression was of sarcoidosis. It was felt unclear if the airway obstruction was due to the sarcoidosis vs. a concomitant asthma. A bronchoscopy was planned. A trial of Budesonide/Formoterol (Symbicort) 2 puffs bid was prescribed. The transbronchial biopsy revealed one non-necrotizing microgranuloma. Fine needle aspiration of the mediastinal lymph nodes demonstrated non-necrotizing granulomata. Cultures werenegative. The dyspnea responded to the Symbicort. Celecoxib was prescribed for the arthralgias, but was not taken.
In November 2008, The Patient was evaluated by an internal medicine physician who questioned whether eye pain could be the result of extraocular muscle involvement by sarcoidosis. During the year 2009, The Patient reports he continued to use the Symbicort and another steroid inhaler. No medical records are available from that year.
In January 2010, there was a complete clinical and radiographic resolution of the sarcoidosis. The inhalers were discontinued. Expectant management was decided upon. By the spring/summer of 2010, fatigue, cough, dyspnea, arthralgias and eye pain had recurred. Pulmonary function testing demonstrated mild airflow obstruction and a decreased vital capacity. Plain films revealed multiple pulmonary nodules bilaterally. The patient was now considered to have stage 2 disease. Prednisone therapy was initiated at 50 mg daily, for at least one month. At the end of August 2010, PFT’s revealed normalization of the previously observed airflow obstruction on the prednisone. The Patient experienced adverse effects from the high dose steroids including severe mood changes with some violent behavior, heat intolerance and headaches. His dose was halved, and then tapered slowly with less side effects. By December 2010, The Patient’s dyspnea had improved, and prednisone was tapered to 5 mg.
In early 2011, The Patient began developing dyspnea on exertion. A recent echocardiogram had been within normal limits. Chronic, non-productive cough became somewhat worse. He was evaluated again by the internal medicine physician. Symbicort was restarted. Further cardiac evaluation was recommended.
An ECG revealed an incomplete intraventricular conduction delay with a left bundle pattern (seen in 2008). A recent ECG also revealed a new left anterior hemiblock. An exercise tolerance test revealed no evidence of ischemia.
In May, The Patient was evaluated by an ophthalmologist. He reported pain behind his eyes and photosensitivity. An ophthalmologic exam and fluorescein angiogram revealed no evidence of sarcoid related abnormalities. In June, a chest X-ray revealed moderately prominent reticular nodular interstitial markings in the mid and upper lung zones bilaterally. Spirometry revealed a fall in vital capacity, although absolute lung volumes were still above normal. The FEV1/ FVC was 4.6/6.46 (72%) compared to 4.96/6.91(72%) in December 2010.
The Patient met with the pulmonologist. Fatigue, arthralgias and eye discomfort were reported along with increased dyspnea. The impression was of stage 2 disease. The pulmonologist recommended reinitiating prednisone therapy. The Patient deferred, explaining that he felt that prednisone only suppressed acute deterioration, but fluctuations in sarcoidosis course occurred independently.
Steroid sparing agents were discussed. (Methotrexate has been cited in other office notes.) The pulmonologist added the caveats that these agents would not obviate the need for prednisone and that they could take at least 6 months to take effect. The Patient reports that plain films and spirometry in September were identical to results in June.
The Patient feels that there is a correlation between flares of his disease with any physical exertion. He has been referred to a rheumatologist for further evaluation of arthralgias and chronic back pain. A recent orthopedic evaluation for his back pain diagnosed myofascial pain and recommended trigger point injections (perhaps with steroids?) Cervical/thoracic spine imaging over time has revealed degenerative disc disease.
Past Medical/Surgical History:
Sarcoidosis as above
The Patient is married with two children. He is a trained geologist. He has never
smoked (the history states no occupational exposure yet the patient is a geologist)
No history of sarcoidosis
Exam by internal medicine physician 03/11: No significant abnormalities
Exam by ophthalmologist 06/11: No evidence of active uveitis
08/28: Normal studies
10/08: Normal studies
12/08: No abnormalities on rheumatology work up. Mild non-specific increase in IgA
03/11: Lyte’s normal
08/13/08: Chest CT (reviewed): enlarged mediastinal hilar and paratracheal lymph nodes. Normal lung fields.
12/02/08: PA and lateral CXR: Hilar and mediastinal LN
01/26/09: CT of the brain and orbits w contrast: No significant abnormalities
01/09/10: Cervical spine MRI: Degenerative disc disease at several levels
07/20/09: PA and lateral CXR (reviewed): Resolved abnormalities
01/25/10: PA and lateral CXR: paratracheal lymphadenopathy
08/10/10: PA and lateral CXR: More prominent interstitial markings and stable mediastinal abnormalities.
