TRIPASS XR تري باس

 

The annual incidence reported varies between 9 and 27 for reactive

arthritis/100,000/year. Patients with an acute Chlamydia infection develop reactive

arthritis. Reactive arthritis most frequently occurs in patients between 20 and 40

years of age, but it can occur at any age. In general, it occurs more frequently in men

than in women following genitourinary infection, which is most commonly a sexually

transmitted disease. Following bowel infections, the prevalence is equal between

men and women.

37

Reactive arthritis is considered a sterile inflammatory response to a remote

infection. Reactive arthritis usually occurs after an infection in a genetically

susceptible person, which has been identified as a likely risk factor. Genetics may

play a role in pathogenesis of spondyloarthropathies; 30% to 50% of patients are

surface antigen HLA-B27 positive, which presents antigenic peptides to T cells.

These patients are susceptible to a more severe and prolonged disease.

37 The HLAB27 gene has a higher prevalence in the Caucasian population.

39

Table 46-5

Examples of Bacterial Pathogens Associated with the Development of Reactive

Arthritis

Gastrointestinal

Salmonella enteritidis and typhimurium

Shigella flexneri

Yersinia enterocolitica and pseudotuberculosis

Campylobacter jejuni

Escherichia coli

Clostridium difficile

Genitourinary

Chlamydia trachomatis

Neisseria gonorrhoeae

Respiratory

Chlamydia pneumoniae

Group A β-hemolytic streptococcus

Source: Hill Gaston JS. Reactive arthritis and undifferentiated spondyloarthritis. In: Firestein G et al, eds. Kelley’s

Textbook of Rheumatology. 9th ed. Philadelphia, PA: Saunders Elsevier; 2013:1221; Reactive arthritis. In

DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – [cited 2010 March 23].

http://www.dynamed.com. Registration and login required. Accessed July 8, 2015; Hannu T. Reactive arthritis.

Best Pract Res Clin Rheumatol. 2011;25:347; Selmi C, Gershwin ME. Diagnosis and classification of reactive

arthritis. Autoimmun Rev. 2014;13:546.

Onset of symptoms typically occurs 1 to 3 weeks later and may present in an

insidious or acute manner. Patients usually present with a chief complaint of

mucocutaneous lesions, joint stiffness, myalgia, and low back pain that is worse with

rest. Table 46-6 describes the clinical manifestations of reactive arthritis. It may

present as arthritic in nature or as dysfunctions of the ocular, skin, genitourinary, or

cardiac systems. Urethritis, mild dysuria, and a mucopurulent urethra are the most

common symptoms that occur in men. Women may have dysuria, vaginal discharge,

and purulent cervicitis or vaginitis. Arthritic complaints are usually asymmetrical,

involving the lower extremities, and are associated with the appearance of a

“sausage finger” digit.

36

CASE 46-3

QUESTION 1: T.K. is a 37-year-old man who presented to the outpatient primary-care clinic 2 weeks after

the onset of a low-grade fever associated with pain and stiffness in his left knee and right ankle, pain on

urination, and red, irritated eyes. He reports no recent injuries. The patient reports that the last time he engaged

in unprotected sex was 3 weeks ago. T.K. denies experiencing chest pain, skin rash, photosensitivity, genital

lesions, or urethral discharge and hematuria. Swelling, erythema, and tenderness of the left knee joint, as well as

signs of conjunctivitis, were the only findings noted on physical examination. A urine Chlamydia rapid test with

first void was positive.

He reports no current medical conditions and a family history of psoriatic arthritis.

Based on the history of symptoms present in this case, what supports a diagnosis of reactive arthritis?

T.K. presents with multiple symptoms following a confirmed infection with

Chlamydia trachomatis. He is presenting with an inflamed joint in the lower

extremity and also conjunctivitis. Urethritis can be a symptom associated with

reactive arthritis but in this case overlaps as a potential symptom of an active

Chlamydia infection. A family history of psoriatic arthritis, which is also under the

classification as a spondyloarthropathy, may indicate a risk factor for severe or

chronicity if T.K. has the HLA-B27 gene. Laboratory testing for the gene is not

required for diagnosis.

36,37

Table 46-6

Clinical Signs of Reactive Arthritis

Musculoskeletal System

Arthritis affecting 1–4 joints

Entheses

Extra-articular disease

Skin Manifestations

Keratoderma blennorrhagica on soles and/or palms

Circinate balanitis on penile gland

Ocular Manifestations

Mucosal ulcers

Conjunctivitis

Uveitis

Source: Hill Gaston JS. Reactive arthritis and undifferentiated spondyloarthritis. In: Firestein G et al, eds. Kelley’s

Textbook of Rheumatology. 9th ed. Philadelphia, PA: Saunders Elsevier; 2013:1221.

p. 926

p. 927

CASE 46-3, QUESTION 2: What is an appropriate initial treatment strategy for T.K.?

Empiric antibiotic therapy does not reduce the risk of recurrence of reactive, and

antibiotics are therefore not routinely recommended for uncomplicated cases. As is

the case with T.K., an active documented infection such as Chlamydia in the urine or

bacteria in the stool in gastrointestinal infections should receive treatment. It is

possible that by the time arthritis presents stool cultures would be negative following

a gastrointestinal foodborne illness. Those with documented Chlamydia trachomatis

infection and their partners should be offered antibiotics (azithromycin 1 g orally as a

single dose or doxycycline 100 mg twice/day for 7 days).

