Introduction: Welcome to CUGH’s bi-weekly clinical case-series, “Reasoning without Resources,” by Prof. Gerald Paccione of the Albert Einstein College of Medicine. These teaching cases are based on Prof. Paccione’s decades of teaching experience on the medical wards of Kisoro District Hospital in Uganda. They are designed for those practicing in low resource settings, Medicine and Family Medicine residents, and senior medical students interested in clinical global health. Each case is presented in two parts. First comes a case vignette (presenting symptoms, history, basic lab and physical exam findings) along with 6-10 discussion questions that direct clinical reasoning and/or highlight diagnostic issues. Two weeks later CUGH will post detailed instructors notes for the case along with a new case vignette. For a more detailed overview to this case-series and the teaching philosophy behind it, see Introduction to “Reasoning without Resources”. Comments or question may be sent to Prof. Paccione at: [email protected] Note: If you would like to be notified when a new case is posted (along with instructor notes for the previous one), send your e-mail to Jillian Morgan at [email protected] About the Author: Dr. Gerald Paccione is a Professor of Clinical Medicine at the Albert Einstein College of Medicine in the Bronx, New York. His career has centered on medical education for the past 35 years – as a residency Program Director in Primary Care and Social Internal Medicine at Montefiore Hospital, and director of the Global Health Education Alliance at the school. He has served on the Boards of Directors of Doctors for Global Health, Doctors of the World USA, and the Global Health Education Consortium. Dr. Paccione spends about 3 months a year in Uganda working on the Medicine wards of Kisoro District Hospital where he draws examples for the case studies. Gerald Paccione, MD Professor of Clinical Medicine Albert Einstein College of Medicine 110 East 210 St., Bronx, NY 10467 Tel: 718-920-6738 Email: [email protected] 1 CASE 9 – BACK PAIN A 24 year old man, a farmer, was in his usual, fully functional state of health until 3 months ago when he began feeling pain in his lower back and buttocks. The pain would begin at night during sleep, be worse in the morning before going to the fields, and seem better by mid-day. At first, he could dig the rest of the day without problems, but over the past 2 months the pain has gotten gradually worse and he’s felt “hot” and increasingly weak. Getting up and walking around at night helps lessen the pain in the morning. Sometimes the pain is worse in the right buttocks, sometimes in the left. He tried aspirin, which provided some relief, but despite taking more aspirin the pain has increased over the past few weeks such that it’s now too painful to walk at all, and he’s had to stop working. He’s had no other problems like this before, nor has anyone in his family, and no recent rashes, joint swelling or pain, weight loss, abdominal pain, diarrhea, cough or lung problems, weakness in his legs or arms, or problems with his urine. He’s been sexually active with his wife of 3 years, and over the past year when in Kampala with 3 other women, but has not had any sexually-transmitted diseases nor noted a penile discharge. He’s not had any problems with his vision, and he has had only1 episode of “red eyes” (with yellow crusts sealing his eyes in the morning) about 4 months ago, which lasted 2 weeks and went away without treatment (neither wife nor his 2 children had red eye at the time). P.E. Well-nourished muscular young man, walking slowly supported by 2 other men, one on either side. V.S. T: 99 p.o.; BP 100/70; HR 88 and regular; R: 16 Skin/palms/soles: without rash or lesions Eyes: not injected, PERRLA, no photophobia; fundi, normal with flat discs and no exudates Mouth: no thrush or ulcers Neck: no adenopathy, JVP, or thyromegaly Lungs: clear Heart: S1, S2, no murmurs or rubs; Abdomen: no hepato-splenomegaly or tenderness, masses; Rectal: guiuac (-), prostate palpable and soft/boggy, non-tender; Musculo-skeletal: peripheral joints normal, with full range of motion; hands normal without swelling; hips: normal internal and external rotation without pain for the first 30 degrees but pain elicited at the extremes of motion in the buttocks and back bilaterally; palpation: tender to firm palpation with thumb 2-3 cm to right and left of lower LS spine, 3-6 cm below level of iliac crest pelvic compression at iliac crests bilaterally with patient supine: pain in mid-lower back Neurologic: normal mental status, sensory, reflexes, cerebellar; motor normal 5/5 upper extremities, ~ normal motor lower extremities if no/minimal movement during quadriceps/hamstring/psoas evaluations; gait: limited by pain, clutching lower back. U/A (post prostate exam): s.g. 1.025, protein -, blood +2, leuk est +2, nitrates (-), WBC 15-20, RBC 10-20, no casts seen; 2 INSTRUCTOR NOTES What is the “frame” in this case (key clinical features the final diagnosis must be consistent with)? Young male, 24 years old Timing of pain: Insidious onset, chronic, progressive over 3 months Worse in the morning (after rest), better with exercise Pain/difficulty with walking/weight bearing Exam with palpation tenderness lateral to sacrum bilaterally; hip, normal internal/external rotation As with most diagnostic challenges in Medicine there are 2 “levels” of the differential diagnosis in this case: what and where is the pathology, and what’s causing it? What pathologic process is causing this patient’s pain? How do you know? Causes of low back pain (LBP), a very common problem in all populations, are customarily divided into “mechanical” and “inflammatory”. Over 95% of LBP is mechanical: stress/tear of ligaments, facets, or discs - usually characterized by sudden onset, relief by rest