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Reactive Arthritis Medication

  • Author: Carlos J Lozada, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Oct 31, 2015
 

Medication Summary

The goals of pharmacotherapy for reactive arthritis (ReA) are to reduce morbidity, to prevent joint damage, and to alleviate extra-articular disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstays of therapy for joint symptoms. Other types of agents used to treat ReA or its extra-articular manifestations include corticosteroids, antibiotics, and various disease-modifying antirheumatic drugs (DMARDs).

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Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Class Summary

Several NSAIDs are available for relief of mild to moderate pain in ReA patients. They are similar with respect to effectiveness, though indomethacin may be more effective in the spondyloarthropathies. Cyclooxygenase (COX)-2–specific inhibitors can be used in patients at high risk for GI complications.

NSAIDs have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not fully known, but they may inhibit COX activity and prostaglandin synthesis. Other mechanisms, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions, may exist.

Aspirin and several NSAIDs are available for use in ReA patients and are comparably effective in treating symptoms.

Aspirin (Ascriptin, Bayer Aspirin, Bayer, Bufferin, Ecotrin Arthritis Strength)

 

Aspirin is a short-acting anti-inflammatory agent with rapid absorption in the proximal gastrointestinal (GI) tract. It is optimally effective only when stable serum levels of 150-250 µg/L are achieved after 3-5 days of treatment. Serum aspirin levels can be checked after 5-10 days of treatment. Maximal anti-inflammatory action is generally achieved within 2-4 weeks, with some further benefit occurring up to 3 months.

Ibuprofen (Motrin, Advil, NeoProfen, Addaprin)

 

Ibuprofen inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Indomethacin (Indocin)

 

Indomethacin is the NSAID of choice in ReA; however, other NSAIDs are often effective as well. It is rapidly absorbed; metabolism occurs in the liver via demethylation, deacetylation, and glucuronide conjugation. Indomethacin inhibits prostaglandin synthesis; it is also a potent COX inhibitor, and this action may decrease local production of arachidonic acid–derived chemotactic factors for eosinophils present in sebum.

Naproxen (Naprosyn, Aleve, Naprelan)

 

Naproxen is used for relief of mild-to-moderate pain and is available in both short-acting and long-acting forms. It inhibits inflammatory reactions and pain by decreasing the activity of COX, which is responsible for prostaglandin synthesis.

Diclofenac (Voltaren, Cataflam XR, Zipsor, Cambia)

 

Diclofenac inhibits prostaglandin synthesis by decreasing COX activity, which, in turn, decreases formation of prostaglandin precursors.

Ketoprofen

 

Ketoprofen is used for relief of mild to moderate pain and inflammation. Small dosages are indicated initially in small patients, elderly patients, and patients with renal or liver disease. Doses higher than 75 mg do not increase the therapeutic effects. Administer high doses with caution, and closely observe the patient's response.

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Corticosteroids

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body’s immune response to diverse stimuli. Topical corticosteroids are used for dermatologic manifestations of ReA, such as keratoderma blennorrhagicum and balanitis circinata (circinate balanitis). For ocular therapy, topical or subtenon injections of steroid have proven effective. Systemic steroids should only be used in cases of macular involvement and only for short periods.

Prednisone (Rayos)

 

Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity the activity of polymorphonuclear leukocytes (PMNs).

Prednisolone acetate 1% (Pred Forte, Pred Mild, Omnipred)

 

Prednisolone acetate is used mainly for acute iritis. The best approach is to treat aggressively early in the course of the disease, then to gradually taper and discontinue the drug on the basis of the patient's clinical response.

Hydrocortisone valerate (CortAlo, TheraCort, U-Cort, Westcort)

 

Topical corticosteroids are adrenocorticosteroid derivatives suitable for application to skin or external mucous membranes; they have mineralocorticoid and glucocorticoid effects, resulting in a nonspecific anti-inflammatory activity.

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Keratolytic Agents

Class Summary

These agents cause cornified epithelium to swell, soften, macerate, and then desquamate.

Salicylic acid topical (Calicylic, Aliclen, Keralyt, Salkera, Salvax)

 

Topical salicylic acid, by dissolving intercellular cement substance, produces desquamation of the horny layer of the skin, without affecting the structure of viable epidermis.