08/27/10: PA and lateral CXR (reviewed): Mild Interstitial changes and mediastinal LN.
12/13/10: PA and lateral CXR: (reviewed) Resolved interstitial changes but increased paratracheal stripe.
05/11/11: Florescein angiography: No evidence for vasculitis. Atrphic RPE changes.
06/13/11: PA and lateral CXR (reviewed): Significant increase in micronodular (miliary) changes
08/15/11: Thoracolumbar bone imaging with SPECT: Mild degenerative changes of dubious significancePFT’s:
08/18/08: FVC 6.36L (112%), FEV1 4.34L (93%), Ratio 68% No significant Bd response but improved flows at low lung volumes. Normal lung volumes (TLC 106%) and Diffusing capacity (116%). Results indicate mild airflow obstruction.
01/25/10: FVC 7.07L (125%), FEV1 5.09L(110%) Ratio 72%. DL 125%
08/10/10:FVC, 6.71, (119), 4.84 (105) Ratio 72%
08/27/10: FVC 6.77L (121), FEV1 5.14 (111) Ratio 75%
12/13/10:FVC 6.91L (123) FEV1 4.61L (108) Ratio 71%
06/10: FEV1 4.6/FVC 6.46 (72%) CXR – reticulonodular disease
09/17/10: Within normal range
03/25/11: Left axis deviation
Treadmill Stress Testing:
04/07/11: Good exercise capacity with no significant abnormalities
08/28/08: BAL of RLL: Lymphs 22%, Macrophages 725 (increased lymphocytes counts)
08/28/08: Transbronchial biopsies: Single non-caseating granuloma reviewed and confirmed by University Health Network in Toronto
08/28/08: FNA of mediastinal lymph node: Non necrotizing granulomatous inflammation (reviewed and confirmed by University Health Network in Toronto)
Assessment and Plan:
The Patient is a 39 year-old man with symptoms of fatigue, eye pain and arthralgias dating back to 2002. He developed dyspnea in 2008, and was diagnosed with sarcoidosis by biopsy. In the summer of 2010, there was clinical, radiographic and spirometric deterioration of disease, and prednisone at 50 mg was started. Symptoms and PFT’s improved, but this high dose was poorly tolerated. The dose was halved and then tapered. These lower doses were tolerated.
1. Please confirm The Patient’s diagnosis and assign a stage. In your discussion, please address if the stage of disease has changed over time.
The patient has sarcoidosis progressing from stage I to stage II over 3 years or more years. The disease has responded to high dose prednisone and has relapsed radiographically and by PFTs since tapering steroids. The airflow obstruction is due to enlargement of central lymph nodes and involvement of the smaller airways with sarcoidosis. There is no evidence in the history of any other pulmonary condition including occupational exposure to rock dust and silica.
2. In layman’s terms, please discuss sarcoidosis. Explain what it is, the underlying etiology, the risk factors for development, the demographics, the diagnostic criteria, the clinical presentation, the natural history, and associated complications over time.
The patient is referred to the reference #3. In brief sarcoidosis is a disease of unknown cause with genetic, host and environmental risk factors. Family clusters have been described. It is likely that an environmental agent is in part a cause perhaps related to a tuberculosis protein (see ref #1). However no definite factor
has been identified. The patient fulfills clinical and diagnostic criteria for sarcoidosis. Complications include lung disease, skin, and eye resulting over the long term with scar. Less commonly joint, heart and brain/spinal cord are involved (see ref #1 & 2). Calcium levels in blood and urine may be elevated (not given in submitted records). Diagnosis is made by clinical presentation confirmed by characteristic biopsy of tissues showing granulomas which are ‘factories’ of inflammatory chemicals and growth factors. The disease is thought in involve the acquired and innate immune systems with oligoclonal (a family of cells expanded from a common original cell) T lymphocytes as effector cells against the unknown protein or part of protein (see reference 1&2).
3. Please outline a comprehensive medical treatment plan for The Patient including (1) how you would judge when active therapy was warranted and (2) how you would introduce medications over time. High dose steroids have been poorly tolerated.
