Red Eyes in Rheumatology
Dr. Dave Cescon
PGY3 Internal Medicine October 2007
Outline
• Case
• Learning objectives
• Topic review
• Key Points
Case 1 Red Eyes: What‟s the Cause?
• 48F, previously healthy • Referred by ophthalmology
– RFR: Scleritis
What‟s Scleritis?
• Inflammation of sclera with engorgement of scleral vessels
Case
• Symptoms of painful, red eyes began summer 2007, shortly following “flulike illness” • Initially diagosed as acute angle glaucoma, treated with iridotomy
Course of Illness
• Worsening pain, photosensitivity, headaches • Prescribed topic & oral NSAIDS, steroid drops without improvement • Sept 14: bilateral nodular anterior scleritis + posterior involvement • Malaise, myalgias persisted
Course of Illness (con‟t)
• Developed other extra-ocular symptoms
– Intermittent, severe pleuritic chest pain
– Painful swelling R wrist (resolved with ibuprofen)
– R hand paraesthesias (ulnar distribution) – Drenching night sweats – Non-pruritic papular rash
Pertinent Negatives
•No:
– Fever
– Photosensitivity rash, alopecia, nasal/oral ulcers
– Arthritis, AM stiffness
– Respiratory/sinus symptoms
– Sicca – Raynauds – Cardiac, GI symptoms – Sick contacts, travel
History (Con‟t)
• No family history
• Premature menopause, no relevant medical history • 1 PPD smoker • Occ EtOH, no IVDU
Physical Findings
• Mildly unwell
• Bilateral scleritis with nodularity
• ~6 erythematous papules (~4mm)
• No other abnormalities
Investigations
• MRI head
– No intracranial pathology
• CT Chest
– Emphysema – Small pleural effusion – Non-specific parenchymal densities ?atelectasis – No PE, no adenopathy
Laboratory Investigations
• CBC:
– Hgb 119 – Plts 406 – WBC 12: N 7.7, Eos 1.5
• Lytes, Cr, Liver profile, Coags:
Normal
• ESR 85, CRP 105 • Urinalysis: Normal
Serology
• RF, ANA, ANCA, ACA: Negative
• Complements: N/ • Hepatitis, VDRL: Negative • Cryoglobulins: Negative • ACE level: Normal
Pathology
• Eye
– Chronic granulomatous inflammation – No vasculitis – Fungal stain negative – ?ZN stain abnormality – Otherwise consistent with sarcoid
– Not typical of RA
Pathology
•Skin
– Granulomatous dermatitis
• DDx: Interstitial granulomatous dermatitis with arthritis, granuloma annulare, unusual infection • Not characteristic of sarcoidosis • ZN, silver stains pending
– Immunofluorescence negative
What is the diagnosis?
What is the treatment?
Objectives
• Differentiate causes of red eyes • Review scleritis subtypes • Understand systemic disease associations, and appropriate workup • Review approach to treatment of scleritis • Solve the case
Other Causes of Red Eyes
• Conjunctivitis
• Episcleritis
• Anterior uveitis (iritis)
• Acute angleclosure glaucoma
• Corneal ulceration
Scleritis Subtypes
• Anterior Scleritis (90%)
– Diffuse
– Nodular – Necrotizing
• With inflammation
• Without inflammation (scleromalacia perforans)
• Posterior Scleritis
Posterior Scleritis
Scleritis and Systemic Diseases
• ~ 50% are manifestations of systemic disease
• Most are rheumatologic conditions
• Estimated incidence in RA: 1 – 6%
Table 1 Frequency of systemic disease among patients with scleritis
Scleral Inflammation
• Zonal necrotizing granulomatous inflammation in a patient with rheumatoid arthritis (A)
• Diffuse nongranulomatous inflammation in a patient with „idiopathic scleritis‟ (B)
Scleritis vs Episcleritis
Scleritis
• Red Eye
• PAIN • Photophobia • Purplish sclera • Edema or thinning of sclera
Episcleritis
• Red eye • Not painful • Less • None • No scleral changes present • Resolves with phenylephrine
• No change with phenylephrine
Episcleritis and Systemic Diseases
• ~1/3 (in tertiary centre) associated with rheumatologic disease or infection
– Rheumatoid arthritis 11% – IBD 8%
– – – – –
Vasculitis 5% SLE 3% Other rheum: 3% HZV: 3% Lyme 3%
Treatment of Scleritis
• Always requires systemic therapy with NSAIDS or corticosteroids
• 2/3 require high dose steroids +/immunosuppressive
Diffuse and Nodular
• Many respond to NSAIDs alone
– Indomethacin preferred
• More severe cases, NSAID failures usually respond to high dose steroids (1mg/kg)
Necrotizing or Posterior
• Higher frequency of complications • More aggressive therapy required:
– High dose steroids (1mg/kg)
– Pulse solumedrol for impending ocular complications
Ongoing Therapy
• Slow prednisone taper over 6-12 months • Addition of immunosuppressive therapy if persistent inflammation after 2-3 weeks
– Oral cyclophosphamide – MTX, Azathioprine, MMF, cyclosporin
• Mixed evidence for TNF agents
Outcomes
• Rapid response (1-2 wks) to therapy expected • Some permanent visual loss in 1085% • Glaucoma, cataracts in up to 20%
– especially nodular subtype
• Ulcerative keratitis, corneal melt rare
Back to the Case
• Diagnosis uncertain
– ?Sarcoid – ?Infectious – ?Vasculitis or RA in evolution – Integration of path results
• Responding well to prednisone
• Await scleral biopsy path review
Summary
• Scleritis is vision threatening and must be distinguished from other causes of red eye • A systemic disorder is present in ~50%
– History, physical, routine labs, serology, U/A, CXR comprise usual workup
• Aggressive therapy warranted, especially in necrotizing, posterior variants
Part II
More to worry about than red eyes?