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Antibiotics

Class Summary

Antibiotics may be used in ReA for antibacterial effects and for treatment of possible coexistent infection. Empiric antimicrobial therapy should cover all likely pathogens in the context of the clinical setting. Whenever feasible, antibiotic selection should be guided by blood culture sensitivity.

Tetracyclines are used to treat urethritis or cervicitis caused by chlamydial organisms. Some evidence shows that tetracycline treatment in chlamydia-induced ReA may reduce the duration, and perhaps the severity, of illness. Collagenase inhibitors have been used to treat early rheumatoid arthritis.

Erythromycin (EryPed 200, E.E.S. 400, Ery-Tab, PCE)

 

Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is indicated for treatment of infections caused by susceptible strains of microorganisms (eg, Mycoplasma pneumoniae and Staphylococcus, Streptococcus, and Chlamydia spp) and for prevention of corneal and conjunctival infections.

Erythromycin ophthalmic (Romycin, Ilotycin)

 

Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is indicated for the prevention of corneal and conjunctival infections.

Ciprofloxacin (Cipro, Cipro XR)

 

Ciprofloxacin is the drug of choice for obtaining improvement in clinical parameters (except joint involvement) in postenteric ReA. It is a bactericidal antibiotic that inhibits bacterial DNA synthesis and, consequently, growth by inhibiting DNA gyrase in susceptible organisms.

Tetracycline

 

Tetracycline is used to treat gram-positive and gram-negative infections, as well as mycoplasmal, chlamydial, and rickettsial infections. It inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits.

Doxycycline (Adoxa, Doryx, Vibramycin)

 

Doxycycline is used to treat infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma organisms. It inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Minocycline (Minocin, Solodyn)

 

Minocycline is used to treat infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma organisms. It inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Azithromycin (Zithromax, Zmax)

 

Azithromycin is used to treat mild-to-moderate microbial infections.

Cefdinir

 

Cefdinir is a third-generation cephalosporin indicated for treatment of susceptible infections.

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Aminosalicylic Acid Derivatives

Class Summary

Aminosalicylic acid derivatives are used to reduce inflammation when NSAIDs do not control arthritis or when inflammatory lesions of the intestinal mucosa are present.

Sulfasalazine (Azulfidine EN-tabs, Sulfazine, Sulfazine EC)

 

Sulfasalazine is used as a second-line therapy to treat ReA that is not controlled with NSAIDs alone. It is a conjugate of the salicylate 5-aminosalicylic acid (5-ASA) and the sulfonamide sulfapyridine (linked by an azo bond). Sulfasalazine is primarily excreted in the urine unchanged. Most of the 5-ASA remains in the colon and is not absorbed. Sulfasalazine acts locally to decrease the inflammatory response in the joints and systemically inhibits prostaglandin synthesis and folate metabolism.

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Vitamins, Fat-Soluble

Class Summary

Vitamins are essential for normal synthesis of DNA and metabolism of proteins, carbohydrates, and fats.

Calcipotriene (Dovonex, Calcetrene, Sorilux)

 

Calcipotriene is a synthetic vitamin D-3 analogue that regulates skin-cell production and development. It is available as a 0.005% cream, ointment, or solution.

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Antineoplastic Agents

Class Summary

Antineoplastic agents have immunosuppressive effects and inhibit cell growth and proliferation. They are used when the disease is aggressive and unremitting.

Azathioprine (Imuran, Azasan)

 

Azathioprine may be used alone or as a steroid-sparing agent. It antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. Azathioprine may decrease proliferation of immune cells, thereby reducing autoimmune activity. It is used more commonly for ReA and psoriasis. Thiopurine methyltransferase levels should be checked before azathioprine is used.

Methotrexate (Trexall, Rheumatrex)

 

Methotrexate is an antimetabolite that is indicated for the symptomatic control of severe ReA and severe, recalcitrant, disabling psoriasis. It is also used alone or in combination with other anticancer agents in the treatment of advanced mycosis fungoides and cancer of the head, neck, or lung, particularly those of the squamous-cell and small-cell types.

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Antimalarials

Class Summary

Derivatives of 4-aminoquinoline are active against a variety of autoimmune disorders. They must be used with caution because hydroxychloroquine is known to be capable of exacerbating psoriasis. Because hydroxychloroquine is used for the joint involvement and not the skin involvement, it should probably be given only in conjunction with rheumatologic evaluation.