37,38 Further information on

appropriate antibiotic therapy for the infections that can cause reactive arthritis can

be found in the chapters in Section 14: Infectious Disease. Although some studies

have reported success of prolonged use of combination antibiotics specifically in

reactive arthritis following Chylmadia,

37,40 a meta-analysis evaluating the efficacy of

antibiotics in the routine treatment of reactive arthritis concluded that they did not

induce remission, but this issue remains uncertain due to heterogeneity of the

studies.

41 Antibiotic use was associated with a 97% increase in gastrointestinal side

effects.

41

Oral nonsteroidal anti-inflammatory drugs may be useful for pain control and

inflammation, but there is no evidence that they affect arthritis itself or shorten the

clinical course.

37

CASE 46-3, QUESTION 3: Three weeks later, T.K. reports that he has had resolution of the low-grade

fever and any pain on urination but that he is not receiving adequate pain relief in his knee. He complains that it

is limiting his activities. What additional therapies can be considered?

Because T.K. is still experiencing pain in his left knee, an intra-articular

corticosteroid injection, or oral corticosteroids if more joints are affected, may be

considered. Intra-articular corticosteroid injections do not have as dramatic or as

sustained a response as in those with rheumatoid arthritis. However, they may be

helpful for the treatment of pain and swelling. For those who suffer from a

persistence of reactive arthritis, a disease-modifying antirheumatic drug such as

sulfasalazine is well tolerated and possibly effective at a dose of 1 g 2 or 3 times

daily. Consideration may be given to start DMARD therapy earlier in the course of

the disease if a patient is having a recurrence of reactive arthritis or is HLA-B27

positive.

36 Aggressive and unremitting reactive arthritis may be treated with

immunosuppressants, if it is confirmed the initial infection is cleared. In severe

cases, where patients fail to achieve adequate relief with prior therapies, antitumor

necrosis factor (TNF)-α treatment may be considered. Limited evidence is available

and is discussed in the literature primarily through case reports. Physical therapy

modalities may be an integral part of management to improve mobility and strength

and to prevent stiffness and deformities if needed.

36–38

Polymyositis and Dermatomyositis

Polymyositis (PM) and dermatomyositis (DM) are idiopathic autoimmune and

inflammatory disorders of unknown etiology involving a number of voluntary skeletal

muscles simultaneously. PM and DM are characterized by the presence of

inflammatory myopathies. In addition, DM involves specific skin manifestations,

whereas PM does not.

42,43 Dermatomyositis is also associated with an increased risk

of malignancies. Fifteen percent of patients over 40 years of age have a preexisting

malignancy or will develop one in the future.

44 Therapy is aimed at reducing the risk

of respiratory failure, renal failure, and cardiomyopathy as potential complications of

either disorder. A proportion of patients (approximately 11%– 40% of those with

DM) will meet the diagnostic criteria for other CTDs. This overlap syndrome is

thought to occur more frequently in men than in women (9:1 ratio). Patients with

myositis are likely, reported in 11% to 40%, to have another connective tissue

disease (e.g., scleroderma, SLE, rheumatoid arthritis, and sarcoidosis).

45

PM typically presents between the ages of 50 and 60 years and is rarely seen in

children. DM exhibits a bimodal distribution and affects adults between the ages of

45 and 65 years, as well as a peak in children aged 5 to 15. African-Americans are at

an increased risk for these disorders, and both women and men (2:1) are affected.

45

For dermatomyositis, the prevalence in the United States is 5.8 cases/100,000

individuals. In the United Kingdom, the prevalence among children was reported as

3.2/million. Polymyositis is reported in the United States at a prevalence of

9.7/100,000, but it should be noted that polymyositis is a diagnosis that is more

difficult to make due to overlap of symptoms with other myopathies.

46 The

prevalence is thought to lie between 50 and 100 cases/million for idiopathic

inflammatory myopathies.

42

There is no clear cause of either disorder, and both are thought to involve immunemediated processes triggered by environmental factors (autoimmune or viral) in

genetically susceptible individuals. DM is thought to be a complement-mediated

microangiopathy in which inflammatory infiltrates arise owing to ischemic

phenomena. In patients with PM, muscle fibers may be damaged by cytotoxic CD8 T

lymphocytes. Infectious agents implicated as causative factors include

coxsackievirus, influenza virus, retroviruses, cytomegalovirus, and Epstein–Barr

virus. Various autoantibodies are found in up to 60% of patients. Expression of a

genetic-specific HLA subtype (HLA DRB1-03 in whites and HLA DRB1-14 in

Koreans) places individuals from certain ethnic groups at an increased risk.

Exposure to UV radiation also increases the risk of developing DM.

45

Symptom onset for both PM and DM is insidious, and patients initially complain of

muscle weakness of the trunk, shoulders, hip girdles, upper arms, thighs, neck, and

pharynx. These patients usually report increasing difficulties in everyday tasks

requiring the use of proximal muscles such as getting up from a chair, climbing stairs,

stepping onto a curb, lifting objects, and combing hair. Frequent falls, fatigue,

malaise, weight loss, shortness of breath, and low-grade fever are also often present.

