Chlamydia-induced

Reactive ArthritisTreatment Options and Remission

Camille Renee

January 26, 2015

Dr. F.M.

RHM2 4111

Outline

Approach to Research

P.I.C.O. Summary

What is Reactive Arthritis?

Current Treatment Plan

Treatment-based Case Report

Remission

Remission-based Case Control Study

Questions for Future Research

Approach to Research

Approach to Research

Approach to Research

Approach to Research

Source: Duke Library

1

2

Source: JaypeeJournals.com

P.I.C.O.

Patient Problem: ◦ Joint pain

◦ Conjunctivitis

◦ Symptoms occur weeks after treatment of Chlamydia trachomatis

Intervention: ◦ Serology (HLA-B27)

◦ Cytoplasmic inclusions on histology

◦ Antibiotics

◦ Methotrexate

P.I.C.O.

Comparison:

◦ TNF-α inhibitors i.e. Etanercept

Outcome:

◦ Pain relief

◦ Inflammation reduced

◦ Resolution

Reactive Arthritis

‘Reiter’s Syndrome’ (classic triad)1) Urethritis/Cervicitis

2) Conjunctivitis

3) Arthritis

Generally associated with HLA-B27 on serology

Post-venereal type is particularly associated with Chlamydia trachomatis infections

‘Can’t See, Can’t Pee, Can’t Climb a Tree.’

Toronto Notes, 2014

Reactive Arthritis –

Post-enteric Type

Chlamydia Trachomatis• Most prevalent sexually

transmitted bacterial pathogen

• May cause:

• Reactive arthritis (Reiter’s

syndrome)

• Follicular conjunctivitis

• Nongonococcal urethritis

(NGU)

• Pelvic inflammatory

disease (PID)

• 3 million new C. trachomatis

infections occur each year in the

United StatesSource: Le, T. First aid 2014

Only 4% of these

cases lead to

inflammatory arthritis

C. Trachomatis - Replication

Source: Carter, J.D. Int J Clin Rheumtol. 2011

C. Trachomatis - Histology

Source: Carter, J.D. Int J Clin Rheumtol. 2011

Traditional Treatments

Toronto Notes, 2014

Etanercept – Case Report

Successful use of Etanerceptfor the treatment of Reiter’s syndrome: a case report and review of the literature (Edrees, A., 2011)

33 year old male with Chlamydia-induced reactive arthritis refractory to NSAIDs, sulfasalazine, prednisone, and methotrexate treatment

Source: Gc.kinesis.co.uk

Etanercept – Case Report

33 year old white male

Positive for Chlamydiatrachomatis

Treated with azithromycin

3 weeks later: returns with joint pain, itching of both eyes, andkeratodermablennorrhagicum

Source: Worldstemcells.comSource: Wikipedia.org

Etanercept – Case Report Two months without improvement

◦ Ibuprofen (800 mg t.i.d)

◦ Sulfasalazine (3000 mg q.d.)

◦ Methotrexate (15 mg once a week)

◦ Prednisone (20-60 mg q.d.)

Etanercept was started

(50 mg sc. once a week)

After two months, skin and joint pain improved.

Etanercept and methotrexate were continued for

12 months with resolution and no recurrence.

Source: Sweetclipart.com

Conclusions

Etanercept is a TNF-alpha inhibitor that may be used for patients that do not respond to other treatment options

Although…

TNF-alpha has been shown to inhibit growth of bacterial organisms, but also causes an inflammatory response

In some cases, the use of TNF-alpha inhibitors may lead to worsening of symptoms

Combination Therapy

Source: Lippincott, 2006

• Treatment with

etanercept

together with

methotrexate

has been shown

to cause

remission in

patients with

reactive arthritis

Remission

Definition: ‘a period of time during a

serious illness when the patient's

health improves’

Approximately 15% of reactive

arthritis cases become chronic

and result in destructiveness of

the joints

Source: Merriam-Webster.com

Remission – Systematic Study

C. trachomatis is present and

metabolically active during the

remitting phase in synovial tissues

from patients with chronic Chlamydia-

induced reactive arthritis (Gerard,

H.C., Carter, J.D., Hudson, A.P., 2013)

4 patients in remission compared to 10

patients with active reactive arthritis…

Remission – Systematic Study

Synovial biopsies analyzed using qPCR and RT-PCR

Bacterial load of patients in remission was 20% of the load in active patients

Heat shock protein 60(hsp60), monocytechemotactic protein (MCP1), RANTES (regulated on activation, normal T cell expressed and secreted) mRNA levels were equal to or higher in remitted patients compared to active patients

Source: Aespecialists.com

Gene Expression

Source: Gerard,

H. Am J Med

Sci. Jul 2013

Gene Expression

Source: Gerard,

H. Am J Med

Sci. Jul 2013

Conclusion

Bacterial load in synovium of patients

in remission are low; proinflammatory

proteins are equal to or higher than

patients with active reactive arthritis

Organism is present and metabolically

active in synovium during remission

Genetic patterns of patients in

remission are complex

Future Research

How exactly does chlamydia replicate and how can we create therapeutic agents that target every component of these replication patterns (transcription, translation, etc.)?

How can we develop nanotechnology that introduces bactericidal agents directly into target sites in the synovium?

Source: Mynamesnotmommy.com

Future Research

Why do patients with reactive arthritis

relapse into active symptoms at low

bacterial loads?

What are the effects of

immunosuppressive drugs that

specifically target heat shock protein

60, monocyte chemotactic protein,

RANTES on patients with chronic

reactive arthritis?

Acknowledgements

Dr. FM, M.D.

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011-2000-1.

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