Course Case Studies

Autoimmune Diseases

Course #94453 - $75 • 15 Hours/Credits

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Learning Tools - Case Studies


Patient A is a woman, 25 years of age, who recently gave birth to her second child. She visits her primary care provider because of the gradual onset of fatigue, anxiety, and a feeling of her "heart pounding." The physician finds nothing remarkable on physical examination; a CBC indicates slight anemia. The physician tells her he believes the symptoms are related to slight anemia and the stress of giving birth in addition to caring for a toddler. The physician recommends that Patient A try to rest more, take a daily multivitamin with iron, and obtain some help caring for her two small children.

Over the next year, Patient A's symptoms wax and wane. Her family is supportive as she tries to reduce the stress in her life, but her symptoms do not resolve completely. At a routine physician office visit, she describes continued extreme fatigue as well as muscle weakness. On physical examination, her skin feels warm and moist and her pulse is slightly elevated (80 beats per minute). During the history-taking, the physician learns that Patient A's mother has Graves disease. On further physical examination, the physician notes that the thyroid gland feels normal, that her eyes and eyelids appear normal, and that she has no fine finger tremor. However, based on the family history and Patient A's desire to have another child in the near future, the physician orders thyroid function studies. The TSH level is normal, as are the T3 and T4 levels. The physician reiterates the need for lifestyle modifications, including enhanced nutrition, exercise, better sleep, and over-the-counter analgesics as needed.

Rationale and comments: Several factors indicate the possibility of Graves disease, although some do not. Patient A is younger than the typical woman in whom Graves disease first occurs (40 to 60 years). But in individuals with genetic susceptibility, stress and recent childbirth have been identified as potential environmental triggers for the disease. Her symptoms of fatigue, anxiety, and palpitations are among the common symptoms of Graves disease, as is her warm, moist skin. However, the lack of thyroid enlargement, a pulse of less than 90 beats per minute, and the absence of finger tremor are findings with the most significance in ruling out hyperthyroidism.

It seems appropriate to rule out a diagnosis of Graves disease given that Patient A wants to have another child. The American Association of Clinical Endocrinologists recommends TSH with measurement of total T4 or a free T4 index testing for women of childbearing age before or during pregnancy. Laboratory testing confirmed that she did not have Graves disease, as a low TSH level with increased T4 levels indicates hyperthyroidism.

Patient A's symptoms continue, and she becomes increasingly frustrated by the lack of symptomatic relief. Among the new symptoms that have developed are dry eyes, intermittent headaches, and pain in the finger joints of both hands, all of which she attributes to too much time working on the computer at her job. The pain in her fingers resolves with rest. She also begins to have occasional pain and stiffness in both hips, especially in the morning. She starts to take large doses of over-the-counter analgesics as well as nutritional supplements. She continues to feel fatigue so overwhelming that she must call in sick to work at least once or twice every month. She wants to have another child but does not feel as though she would be able to physically handle a pregnancy and the care of a third child. She begins to have mood swings, and she feels depressed "sometimes." She makes an appointment with her primary care provider to discuss her increasing symptoms. Based on her description of new symptoms, the physician orders a rheumatoid factor test, and the result is a low positive. He refers her to a rheumatologist for possible rheumatoid arthritis.

On examining Patient A, the rheumatologist finds normal vital signs, except for a low-grade fever. There is slight limitation in the range of motion of both hips, with some decreased muscle strength in the left leg. In taking the history, the rheumatologist learns that Patient A's joint pain has been present for about one month and that her pain/stiffness in the hip lasts for about 30 to 60 minutes each morning. The physician orders a CBC, platelet count, ACPA, ESR, and CRP; the results of all are normal, except for continued slight anemia. Radiographs of the hips show slight degeneration in the left hip. The rheumatologist tells Patient A that her pain may be related to early osteoarthritis, and he prescribes a COX-2 inhibitor for pain relief, prescribes an antidepressant, and recommends regular exercise, more rest, and counseling for stress reduction. Patient A interprets the suggestion of counseling and an antidepressant as meaning that her physical symptoms are "in her head," and she becomes even more frustrated.