Classification of PM and DM can be accomplished by assessing the presence or

absence of certain characteristics unique to the condition. Polymyositis rarely affects

children as compared to dermatomyositis that occurs more frequently. Specifically,

they are largely separated by the involvement of cutaneous changes and calcinosis in

dermatomyositis. Specific manifestations seen in DM are described in Table 46-7.

47

At present, no diagnostic criteria for PM and DM have been clearly defined and

validated. After other conditions (e.g., human immunodeficiency virus (HIV)

infection, lichen planus, SLE, psoriasis, or drug-induced causes) have been

considered and ruled out, diagnosis may be confirmed by generally accepted criteria

including the presence of proximal muscle weakness, elevated serum concentrations

of skeletal muscle enzymes (e.g., creatine kinase, lactate dehydrogenase), myopathic

changes on electromyography, evidence of inflammation on muscle biopsy, and skin

rash (for DM only).

45,47,48

CASE 46-4

QUESTION 1: J.A. is a 45-year-old white woman with a history of PM. She was initially diagnosed 1 year

ago and was treated with high-dose oral prednisone for 3 months, at which time an attempt to taper the

corticosteroid to the lowest effective dose

p. 927

p. 928

was initiated. Since that time, J.A. has not been able to completely stop corticosteroid therapy without the

recurrence of muscle weakness, which affects her ability to perform activities of daily living. In the past 3

months, her symptoms have progressed to the point where she was titrated back to his initial high-dose

prednisone regimen in an attempt to gain adequate relief. At this point, J.A. and her primary-care physician are

considering alternative options for symptom control. What is a reasonable pharmacotherapeutic option to

recommend that may provide J.A. with symptom relief?

The initial and long-term goals of therapy are to improve muscle weakness,

thereby improving the activities of daily living. The clinical course of both PM and

DM varies in severity from mild to more severe progressive disease. Those with

mild forms of the disease usually have a rapid response to therapy, whereas those

with more severe or slowly progressive forms of the disease are more likely to not

respond to treatment; this is a marker for a poor prognosis. As demonstrated in J.A.’s

case, initial therapy with high-dose corticosteroids (e.g., 1 mg/kg) is used, followed

by slow taper depending on response to therapy. The approach may include a switch

to alternate day dosing during the taper or a 10% reduction in dose every 2

weeks.

45–49

In severe cases, it may be preferred to begin with intravenous

corticosteroid therapy with methylprednisolone for 3 to 5 days at a dose of 1,000 mg.

Patients who respond early to high-dose corticosteroids typically respond better to

corticosteroid-sparing agents (e.g., methotrexate, azathioprine) in the future. J.A.’s

failure to respond to corticosteroids should prompt further investigation for other

possible pathologic processes including muscular dystrophy, hypothyroidism, or

malignancy-associated myopathy. Should those investigations yield no conclusive

results, J.A. may be offered methotrexate, azathioprine, mycophenolate mofetil, or

cyclosporine as recommended immunosuppressants and steroid-sparing agents if the

disease is not controlled with corticosteroids alone, is rapidly progressive, or

presents with extramuscular involvement. If the complication of interstitial lung

disease is present, cyclophosphamide or tacrolimus may be considered. If a patient

does not have a sufficient response to corticosteroids, then intravenous immune

globulin can be given over 2 to 5 days.

42,45,49 Ongoing trials will evaluate the

potential use of other immune-modulating therapies.

Table 46-7

1.

2.

1.

2.

3.

1.

2.

Cutaneous Manifestations of Dermatomyositis

Pathognomonic Skin Lesions of DM

Gottron papules: papules having a violaceous hue overlying the dorsal lateral aspect of interphalangeal and/or

metacarpophalangeal joints. When fully formed, these papules become slightly depressed at the center

which can assume a white, anthropic appearance. Associated telangiectasia can be present.

Gottron signs:symmetric macular violaceous erythema with or without edema overlying the dorsal aspect of

the interphalangeal/metacarpophalangeal joints, olecranon processes, patellae, and medial malleoli.

Highly Characteristic Skin Lesions of DM

Periorbital violaceous (heliotrope) erythema with or without associated edema of the eyelids and periorbital

tissue.

Grossly visible periungual telangiectasia with or without dystrophic cuticles.

Symmetric macular violaceous erythema overlying the dorsal aspect of the hands and fingers (where it can

track the extensor tendon sheaths), extensor aspects of the arms and forearms, deltoids, posterior shoulders

and neck (the shawlsign), V-area of anterior neck and upper chest, central aspect of the face and

forehead.

Compatible Skin Lesions of DM

Poikiloderma vasculare atrophicans (poikilodermatomyositis) circumscribed violaceous erythema with

associated telangiectasia, hypopigmentation, hyperpigmentation, and superficial atrophy most commonly

found over the posterior shoulders, back, buttocks, and V-area of the anterior neck and chest.

Calcinosis cuts.

Reprinted with permission from Iaccarino L et al. The clinical features, diagnosis and classification of

dermatomyositis. J Autoimmun. 2014;48:122–127.