As The Patient’s disease has relapsed over 3 years it is unlikely to resolve any time soon and therefore steroids are indicated. I would start with 40mg/day and carefully drop by 10mg each month to around 10mg/day. The disease is usually well controlled with low dose steroids around 10-15mg/day. Although it is true that steroids control symptoms of sarcoidosis and improve well-being steroids do not alter long term course of the disease. The patient also responded to symbicort and this should be restarted. A combination of low dose steroid plus symbicort may be sufficient to control the disease.
A controlled trial has shown early treatment of stage II with 3 months steroids followed by high dose inhaled budesonide have improved PFT’s after 5 years. (ref#4). The improvement resulting from this treatment are however modest. Second line agents such as methotrexate, or plaquinal are used if the dose of steroids required to control the disease is too high (i.e. steroid sparing). There is no convincing evidence that more powerful immune suppression agents including infliximab are more effective (see ref #1).
4. Please discuss when, if ever, you would recommend PCP prophylaxis and the recommended dosage.
Not at this point but if the patient embarks on a long term course of steroids then PCP prophylaxis may be considered. (I seldom put my patients on this therapy). If the patient has latent TB, TB prophylaxis can be considered with long term steroid therapy.
5. The Patient is concerned that physical activity exacerbates his disease and possibly contributes to flares. Please address these concerns.
No, physical activity does not exacerbate his disease and does not contribute to flares. What the patient with active sarcoidosis generally feels is the fatigue and shortness of breath during exercise. Sarcoidosis can also affect the muscles (as can high dose steroids). On the contrary inactivity is harmful leading to loss of
cardiac and muscle function, stamina and endurance. The patient has had a normal cardiac work-up and therefore should undergo an exercise program when stabilized on medication.
6. Please discuss if you feel The Patient’s ophthalmologic symptoms could be related to his sarcoidosis. Referral to which type of subspecialist would be appropriate in this setting?
I am not in a position to comment on the eye condition. Sarcoidosis is known to affect all parts of the eye and cause uveitis. It appears that the patient requires regular eye check-ups for sarcoidosis.
7. Please discuss how you would address The Patient’s back pain and arthralgias.
Athralgias and fatigue are due to the systemic effects of active sarcoidosis that can also affect the joints. Back pain is common in those without sarcoidosis and is likely due to postural or use problems. Back strengthening though rehabilitation can address this problem. Regular non-steroid anti-inflammatory medications such as naproxen, diclofenac or indomethacin may be tried.
8. Please discuss if you feel The Patient’s mild cardiac conduction disease is related to the sarcoidosis.
Although the patient does not show any cardiac symptoms, it is possible. Sarcoidosis affects the heart more commonly than is diagnosed (ref #1 & 2). The diagnosis of cardiac sarcoidosis is difficult and newer techniques such as PET scan and contrast cardiac MRI have been reported to be highly sensitive (see references #1 and 2)
9. How should The Patient be followed over time? He feels that his current providers tend to focus on one system only.
Sarcoidosis is a systemic disease. However pulmonary specialists who regularly see patients with sarcoidosis and eye physicians should be able to follow for most problems. Sarcoidosis is not generally the specialty of GPs so unfortunately a patient’s care tends to be fragmented. Regular follow up is required with PFTs
used to monitor response to therapy and progress over time. A chest X-ray is more useful at this stage than CT scans as it is easier to compare one study to another.
10. Please discuss The Patient’s prognosis.
Sarcoidosis has a good prognosis. Overall progression to an advanced stage occurs in 20% and the disease resolves in up to 50% over 3 years. Stage 2 disease eventually and slowly clears in about 40% of cases. Only about 5% die from the disease (usually fibrosis or scaring of the lungs).
11. If not addressed by the questions above, please provide any further recommendations that you believe will aid in understanding this patient’s findings or in guiding future therapeutic decisions.
Side effects seem to be a problem with treatment and this is a common complaint of patients. However the disease seems to be entering a chronic phase and it is my opinion that maintenance low dose steroid program will be necessary to control the disease.
12. Please provide scientific references that may be helpful to the treating physicians and the patient, and/or that lend support to your recommendations.
1) Morganthau A, Iannuzzi M. Recent advances in sarcoidosis Chest 2011;139;174-182
2) Iannuzzi MC, Rybicki Ba, Teirstein AS. Sarcoidosis. N Engl J Med. 2007;357:2153-2165.
3) Pubmed Health by the National Institutes of Health http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001140/
4) Anne Pietinalho, Pentti Tukiainen, et al Early Treatment of Stage II Sarcoidosis Improves 5-Year Pulmonary Function. Chest January 2002 121:1 24-31 Respectfully submitted, Edward Eden MD