Rationale and comments: Again, some of the details of Patient A's case fit with a diagnosis of rheumatoid arthritis and others do not. The proximal interphalangeal and metacarpophalangeal joints are among the most commonly involved joints, and they are not usually painful at rest. Joint symptoms are usually bilateral. As is the case for most individuals, the symptoms of rheumatoid arthritis develop over a long period of time (weeks to months). Her other symptomsfatigue, weakness, and generalized muscular achesare also suggestive of rheumatoid arthritis. Approximately 46% of individuals with rheumatoid arthritis have extra-articular manifestations, and among the most common are dry eye syndrome and anemia of chronic disease. Depression is also common, occurring in about one-third of individuals. In addition, the findings of a low-grade fever, limitation in the range of motion of the hip, and decreased muscle strength near an affected joint are consistent with rheumatoid arthritis.

The positive rheumatoid factor would also seem to suggest rheumatoid arthritis, as this finding has long been known as an indicator of rheumatoid arthritis, and studies have shown that it is positive in approximately 69% to 90% of people with the disease. However, the test may be positive in healthy individuals as well as in individuals with other rheumatic diseases (e.g., Sjögren syndrome, systemic sclerosis, systemic lupus), with chronic infections, or with pulmonary disease. The 2010 ACR/EULAR classification criteria for rheumatoid arthritis call for a rheumatoid factor as well as an ACPA, which has a higher specificity. The negative ACPA and normal ESR and CRP level, along with her other signs and symptoms, yield a score of 5 on the diagnostic criteria, one point lower than the 6 needed for a diagnosis of "definite" rheumatoid arthritis. The radiographic evidence of degeneration in the left hip and the morning stiffness that lasts less than one hour suggest osteoarthritis.

The rheumatologist's treatment plan is appropriate. There is good evidence that nonselective NSAIDs and COX-2 inhibitors have comparable efficacy, and a COX-2 inhibitor has been associated with lower risks of gastrointestinal adverse events than a nonselective NSAID plus a proton-pump inhibitor. The recommendations for nonpharmacologic treatment are also in line with established recommendations.

Patient A adheres to her medication treatment, and the pain in her hips is somewhat relieved. However, more new symptoms appear over the course of the next year. During the winter, she becomes intolerant to cold weather, with her hands and feet becoming painful and discolored when she is exposed to cold. When she sees her primary care provider, he tells her that she may have Raynaud phenomenon. Her other symptoms continue, and he reiterates the need for her to continue with the rheumatologist's treatment plan. The following summer, she has a strange red, raised rash on her cheeks after being out in the sun. In addition, small, raised sores begin to develop on her legs and arms. The joint pain, swelling, and fatigue continue. She returns to her primary care provider who is himself frustrated by Patient A's continuing symptoms. He suggests that she return to the rheumatologist, but she says she did not have a good experience with him and wants to see a different rheumatologist. He refers her to another local rheumatologist and notes in her chart that she has been a "chronic complainer."

At the first visit, the new rheumatologist elicits Patient A's long medical history and description of her numerous symptoms. On physical examination, the vital signs are normal, except for a low-grade fever. The physician notices small ulcers in her mouth, pain and swelling in both hips, and a slight pleural rub. He orders a CBC and platelet count, an ANA titer, an anti-double-stranded DNA titer, and antiphospholipid antibodies. He also obtains biopsy samples from the lesions on her legs. The results of the lab work show a normal white blood cell count, a low platelet count (<100,000/mm3), and positive ANA titer, anti-double-stranded DNA titer, and antiphospholipid antibodies. The findings of the skin biopsy indicate small vessel vasculitis. The rheumatologist diagnoses systemic lupus erythematosus, explaining to Patient A that all of her symptoms over the past four years can be attributed to the disease.

Rationale and comments: Patient A's constellation of symptoms indicates systemic lupus. The classic sign of a butterfly-shaped rash in the malar area of the face is present in up to 90% of cases. Other common symptoms include the discoid rash elsewhere on the body, photosensitivity, Raynaud phenomenon, joint pain (especially in proximal joints of the fingers), fatigue, dry eye syndrome, low-grade fever, small oral ulcers, pain and swelling in both hips, and slight pleural rub. The ANA titer is highly sensitive for systemic lupus, with a positive result in approximately 93% to 100% of individuals with the disease. An anti-double-stranded DNA test can help confirm a diagnosis of systemic lupus, as it has greater specificity than the ANA titer. About 20% to 30% of people with systemic lupus have antiphospholipid antibodies, which increases the risk for thromboembolism and pregnancy loss. The clinical findings, coupled with the results of laboratory testing, fulfill nine of the 11 criteria for the diagnosis of systemic lupus; four criteria are needed for a definite diagnosis.