CASE 46-4, QUESTION 2: What preventive health measures may be offered to J.A. to augment her

pharmacotherapeutic treatment regimen?

Supportive therapies such as bed rest, physiotherapy, warm baths, and moist heat

applications to the affected areas can improve muscle stiffness. If oral lesions are

present, irrigation of these lesions with warm saline solution is helpful. Preventive

health measures for those experiencing either disorder include application of

sunscreen, osteoporosis prevention, minimizing aspiration risk in patients with

esophageal dysmotility, and physical therapy or customized exercise in patients with

muscle weakness.

45 Although there has been previous concern to not further damage

muscle, appropriate exercises including passive range of motion exercises and

aerobic and resistance exercises have shown benefit.

44 Female patients placed on

teratogenic immunosuppressants should discuss contraception, when appropriate.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

Key References

Barber C et al. Antibiotics for treatment of reactive arthritis: a systemic review and metaanalysis. J Rheumatol.

2013;40:916. (40)

Carsten P, Schmidt J. Diagnosis, pathogenesis and treat of myositis: recent advances. Clin Exp Immunol.

2014:175:425. (45)

Dasgupta B et al. BSR and BHPR guidelines for the management of polymyalgia rheumatica. Rheumatology

(Oxford). 2010;49:186. (29)

Findlay A et al. An overview of polymyositis and dermatomyositis. Muscle Nerve. 2015;51:638. (43)

Hill Gaston JS. Reactive arthritis and undifferentiated spondyloarthritis. In: Firestein G et al, eds. Kelley’s Textbook

of Rheumatology. 9th ed. Philadelphia, PA: Saunders Elsevier; 2013:1221. (36)

Hinchcliff M, Varga J. Systemic sclerosis/scleroderma: a treatable multisystem disease. Am Fam Physician.

2008;78:961. (3)

Kowal-Bielecka O et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the

EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis. 2009;68(5):620. (12)

Key Websites

Arthritis Foundation. Reactive Arthritis. http://www.arthritis.org/about-arthritis/types/reactivearthritis/symptoms.php. Accessed June 25, 2015.

Inflammatory myopathies. American College of Rheumatology. http://www.rheumatology.org/I-Am-A/PatientCaregiver/Diseases-Conditions/Inflammatory-Myopathies. Accessed August 16, 2015.

The Myositis Foundation. http://www.myositis.org/. Accessed August 16, 2015.

COMPLETE REFERENCES CHAPTER 46 CONNECTIVE

TISSUE DISORDERS

Alarcon GS. Unclassified or undifferentiated connective tissue disease. In: Koopman WJ et al, eds. Clinical Primer

of Rheumatology. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:213.

Mosca M et al. The diagnosis and classification of undifferentiated connective tissue diseases. J Autoimmun.

2014;48:50–52.

Hinchcliff M, Varga J. Systemic sclerosis/scleroderma: a treatable multisystem disease. Am Fam Physician.

2008;78:961.

Mayes MD et al. Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US

population. Arthritis Rheum. 2003;48:2246.

Medsger TA Jr. Systemic sclerosis and Raynaud syndrome. In: Koopman WJ et al, eds. Clinical Primer of

Rheumatology. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:171.

Laing TJ et al. Racial differences in scleroderma among women in Michigan. Arthritis Rheum. 1997;40:734.

Systemic sclerosis. In DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995—[cited August 17,

2015]. http://www.dynamed.com. Registration and login required. Accessed August 17, 2015.

Chaudhary P et al. Cigarette smoking is not a risk factor for systemic sclerosis. Arthritis Rheum. 2011;63:3089.

Tan EM et al. Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum. 1997;40:1601.

Van den Hoogen et al. 2013 classification criteria for systemic sclerosis: an American college of

rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013;72:1747.

Zulian F et al. The pediatric Rheumatology European Society/american College of Rheumatology/European

League against Rheumatism provisional classification criteria for juvenile systemic sclerosis. Arthritis Rheum.

2007;57:203.

Kowal-Bielecka O et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the

EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis. 2009;68:620.

Usatine RP, Diaz L. Scleroderma (progressive systemic sclerosis). Barry HC, Smith M, Lind-bloom E, eds.

http://www.essentialevidenceplus.com. Accessed August18, 2015.

Thompson AE, Pope JE. Calcium channel blockers for primary Raynaud’s phenomenon: a meta-analysis.

Rheumatology (Oxford). 2005;44:145.

Pope J et al. Prazosin for Raynaud’s phenomenon in progressive systemic sclerosis. Cochrane Database Syst

Rev. 2000;(2):CD000956.

Dziadzio M et al. Losartan therapy for Raynaud’s phenomenon and scleroderma: clinical and biochemical findings

in a fifteen-week, randomized, parallel-group, controlled trial. Arthritis Rheum. 1999;42:2646.

Schiopu E et al. Randomized placeb-controlled crossover trial of tadalafil in Raynaud’s phenomenon secondary to

systemic sclerosis. J Rheumatol. 2009;36:2264.

Shenoy PD et al. Efficacy of tadalafil in secondary Raynaud’s phenomenon resistant to vasodilatory therapy: a

double-blind randomized cross-over trial. Rheumatology (Oxford). 2010;49:2420.

