PULMONARY HEMORRHAGE COMPLICATING
PULMONARY ARTERIAL ANEURYSMS IN A
YOUNG FEMALE WITH BEHCET’S DISEASE
Roman Czubatyj M.D
Diego Vasquez M.D
Rheumatology Fellows 2
WSU/DMC/HFH
YOUR PATIENT
•
28 year old female, originally from Yemen, presents to the Emergency Room with
worsening shortness of breath and hemoptysis that started earlier that day.
•
Patient has a 6 year history of Behcet’s disease that was diagnosed by recurrent oral
ulcers, recurrent genital ulcers, arthritis, and recurrent panuveitis.
•
This is her third admission within 6 months with hemoptysis. She was intubated on her
second admission, only 2 weeks ago. She was treated with 1gm/day IV
methylprednisolone for 3 days, and improved. Discharged on 2mg/kg daily of prednisone
and 100mg daily of azathioprine.
•
She has been on prednisone and azathioprine off and on since 2006, but recently was
restarted after her first admission with hemoptysis
•
Patient denies any other symptoms except for shortness of breath and hemoptysis. She
states she has coughed up about ½ cup of blood.
HISTORIES
•
Past Medical History:
• Behcet’s Disease (diagnosed
2006)
• Recurrent oral and genital
ulcers, recurrent uveitis,
arthritis
•
• No rheumatologic disorders
•
• No alcohol use
•
• No illicit drug use
• Sexually active with her husband
Past surgical History
• None
Allergies:
• No Known Drug Allergies
Social History
• No tobacco use
• Complicated with Pulmonary
arterial aneurysms
•
Family History
• One healthy child
•
Home Medications
• Prednisone 2mg/kg/day
• Azathioprine 100mg Daily
PHYSICAL EXAM
• Vital Signs: Blood Pressure: 111/70 mmHg, Pulse: 92 bmp, Respirations 20 per minute
• Temperature: 37.1 C, Pulse Oximetry: 100% on 2 Liters by Nasal Cannula
• General Appearance : No Acute Distress, Patient sitting up in bed, Responds
appropriately to questions. Alert and Oriented to person, place and time
• HEENT: Pupils equally round and reactive, extra ocular muscle intact, external auditory
canal within normal limits, oropharynx demonstrates no lesions, no erythema, neck is
supple with no lymphadenopathy
• Respiratory: Inspection shows equal chest expansion, good respiratory effort, slight
crackles at her lung bases bilaterally
• Cardiovascular: No visible heaves on inspection, Regular rate and rhythm, no
murmurs, no rubs, no gallops. Peripheral pulses equal in upper and lower extremities
PHYSICAL EXAM
• Gastrointestinal : inspection reveals no scar, not distended, bowel sounds present in all
four quadrants, no tenderness, no rebound, no guarding
• Genitourinary: No lesions present, normal female
• Musculoskeletal: no deformities present, all joints have good range of motion, no
tenderness, synovitis, erythema. Good muscle tone throughout, 5/5 strength in upper and
lower extremities
• Integumentary: No rashes present, no lesions
• Neurological: Cranial Nerves II-XII intact, no gross deficits
• Psychiatric: Cooperative
LABORATORY VALUES
•
White Blood Cells: 6.8 K/ul
•
Sodium 137 mmol/L
•
Potassium: 3.9 mmol/L
•
Chloride: 102 mmol/L
•
Carbon Dioxide: 31 mmol/L
•
BUN: 15 mg/dL
•
Creatinine: 0.46 mg/dL
•
Hematocrit: 33.4%
•
Glucose: 95 mg/dL
•
MCV: 89.6 fl
•
Calcium: 8.7 mg/dL
•
MCH 29.9 pg
•
Magnesium: 1.8 mg/dL
•
MCHC 33.4 g/dL
•
Prothrombin time: 13.7 sec
•
RDW 18.5%
•
INR: 1.04
•
Platelets: 333 K/uL
•
Partial thromboplastin time: 24 sec
•
Sed Rate, Westergren: 11 mm/Hr
•
C-Reactive Protein: <0.3 mg/dL
•
•
65% Neutrophils
•
24% Lymphocytes
•
10% Monocytes
Hemoglobin: 11.1 g/dL
•
Baseline: 12.8 g/dL
IMAGING
Multifocal airspace disease which appears to be more confluent within the left mid-lung. Given the clinical
history, underlying alveolar hemorrhage is again favored.
CT IMPRESSIONS
•
1. Diffuse patchy lung opacities particularly in the left lower lobe consistent with
hemorrhage in the setting of hemoptysis. Although overall pattern of lung
opacification has improved from previous CT, the pattern of resolution and
recurrence by interval chest x-rays suggests that this hemorrhage is new.
•
2. Approximately 1 cm pulmonary arterial aneurysm versus pseudoaneurysm
adjacent to the left hilum is decreased in size from prior examination. Separate
aneurysms described on prior CTA examination have significantly decreased or
resolved.
6 months ago
PREVIOUS CT SCAN
CLICK HERE TO SKIP
CT IMPRESSION
• 1. Numerous bilateral pulmonary artery aneurysm is as detailed
above, the largest in the left upper lobe, compatible with history
of Behcet's disease.
• 2. Thrombus is noted within most of the aneurysms with
occlusion of several right lower lobe segmental arteries.
• 3. Peripheral, nodular opacities in the right lower lobe may
represent small areas of infarct.
• 4. Ground glass opacity in the left upper lobe and bilateral lower
lobes could represent atelectatic change, however, given history
of hemoptysis, these also could represent areas of hemorrhage.