The rheumatologist emphasizes the need for both pharmacologic and nonpharmacologic measures. He begins treatment with hydroxychloroquine (200 mg PO) twice daily and 5 mg of prednisone daily, after obtaining baseline dual x-ray absorptiometry, measuring her height, and determining the serum 25-hydroxyvitamin D level. The rheumatologist also makes several recommendations:

  • Use artificial tear drops.

  • Take supplemental calcium and vitamin D.

  • Engage in regular exercise.

  • Schedule a comprehensive eye examination.

  • Schedule routine gynecologic examinations.

  • Modify lifestyle factors to reduce the risk of cardiovascular disease.

  • Protect skin against exposure to ultraviolet rays.

  • Maintain follow-up visits at six-month intervals.

He also warns her of the risk of pregnancy loss related to the presence of antiphospholipid antibodies and encourages her to learn all she can about the disease, providing her with educational materials, a list of reliable websites, and a list of local support groups.

Rationale and comments: The rheumatologist's treatment and follow-up plan meet all the recommendations in established guidelines. The preferred first-line treatment of systemic lupus without major organ involvement is an antimalarial drug and a low-dose glucocorticoid (usually prednisone), two of only three drugs approved by the FDA for use in systemic lupus. Antimalarial agents offer many benefits. They can alleviate joint-related, cutaneous, constitutional, and serosal manifestations of systemic lupus; they can prevent disease flares; they are well tolerated; they have been associated with a lower risk of infection than other treatment approaches; and they have a protective effect on survival. Artificial tear drops are recommended for the treatment of mild dry eye syndrome related to systemic lupus. Glucocorticoid-induced osteoporosis occurs in 4% to 24% of individuals with systemic lupus, and the ACR recommends a daily calcium intake of 1,200 to 1,500 mg and supplemental vitamin D, as well as a baseline dual x-ray absorptiometry, height, and serum 25-hydroxyvitamin D level. Hydroxychloroquine increases the risk for retinopathy, although this side effect is rare at Patient A's dose. Still, ophthalmologic follow-up is important, and the American Academy of Ophthalmology recommends a complete ophthalmologic examination within the first year after treatment. Systemic lupus is associated with an increased risk for HPV infection and cervical dysplasia, making it necessary to have regular gynecologic evaluations. In addition, the risk of cardiovascular disease is increased, and steps should be taken to reduce the risk. Lastly, systemic lupus is associated with an increased risk for other autoimmune diseases, and healthcare professionals should carefully consider the possibility of these diseases during follow-up. Providing educational resources in a variety of formats helps to ensure that patients better understand their disease and its management, which is an essential component in the treatment of a chronic disorder.

Over the next month, Patient A's rash gradually resolves, and her pain and fatigue improve. She feels well enough to comply better with an exercise program, and her symptoms further improve. Her rheumatologist sees her for follow-up every six months. One year after the initiation of treatment, she continues to feel much better than she "has in a long time" and has made several new friends in her local support group.

Rationale and comments: This case reflects the challenges in diagnosing an autoimmune disease because of vague, overlapping symptoms. The absence of characteristic features on physical examination does not necessarily rule out an autoimmune disease, because signs and symptoms tend to wax and wane. As was the situation for Patient A, most individuals consult many healthcare providers, often over the course of several years, before a diagnosis is made. In addition, the attitudes of Patient A's physicians represent a common reaction. More than 45% of individuals with an autoimmune disease have reported that they had been labeled as a chronic complainer in the early stages of their disease because no cause for their symptoms could be determined.

  • Back to Course Home
  • Participation Instructions
    • Review the course material online or in print.
    • Complete the course evaluation.
    • Review your Transcript to view and print your Certificate of Completion. Your date of completion will be the date (Pacific Time) the course was electronically submitted for credit, with no exceptions. Partial credit is not available.