Korn JH et al. Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin

receptor antagonist. Arthritis Rheum. 2004;50:3985.

Abou-Raya A et al. Statins: potentially useful in therapy of systemic sclerosis-related Raynaud’s phenomenon and

digital ulcers. J Rheumatol. 2008;35:1801.

Denton CP et al. Renal complications and scleroderma renal crisis. Rheumatology (Oxford). 2009;48(Suppl

3):iii32.

Tashkin DP et al. Cyclophosphamide versus placebo in scleroderma lung disease. N EnglJ Med. 2006;354:2655.

Nannini C et al. Effects of cyclophosphamide on pulmonary function in patients with scleroderma and interstitial

lung disease: a systematic review and meta-analysis of randomized controlled trials and observational

prospective cohort studies [published correction appears in Arthritis Res Ther. 2009;11:408]. Arthritis Res Ther.

2008;10:R124.

Caylor TL et al. Recognition and management of polymyalgia rheumatica and giant cell arteritis. Am Fam

Physician. 2013;88:676.

Salvarani C et al. Polymyalgia rheumatica and giant-cell arteritis. N EnglJ Med. 2002;347:261.

Unwin B et al. Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006;74:1547.

Lawrence RC et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States.

Part II. Arthritis Rheum. 2008;58:26.

Salvarani C et al. The incidence of giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations in a

cyclic pattern. Ann Intern Med. 1995;123:192.

Dasgupta B et al. BSR and BHPR guidelines for the management of polymyalgia rheumatica. Rheumatology

(Oxford). 2010;49:186.

Smetana GW, Shmerling RH. Does this patient have temporal arteritis? JAMA. 2002;287:92.

Hunder GG et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis.

Arthritis Rheum. 1990;33:1122.

Dasgupta B et al. Management guidelines and outcome measures in polymyalgia rheumatica (PMR). Clin Exp

Rheumatol. 2007;25(6 Suppl 47):130.

Giant cell arteritis (including temporal arteritis). In DynaMed [Internet]. Ipswich (MA): EBSCO Information

Services. 1995—[cited August 17, 2015]. http://www.dynamed.com. Registration and login required.

Accessed August 17, 2015.

Jover JA et al. Combined treatment of giant-cell arteritis with methotrexate and prednisone. a randomized,

double-blind, placebo-controlled trial. Ann Intern Med. 2001;134:106.

Mackie SL et al. Should I send my patient with previous giant cell arteritis for imaging of the thoracic aorta? A

systematic literature review and meta-analysis. Ann Rheum Dis. 2014;73:143.

Hill Gaston J.S. Reactive arthritis and undifferentiated spondyloarthritis. In: Firestein G et al, eds. Kelley’s

Textbook of Rheumatology. 9th ed. Philadelphia, PA: Saunders Elsevier; 2013:1221.

Reactive arthritis. In DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995—[cited March 23,

2010]. http://www.dynamed.com. Registration and login required. Accessed July 8, 2015.

Hannu T. Reactive arthritis. Best Pract Res Clin Rheumatol. 2011;25:347.

Selmi C, Gershwin ME. Diagnosis and classification of reactive arthritis. Autoimmun Rev. 2014;13:546.

Zeidler H, Hudson A. New insights into Chlamydia and arthritis. Promise of a cure? Ann Rheum Dis.

2014;73:637.

Barber C et al. Antibiotics for treatment of reactive arthritis: a systemic review and meta-analysis. J Rheumatol.

2013;40:916.

Idiopathic inflammatory myopathy. In DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995—

[cited March 23, 2010]. http://www.dynamed.com. Registration and login required. Accessed July 8, 2015.

Dermatomyositis. In DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995—[cited March 23,

2010]. http://www.dynamed.com. Registration and login required. Accessed July 8, 2015.

Findlay A et al. An overview of polymyositis and dermatomyositis. Muscle Nerve. 2015;51:638.

Nagaraju K, Lundberg I. Inflammatory disease of muscle and other myopathies. In: Firestein G et al, eds.

Kelley’s Textbook of Rheumatology. 9th ed. Philadelphia, PA: Saunders Elsevier; 2013:1404.

Carsten P, Schmidt J. Diagnosis, pathogenesis and treat of mysositis: recent advances. Clin Exp Immunol.

2014:175:425.

Iaccarino L et al. The clinical features, diagnosis and classification of dermatomyositis. J Autoimmun.

2014;48:122.

Milisenda JC et al. The diagnosis and classification of Polymyositis. J Autoimmun. 2014;48:118.

Dalakas M. Inflammatory muscle diseases. N EnglJ Med. 2015;372:1734.

p. 928

Contraceptive choice is based on several factors that include

formulation, hormone content, effectiveness, side effect profile, cost,

accessibility, past medical history, medication use, privacy of use,

prevention of sexually transmitted infections (STIs), and return to

fertility time.

Case 47-1 (Question 1)

Combined hormonal contraceptive (CHC) agents are a combination of

estrogen and progestin. They are available in a variety of formulations

that include a combination of estrogen and progestin (oral tablet, vaginal

ring, and transdermal patch). CHCs may be classified by estrogen

content into high dose (50 mcg of ethinyl estradiol), low dose (30–35

mcg of ethinyl estradiol), and very low dose (10–25 mcg of ethinyl

estradiol), and can vary in cycle length (e.g., 21, 24, or 84 days of active

hormone). Combined oral contraceptives (COCs) can be further

classified by hormone content into monophasic, biphasic, triphasic, and

quadriphasic.