MANAGEMENT
•
Patient was admitted and Rheumatology was consulted
•
Rheumatology recommended starting methylprednisolone IV 1gm daily for 3 days
•
Discussions with the patient regarding treatment options occurred at her last admission
• She is a young female who desires to have more children
• Safety and information about treatment options were shared with the patient
• She agreed that trying an anti-TNF would be best for her
• TB test negative
•
After her 3 days of IV pulse steroids patient had resolution of her initial symptoms
•
She was started on Infliximab 5mg/kg.
•
She received her loading dose of infliximab at 0, 2, and 6 weeks
•
Started on regular treatments at 8 week intervals
UPDATE (1 YEAR)
•
Patient continues to receive IV infusions of infliximab at 5mg/kg every 8 weeks
•
Also taking azathioprine 100mg daily
•
She has been symptom-free since her last admission (16 months ago)
•
She has reported no side effects from the medication.
DISCUSSION
• Pulmonary arterial aneurysms, as part of vascular complications in BD are
not as uncommon as previously thought. The reported prevalence is up to
30%, and these represent the most frequently fatal complication in BD
occurring almost exclusively in young males 4.
• Even though the etiology of BD is currently unknown, tumor necrosis factoralpha (TNFα) has been involved in the pathogenesis of this disease 5, being
found locally and systemically elevated in BD 6. Although the use of
Infliximab to treat pulmonary aneurysms is increasing, there are no
randomized controlled trials to confirm the reported findings.
•
Infliximab is a chimeric monoclonal antibody specific for human TNFα, and
administered by intravenous infusion. Infliximab is dosed by weight and is started
at 3 to 5 mg/Kg, and titrated up to 8 mg/Kg. It is infused every 8 weeks after the
initial induction is completed (0, 2 and 6 weeks).
•
The response to Infliximab in severe vascular BD is impressive. There are
multiple case reports 7,8,9 that describe its use and quick resolution of the
aneurysms as well as improvement in inflammatory markers and other disease
manifestations.
•
This is another case of refractory ocular and mucocutaneous BD complicated
with pulmonary arterial aneurysms, that although responded initially to
azathioprine and prednisone (decrease in aneurysm size) had recurrence of
hemoptysis, skin and mucosal disease, which lead to initiation of Infliximab.
• Currently, she is in remission for over a year with regularly scheduled (every
8 weeks) infusions of infliximab at a dose of 5mg/kg, and also azathioprine
100mg daily.
• The peculiarity of our case is the gender of the patient. Being a young
female that desires further pregnancies therapeutic options were limited, as
cyclosporine and other immunosuppresants were eliminated as options.
• Furthermore, we believe that as the ethnicity and prevalence is changing
with time, the disease characteristics by gender may also be changing.
CONCLUSION
• Behcet’s Disease (BD) is a rare, chronic disorder that is being
recognized in more ethnicities than before.
• Treatment of the manifestation of this disease can be difficult and
should be tailored directly to the patient. Prednisone, colchicine and
azathioprine have shown benefit in treating this disorder.
• Recently TNF inhibitors, Etanercept and Infliximab, have been used.
Etanercept has some clinical data for the use in mucocutaneous
disease, but currently there are no randomized controlled trials for
Infliximab.
• Currently, there are very few studies done with TNF inhibitors and BD.
Other case reports have been published, but more research is
needed.
REFERENCES
•
Hamzaoui K, Berraies A, Kaabachi W, Ammar J, Hamzaoui A. Pulmonary manifestations in Behcet Disease:
impaired natural killer cells activity. Multidiscip Respir Med. 2013 Apr 4;8(1):29..
•
Seyahi E, Melikoglu M, Akman C, Hamuryudan V, Ozer H, Hatemi G, Yurdakul S, Tuzun H, Oz B, Yazici H.
Pulmonary artery involvement and associated lung disease in Behçet disease: a series of 47 patients. Medicine
(Baltimore). 2012 Jan;91(1):35-48.
•
Bilgin G, Sungur G, Kucukterzi V. Systemic and pulmonary screening of patients with Behçet's disease during
periodic follow-up. Respir Med. 2013 Mar;107(3):466-71. doi: 10.1016/j.rmed.2012.04.005. Epub 2012 Dec 21.
•
Yazici H, Esen F. Mortality in Behçet's syndrome. Clin Exp Rheumatol 2008;26(5 Suppl 51):S138-40
•
Alpsoy E, Akman A. Behçet's disease: an algorithmic approach to its treatment. Arch Dermatol Res
2009;301(10):693-702
•
Turan B, Pfister K, Diener PA, Hell M, Möller B, Boyvat A, Ergin S, Villiger PM. Soluble tumour necrosis factor
receptors sTNFR1 and sTNFR2 are produced at sites of inflammation and are markers of arthritis activity in
Behçet's disease. Scand J Rheumatol 2008;37:135-41
•
Schreiber BE, Noor N, Juli CF, Haskard DO. Resolution of Behçet's syndrome associated pulmonary arterial
aneurysms with infliximab. Semin Arthritis Rheum. 2011 Dec;41(3):482-7.
•
Adler S, Baumgartner I, Villiger PM. Behçet's disease: successful treatment with infliximab in 7 patients with severe
vascular manifestations. A retrospective analysis. Arthritis Care Res (Hoboken). 2012 Apr;64(4):607 -11.
•
Arida A, Fragiadaki K, Giavri E, Sfikakis PP. Anti-TNF agents for Behçet's disease: analysis of published data on
369 patients. Semin Arthritis Rheum. 2011 Aug;41(1):61-70.