Hydroxychloroquine (Plaquenil)

 

It is not clear how hydroxychloroquine works. It is known to interfere with TLR signaling, inhibit chemotaxis of eosinophils neutrophils, and impair complement-dependent antigen-antibody reactions. A 200-mg quantity of hydroxychloroquine sulfate is equivalent to 155 mg of hydroxychloroquine base and 250 mg of chloroquine phosphate.

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Retinoid-like Agents

Class Summary

Retinoids decrease the cohesiveness of abnormal hyperproliferative keratinocytes and may reduce the potential for malignant degeneration. They also modulate keratinocyte differentiation.

Isotretinoin (Absorica, Claravis, Myorisan, Zenatane)

 

Oral agent used to treat serious dermatologic conditions. It is a synthetic 13-cis isomer of the naturally occurring tretinoin (trans-retinoic acid), and both agents are structurally related to vitamin A. Isotretinoin alters the pattern of keratinization, reduces bacterial flora, and has an anti-inflammatory effect.

A US Food and Drug Administration (FDA)–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin (see iPLEDGE). This registry aims to achieve further decreases in the risks of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Acitretin (Soriatane)

 

Acitretin is a retinoic acid analogue, similar to etretinate and isotretinoin. Etretinate is the main metabolite and has similar clinical effects. Acitretin's mechanism of action is unknown.

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Tumor Necrosis Factor Blockers

Class Summary

Anti–tumor necrosis factor (TNF)–α therapy may be considered in refractory cases of ReA.

Infliximab (Remicade)

 

Infliximab is a chimeric IgG1κ monoclonal antibody that binds specifically to the soluble and transmembrane forms of TNF-α and inhibits the binding of TNF-α to its receptors.

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Contributor Information and Disclosures
Author

Carlos J Lozada, MD Director of Rheumatology Fellowship Training Program, Professor of Clinical Medicine, Department of Medicine, Division of Rheumatology and Immunology, University of Miami, Leonard M Miller School of Medicine

Carlos J Lozada, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Received honoraria from Pfizer for consulting; Received grant/research funds from AbbVie for other; Received honoraria from Heel for consulting.

Coauthor(s)

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Maria F Carpintero, MD Assistant Professor of Clinical Medicine, Division Rheumatology/Immunology, University of Miami, Leonard M Miller School of Medicine

Maria F Carpintero, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Acknowledgements

Mounir Bashour, MD, CM, FRCS(C), PhD, FACS Assistant Professor of Ophthalmology, McGill University; Clinical Assistant Professor of Ophthalmology, Sherbrooke University; Medical Director, Cornea Laser and Lasik MD

Mounir Bashour, MD, CM, FRCS(C), PhD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American College of International Physicians, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, American Society of Mechanical Engineers, American Society of Ophthalmic Plastic and Reconstructive Surgery, Biomedical Engineering Society, Canadian Medical Association,Canadian Ophthalmological Society, Contact Lens Association of Ophthalmologists, International College of Surgeons US Section, Ontario Medical Association, Quebec Medical Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Igor Boyarsky, DO Emergency Room Physician, Kaiser Permanente Southern California

Igor Boyarsky, DO is a member of the following medical societies: American Academy of Anti-Aging Medicine, American Academy of Emergency Medicine, American College of Emergency Physicians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Bo Burns, DO, FACEP, FAAEM Assistant Professor, Associate Residency Director, Medical Clerkship Director, Department of Emergency Medicine, University of Oklahoma School of Community Medicine; Attending Physician, Department of Emergency Medicine

Bo Burns, DO, FACEP, FAAEM, is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Gino A Farina, MD, FACEP, FAAEM Associate Professor of Clinical Emergency Medicine, Albert Einstein College of Medicine; Program Director, Department of Emergency Medicine, Long Island Jewish Medical Center

Gino A Farina, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Lawrence K Jung, MD Chief, Division of Pediatric Rheumatology, Children's National Medical Center

Lawrence K Jung, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Rheumatology, Clinical Immunology Society, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Jeffrey Meffert, MD Assistant Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio

Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society

Disclosure: Nothing to disclose.