Case 47-1 (Questions 3–5,

7),

Table 47-3

CHCs have benefits aside from pregnancy prevention that include

treatment of acne, hirsutism, premenstrualsyndrome (PMS) and

premenstrual dysphoric disorder (PMDD), and endometrial cancer;

menstrual cycle regulation; and prevention of ovarian cancer and

functional ovarian cysts.

Case 47-2 (Questions 1–3)

Breakthrough bleeding, nausea, acne, and weight gain are among the

most commonly reported side effects in women taking hormonal

contraceptives. Risks and side effects may be linked to estrogenic,

progestogenic, or androgenic properties of hormonal contraceptives.

Case 47-2 (Questions 4–8),

Case 47-3 (Question 1),

Table 47-4

There are risks associated with CHCs and contraindications for use in

some women. Estrogen-containing contraceptives should be avoided in

women who are 35 years or older and smoke more than 15

cigarettes/day, and should have uncontrolled hypertension, history of

gallbladder disease, stroke, migraines with aura, cardiovascular disease,

and history of thromboembolic events.

Case 47-1 (Question 2)

Progestin-only contraceptives are alternative agents for women with

contraindications to CHCs. Progestin-only contraceptives vary in

Case 47-3 (Questions 2–6)

formulations that include oral tablet, depot and subcutaneous injection,

and subdermal implant. Common side effects include weight gain, acne,

mood changes, and irregular menses.

Effectiveness of hormonal contraceptives is in part based on proper use

and counseling. Patients need to understand how to use the

contraceptive, what to do for mishaps (e.g., missed dose, vaginal ring

falls out, transdermal patch falls off), and when to use a backup method.

Directions for missed doses of progestin-only contraceptives vary from

those for COCs.

Case 47-1 (Question 6, 7),

Case 47-3 (Questions 2–6)

p. 929

p. 930

Concomitant use of certain drugs may increase or decrease the levels of

hormonal contraceptive agents. In particular, antibiotics and hepatic

inducers may decrease the effectiveness of CHCs. Progestin-only

contraceptives or nonhormonal contraceptives including backup methods

may be alternatives in these cases.

Case 47-1 (Question 8),

Table 47-5

Intrauterine devices (IUDs) or intrauterine systems (IUSs) are available

in two formulations (copper IUD and levonorgestrel IUS) and are best

for long-term pregnancy prevention. To avoid the risk of pelvic

inflammatory disease, the products should be used in women involved in

a monogamous relationship.

Case 47-3 (Question 7)

Some nonhormonal contraceptives include diaphragms, condoms, and

spermicides. Male and female condoms are the only contraceptive

products that also provide protection against STIs.

Case 47-4 (Questions 1, 2)

Timing is a key for emergency contraception (EC) to be effective. It is

best taken as soon as possible after unprotected sexual intercourse but

may be effective up to 120 hours after coitus. Emergency contraception

can be in the form of high-dose progestin pills, high-dose estrogen and

progestin pills (known as Yuzpe method), selective progesterone

receptor modulator (SPRM), or copper IUD.

Case 47-4 (Question 3)

Medical abortion generally consists of mifepristone or methotrexate (to

stop development of the pregnancy), or both, in combination with

misoprostol (to induce uterine contractions and expel the pregnancy).

Case 47-4 (Question 4)

EPIDEMIOLOGY

The world population is greater than 7.3 billion people.

1

In the United States, there

are approximately 325 million people, and there is one birth every 8 seconds and 1

death every 12 seconds. This results in an increase in one person every 13 seconds.

1

Contraception is currently an issue worldwide. Preventing unintended pregnancy is

an important goal of contraceptive use, particularly in countries where population

control is a goal. Economic implications play a role as well. Data from 2008 to 2011

show an estimated 45% of pregnancies in the United States were unintended, and of

these, 42% resulted in abortions.

2 Proper use and understanding of contraceptives is

important for preventing unintended pregnancies.

HORMONAL CONTRACEPTION BACKGROUND

AND PHARMACOLOGY

Hormonal contraceptives include combinations of estrogens and progestins known as

combination hormonal contraceptives (CHCs) or progestin-only contraceptives.

Estrogens prevent the development of the dominant follicle by suppressing folliclestimulating hormone (FSH) secretion and stabilize the endometrial lining to minimize

breakthrough bleeding (see Chapter 50, Disorders Related to the Menstrual Cycle,

for more information about the menstrual cycle).

3 Progestins prevent ovulation by

suppressing luteinizing hormone (LH) secretion. They may work in combination with

estrogen in CHCs such as combination oral contraceptives (COCs), the contraceptive

patch, and the contraceptive ring, or alone in formulations such as the progestin-only

pill (POP), depot intramuscular or subcutaneous injection, subdermal implant, and as

part of intrauterine systems. Progestin-only contraceptives hamper the transport of

sperm through the cervical canal by thickening cervical mucus and causing alterations

in the endometrial lining (so that it is not favorable for implantation) and in the

fallopian tubes (affecting ovum transport).