Case 2
• 18F • Juvenile RF+ polyarticular arthritis x 5y • Persistently active, destructive disease despite prednisone, multiple DMARDs • Currently on prednisone, leflunomide, etanercept, piroxicam
• Uses marijuana daily, with effective pain relief
Any concerns with her “treatment”?
Objectives
• Highlight a potential complication of marijuana use
• Review patterns of medicinal marijuana use • Understand Health Canada‟s marijuana access program
Discussion
• Invasive aspergillosis (IA)
– Clinical manifestations – Risk factors
• Marijuana and aspergillosis
• Marijuana and arthritis
Invasive Aspergillosis
• A. fumigatus
– Ubiquitous filamentous fungus (mould) found worldwide (water, soil, vegetation)
• Sites of invasive disease:
– Pulmonary – Sinus – Endophthalmitis – CNS – Cutaneous
Risk Factors for IA
• Prolonged, profound neutropenia (>3 weeks) – Most common in hematologic malignancies, SCT • • • • • • • Systemic corticosteroids Chronic lung disease Anti TNF agents Marijuana use Solid organ transplantation Advanced AIDS Primary immunodeficiency
IA Without Neutropenia
• Series of 88 cases over 6 years at tertiary institution (France) • 41% non-neutropenic
• 22% steroids only risk factor
– 6 cases rheumatic disease
• Low steroid doses (<15 mg prednisone/d) sufficient for IA when administered continuously
Anti TNF and IA
• Invasive Pulmonary Aspergillosis Associated with Infliximab Therapy
• Through 2002 FDA AERS:
– Infliximab 29 (12.4/100 000) – Etanercept 10 (8.8/100 000) – ~1/10 of TB rate
Marijuana and Aspergillosis
• Recognized association
– Solid organ transplant, AIDS, chronic granulomatous disease, BMT, leukemia
• Mechanism:
– Contamination with fungal spores
– Modulation of local pulmonary immune function
Marijuana and Rheumatic Disease
• 2737 B.C., mystical emperor Shen Nung
– Marijuana “undoes rheumatism”
– Prescribed for the treatment of gout, rheumatism, malaria, poor memory
Marijuana Use
• Telephone survey of 2508 Ontarians
– 2% medical reasons
• 41/49 for pain/nausea
– 7% non-medical reasons
• UK survey 1998 - 2002
– 2696 pts with chronic conditions
• 155/947 used for arthritis • RA patients: 72% “much better”, 28% “little better” • 2/3 of users had previously used recreationally
Anti-inflammatory Properties?
• Cannabidiol in mouse collageninduced arthritis
– Dose-dependent suppressive action on the clinical arthritis and joint damage – Suppression of TNF, IFN, lymphocyte proliferation
Medicinal Marijuana in Canada
• Available through Health Canada
• Marijuana Medical Access Regulations
– Qualifying conditions include “Severe Arthritis” with “Severe Pain” – Conventional treatment(s) have been tried or considered, and have been found to be ineffective or medically inappropriate for the treatment of the applicant
Medicinal Marijuana in Canada
• Cultivated in Flin Flon, Manitoba
– Tested for microbial contamination and irradiated
• Many users of medicinal marijuana obtain supply through street sources
Marijuana Medical Access Statistics
• Canada
– 1816 patients, supported by 1063 physicians
• Ontario
– 807 patients, supported by 470 physicians
Key Points
• Inhalation of marijuana via smoking is a risk factor for pulmonary aspergillosis • Immunosuppressed patients (including low dose steroids, TNF inhibitors) are at increased risk of IA • Patients smoke pot!
– Should be counselled – Safer supply might be accessible
• Consider IA in patients with respiratory illness
Thank you
Questions?