Barry L Myones, MD Associate Professor, Departments of Pediatrics and Immunology, Pediatric Rheumatology Section, Baylor College of Medicine; Director of Research, Pediatric Rheumatology Center, Texas Children's Hospital

Barry L Myones, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American College of Rheumatology, American Heart Association, American Society for Microbiology, Clinical Immunology Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Robert E O'Connor, MD, MPH Professor and Chair, Department of Emergency Medicine, University of Virginia Health System

Robert E O'Connor, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Physician Executives, American Heart Association, American Medical Association, Medical Society of Delaware, National Association of EMS Physicians, Society for Academic Emergency Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Lluís Puig, MD, PhD Program Director, Assistant Professor, Department of Dermatology, Hospital De La Santa Creu I Sant Pau, Universitat Autónoma De Barcelona

Lluís Puig, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, European Academy of Dermatology and Venereology, and International Society of Dermatopathology

Disclosure: Nothing to disclose.

Jorge Romaní, MD Assistant Professor, Department of Dermatology, Hospital De Palamós Faculty of Medicine, Spain

Disclosure: Nothing to disclose.

Hampton Roy Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Nima Sarani, MD Resident Physician, Department of Emergency Medicine, Oklahoma University College of Medicine

Nima Sarani, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Physicians, and Congress of Neurological Surgeons

Disclosure: Nothing to disclose.

Thomas Scoggins, MD Consulting Staff, Department of Emergency Medicine, Blount Memorial Hospital

Thomas Scoggins, MD is a member of the following medical societies: American College of Emergency Physicians and Flying Physicians Association

Disclosure: Nothing to disclose.

John D Sheppard Jr, MD, MMSc Professor of Ophthalmology, Microbiology and Molecular Biology, Clinical Director, Thomas R Lee Center for Ocular Pharmacology, Ophthalmology Residency Research Program Director, Eastern Virginia Medical School; President, Virginia Eye Consultants

John D Sheppard Jr, MD, MMSc is a member of the following medical societies: American Academy of Ophthalmology, American Society for Microbiology, American Society of Cataract and Refractive Surgery, American Uveitis Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

David D Sherry, MD Director, Clinical Rheumatology, Attending Physician, Pain Management, The Children's Hospital of Philadelphia; Professor of Pediatrics, University of Pennsylvania School of Medicine

David D Sherry, MD is a member of the following medical societies: American College of Rheumatology and American Pain Society

Disclosure: Nothing to disclose.

Dana A Stearns, MD Assistant Director of Undergraduate Education, Department of Emergency Medicine, Massachusetts General Hospital; Assistant Professor of Surgery, Harvard Medical School

Dana A Stearns, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Akaluck Thatayatikom, MD Associate Professor and Chief, Department of Pediatrics, Division of Pediatric Allergy, Immunology, and Rheumatology, University of Kentucky College of Medicine

Akaluck Thatayatikom, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Rheumatology, Childhood Arthritis and Rheumatology Research Alliance, and Clinical Immunology Society

Disclosure: Nothing to disclose.

Robin Travers, MD Assistant Professor of Medicine (Dermatology), Dartmouth University School of Medicine; Staff Dermatologist, New England Baptist Hospital; Private Practice, SkinCare Physicians

Robin Travers, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Informatics Association, Massachusetts Medical Society, Medical Dermatology Society, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

R Christopher Walton, MD Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, University of Tennessee College of Medicine

R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Research in Vision and Ophthalmology, and Retina Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Balanitis circinata (circinate balanitis) in patient with reactive arthritis.
Plaques on soles of patient with reactive arthritis.
Painful erosions on fingers in patient with reactive arthritis.
Plaques and erosions of tongue in patient with reactive arthritis.
Radiograph of feet of 27-year-old man shows erosions in all left metatarsophalangeal (MTP) joints with subluxation and valgus deformity of most toes. Smaller erosions are also visible in fourth and fifth MTP joints of right foot.
Lateral radiograph of foot reveals calcaneal spur and enthesitis.
Radiograph of both hands shows small erosive changes in both first metacarpal heads associated with minimal subluxation. Bone density is normal.
Radiography of pelvis reveals bilateral asymmetric sacroiliitis.
Radiograph in 40-year-old man shows nonmarginal syndesmophytes predominantly in lower thoracic and upper lumbar spine.
Swelling of right knee with effusion caused by arthritis. Image courtesy of Gun Phongsamart, MD.
Remarkable tenderness of left sacroiliac joint caused by sacroiliitis. Image courtesy of Gun Phongsamart, MD.
Balanitis circinata (circinate balanitis). Image courtesy of Gun Phongsamart, MD.
Achilles tendinitis and swelling of retrocalcaneal bursa.
 
 
 
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