COMBINATION HORMONAL CONTRACEPTIVES

Patient Evaluation

CASE 47-1

QUESTION 1: S.F., a healthy 33-year-old woman, presents to the clinic stating she is getting married soon

and would like birth control pills as a method of contraception. She does not have children but would like to start

a family in a year or two. Her past medical history is noncontributory other than occasional headaches for

which she takes ibuprofen 200 mg by mouth (PO) as needed.

Vitalsigns: weight, 128 lb; height, 5 feet 4 inches

Blood pressure, 122/72 mm Hg

Heart rate, 85 beats/minute

Temperature, 98.6°F

Social history:smokes one pack/day, denies alcohol

Family history:sister gestational diabetes, mother hypertension, father unknown

Which factors are important in the selection of a contraceptive agent for S.F.?

There are several factors that affect selection of a contraceptive. Among them is

effectiveness in preventing pregnancy. It is important to determine the importance of

pregnancy prevention for S.F. and choose a method based on this information. For

example, patients taking teratogenic medications or those with underlying medical

conditions in which pregnancy may not be desired will require a highly effective

birth control method or multiple methods. Others may not desire a pregnancy, but for

a variety of reasons an unintended pregnancy may be more acceptable.

The effectiveness of contraceptive methods depends on the mechanism of action,

availability (e.g., prescription required), patients’ concurrent medications, past

medical history, and acceptability (e.g., side effects, ease of use, adherence, cost, and

religious and social beliefs). Any or all of these factors can account for the

discrepancy between the lowest failure rate observed for 1 year

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in clinical trials (perfect-use failure rate) and the actual failure rate in users

(typical-use failure rate) and should be taken into account when selecting a method of

contraception (Table 47-1).

3 Return to fertility time is also an important factor to

consider. Some contraceptive methods allow a woman to conceive shortly after

discontinuation, whereas others may delay fertility longer. S.F. indicated she would

like to have children in the near future. Given her age of 33 (fertility decreases more

rapidly after age 30) and desire for future pregnancy, it would be best to select a

product with a faster return to fertility.

4 However, other factors to consider when

selecting a contraceptive agent for S.F. include contraindications and risks for her

that may indicate one method over another. A combined hormonal contraceptive

(CHC) is used commonly in women and may be appropriate for S.F. once all factors

are considered.

Contraindications to Combined Hormonal

Contraceptive Use

CASE 47-1, QUESTION 2: Are CHCs an appropriate form of contraception for S.F.? What

contraindications to CHC therapy must be considered?

To determine whether any contraindications or precautions exist, the clinician

should first obtain baseline health information from S.F. such as past medical history,

social history, and family history (Fig. 47-1).

5 The World Health Organization has

developed medical eligibility criteria to identify appropriate contraception for

patients with specific conditions. In 2010, the Centers for Disease Control and

Prevention adopted those guidelines for recommendations in the United States and

updated them in 2016 (See

http://who.int/reproductivehealth/publications/family_planning/MEC-5/en/.

Accessed June 11, 2017) html for the WHO Medical Eligibility Criteria and CDC

link).

6,7 Most data regarding contraindications are based on COCs, but the

conclusions are applied to all CHCs (e.g., vaginal ring and transdermal patch).

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Table 47-1

Percentage of Women Experiencing an Unintended Pregnancy During the First

Year of Typical Use and the First Year of Perfect Use of Contraception and the

Percentage Continuing Use at the End of the First Year: United States

Method

% of Women Experiencing an

Unintended Pregnancy Within

the First Year of Use

% of Women

Continuing

Use at 1 Year

c Relative Cost

k Typical Use

a Perfect Use

b

Chance

d 85 85 —

Fertility awareness-based methods 24 — 47 None

Standard Days method

e 5

TwoDay method

e — 4 —

Ovulation method

e — 3 —

Symptothermal

e — 0.4 —

Withdrawal 22 4 46

Spermicides

f 28 18 42 $–$$

Barrier methods

Sponge $$

Parous women 24 20 42

Nulliparous women 12 9 57

Diaphragm

g 12 6 57 $$$

Condom

h $

Female (Reality) 21 5 41

Male 18 2 43

Hormonal contraceptives

Injectable MPA 6 0.2 56 $$$

l

Pill

Progestin only 9 0.3 67 $$-$$$

Combined 9 0.3 67 $$-$$$

Transdermal patch 9 0.3 67 $$-$$$

Vaginal ring 9 0.3 67 $$-$$$

IUD/IUS — — — $$$$

l

Copper 0.8 0.6 78

Levonorgestrel 0.2 0.2 80

Female sterilization 0.5 0.5 100 $$$$m

Male sterilization 0.15 0.10 100 $$$$m

Emergency contraceptive pills $$$

Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%.

i

Lactational amenorrhea method None

LAM is a highly effective, temporary method of contraception.

j

aAmong typical couples who initiate use of a method (not necessarily for the first time), the percentage who

experience an accidental pregnancy during the first year if they do not stop use for any other reason. Estimates of

the probability of pregnancy during the first year of typical use for spermicides, withdrawal, fertility awarenessbased methods, the diaphragm, the male condom, the oral contraceptive pill, and Depo-Provera are taken from the

1995 National Survey of Family Growth corrected for underreporting of abortion; see the source for the derivation

of estimates for the other methods.

bAmong couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both

consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do

not stop use for any other reason. See the table source for the derivation of estimates for the other methods.

cAmong couples attempting to avoid pregnancy, the percentage who continue to use a method for 1 year.

dThe percentages becoming pregnant in first year are based on data from populations in which contraception is not

used and from women who cease using contraception to become pregnant. Among such populations, about 89%

become pregnant within 1 year. This estimate was lowered slightly (to 85%) to represent the percentages who

would become pregnant within 1 year among women now relying on reversible methods of contraception if they

abandoned contraception altogether.

eThe ovulation and TwoDay methods are based on evaluation of cervical mucus. The Standard Days method

avoids intercourse on cycle days 8 through 19. The Symptothermal method is a double-check method based on

evaluation of cervical mucus to determine the first fertile day and evaluation of cervical mucus and temperature to

determine the last fertile day.

fFoams, creams, gels, vaginalsuppositories, and vaginal film.

gWith spermicidal cream or jelly.

hWithout spermicides.

iella (ulipristal) is labeled for 120 hours after unprotected intercourse. Plan B One-Step, Next Choice One Dose,

MyWay, Take Action, Aftera, EContra Ez, and After Pill are levonorgestrel products specifically marketed for

emergency contraception. The labeling for these products says to take the pill within 72 hours after unprotected

intercourse. Research has shown that all of the brands listed here are effective when used within 120 hours after

unprotected sex. Research has shown that both pills can be taken at the same time with no decrease in efficacy or

increase in side effects and that they are effective when used within 120 hours after unprotected sex. The Food

and Drug Administration has in addition declared the following 19 brands of oral contraceptives to be safe and

effective for emergency contraception: Ogestrel (one dose is two white pills), Nordette (one dose is four lightorange pills), Cryselle, Levora, Low-Ogestrel, Lo/Ovral, or Quasence (one dose is four white pills), Jolessa, Portia,

Seasonale or Trivora (one dose is four pink pills), Seasonique (one dose is four light-blue-green pills), Enpresse

(one dose is four orange pills), Lessina (one dose is five pink pills), Aviane or LoSeasonique (one dose is five

orange pills), Lutera or Sronyx (one dose is five white pills), and Lybrel (one dose is six yellow pills).

jHowever, to maintain effective protection against pregnancy, another method of contraception must be used as

soon as menstruation resumes, the frequency or duration of breast-feeding is reduced, bottle feeds are introduced,

or the baby reaches 6 months of age.

k$ up to $10/item, $$ up to $50/unit, $$$ up to $80/unit, $$$$ more than $80/unit (These are approximate costs and

may vary based on location of purchase and patient insurance.).

lAdministration or clinic costs not included. Initial cost of product reported but over time similar to $$ cost (e.g.,

injectable MPA 150 mg/mL suspension one syringe approximately $95, but works for 3 months making its monthly

cost similar to COCs or POPs which range from $20 to $45/pack generic, and copper IUD and levonorgestrel IUS

may cost more initially but will work for up to 10 years and 5 years, respectively).

mInitial cost for procedure but over time may be more cost-effective than other products used frequently (e.g.,

monthly contraceptives, condoms, or spermicides).

IUD, intrauterine device; IUS, intrauterine system; LAM, lactational amenorrhea method; MPA,

medroxyprogesterone acetate.

Source: Hatcher RA et al. Contraceptive Technology. 20th ed. New York, NY:Ardent Media; 2011:24, Table 3-2;

includes additional information from www.goodrx.com. Accessed August 25, 2017;

http://americanpregnancy.org/preventing-pregnancy/diaphragm/. Accessed June 11, 2017;

https://www.plannedparenthood.org/learn/birth-control/cervical-cap. Accessed June 11, 2017.

CIGARETTE SMOKING AND USE OF CHCS

S.F. should be strongly encouraged to stop smoking (see Chapter 91, Tobacco Use

and Dependence). Women who are 35 years of age or older and smoke 15 or more

cigarettes/day should not use CHCs as a method of contraception. Although S.F. is

not yet 35, she is smoking one pack/day (20 cigarettes). In her case, many clinicians

would not prescribe CHCs. Although S.F. currently does not have any medical

problems that would preclude her from using CHCs, she should be informed that

CHCs should not be prescribed for her in 2 years if she continues to smoke. In

addition, S.F. should be informed that smoking may decrease fertility and has adverse

effects on birth outcomes, which is important given her plans to start a family in the

near future.

CARDIOVASCULAR DISEASE

An increased risk of cardiovascular death in women who use COCs has been

reported in several studies.

8–11 One study reported that in women who do not smoke

or use COCs, the risk of cardiovascular death is 0.59/100,000 women younger than

35 years and 3.18/100,000 women at least 35 years of age. Among nonsmokers, using

COCs increased the risk to 0.65/100,000 and 6.21/100,000 women younger than 35

years or at least 35 years of age, respectively. For COC users who smoke, the risk is

3.3/100,000 women younger than 35 years and 29.4/100,000 women at least 35 years

of age.

12 The increase in mortality is concentrated in smokers of 35 years and older.

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