or lying supine, worsened by movement or physical work, and transient, with steady improvement over days/weeks. Inflammatory pain is characterized by: insidious onset, gradual improvement with exercise and not rest, and worse at night and in the morning. This patient has inflammatory pain. Where does the pain originate from in this patient? How do you know? The pain originates in the sacroiliac joints between the pelvis and the sacrum. Sacroiliac pain is often vague and diffuse, felt across the lower back and in the buttocks, aggravated by weight-bearing. Walking is painful, and often only possible with bilateral support. Although gait can be affected in “mechanical” causes of LBP by muscle spasm or sciatic nerve impingement, standing/weight-bearing in these other more common conditions is relatively painless. In this patient, pain was felt in the buttocks bilaterally, frequently alternating in severity between sides. Firm palpation over the SI joints elicited tenderness, as did medial compression of the pelvis at the iliac crests which elicited pain over the compressed (inflamed) SI synchondrosis. Internal and external rotation of the hips were normal up to the extremes of movement (which torques the SI joints), signifying non-inflamed hips. What other exam maneuvers can help localize the origin of LBP to this area? Have patient lie on his side with lower leg extended and top leg flexed at both the hip and the knee 90 degrees: with the palm of your hand, jab the flexed kneecap in the direction of the femur. If the SI joint is inflamed, sudden pain should be felt in the mid-back. Have the patient lie supine with hip and knee again flexed 90 degrees: press down over the kneecap with force. If the SI joint is inflamed, pain should be felt in the mid-back. Have the patient lie prone: If the SI joint is inflamed, pressure on the lower spine should induce pain over the SI joints. 3 With the patient lying prone, hold the pelvis at the iliac crests bilaterally, and with alternating movements, vertically lift and press down each side in a rocking sequence. If the SI joint is inflamed, pain should be localized to the SI joint area. What are the most common misdiagnoses made by novice diagnosticians in this type of presentation? Hip arthritis: especially if unilateral, sacroiliitis is often misdiagnosed as “hip arthritis” (possibly septic hip arthritis if the patient is young) due to its vague localization around the back-buttock-hip and the inability to weight bear; Mechanical back pain/herniated disc: common things are common, farmers who bend, carry and dig all day can have back pain, and most novice clinicians have never seen full-blown sacroiliitis. So conflicting data is either not elicited (e.g. close-ended questions used and misinterpreted, appropriate exam maneuvers not done) or the unexpected is ignored because it’s too dissonant. “Forcing” diagnoses into familiar patterns and distorting observations to fit the known or comfortable is a common cognitive error. Thus, at the end of the history and physical exam, we conclude that this patient has a chronic bilateral inflammatory sacroiliitis. What is the differential diagnosis of this condition in the West (i.e. specific etiologies)? How does the differential differ between the developed “West” and Sub-Saharan Africa? In both the U.S. and Africa this patient would be considered to have the axial version (i.e. sacroiliitis, SI) of the “spondyloarthritis” (SpA) family of diseases, which share certain clinical features: namely, inflammation of the axial joints (SI), asymmetric oligoarthritis, and enthesitis (inflammation of the ligamentous or tendon attachment to bone), with possibly additional extraarticular manifestations in the eye, skin, genitals, and gut. In the West, the relevant family of diseases that causes sacroiliitis bears a strong association with (HLA) B27. It’s comprised of the following diagnoses: Undifferentiated spondyloarthritis (USpA) Ankylosing spondylitis (AS) Reactive arthritis (ReA) (formerly Reiter syndrome) SpA associated with Psoriasis SpA associated with Inflammatory Bowel Disease (Crohn and ulcerative colitis) Juvenile onset spondyloarthritis The estimated prevalence of SpA in a Caucasian population is 0.5-2%, with the vast majority being classified as USpA or ankylosing spondylitis. The term USpA is used to refer to patients with inflammatory back pain who do not meet the more specific criteria of the other disease subsets in the SpA family, e.g. not ankylosing spondylitis because of the absence of radiologic evidence for AS; not ReA because of the absence of a definite infection causing diarrhea or urethritis within 4 weeks before the arthritis developed). Reactive arthritis (prevalence of 0.1% in the West, much less frequent than AS or USpA) is thought to be an immune-mediated synovitis from slow bacterial infections that remain viable but 4 elusive, and produce antigens that cause persistent inflammation. There are over 30 microbes implicated but the best-defined agents of ReA are Chlamydia trachomatous urethritis (and pneumonia), and the bowel pathogens salmonella, campylobacter, shigella, and yersinia. The HLA B27 allele is thought to confer increased propensity for microbe survival in the synovium and elsewhere, and/or for ongoing inflammation in the synovium. The literature is confusing because the diseases are overlapping, long-term follow-up often leads to more specific diagnoses as other manifestations appear, 30-40% of infections associated with Reactive Arthritis are asymptomatic, and the list of causative organisms implicated in ReA continues to grow and can’t be reasonably investigated anywhere. In Africa, the differential diagnosis of SpA is influenced by the following observations: a) HLA B27 is almost non-existent, and consequently ankylosing spondylitis and reactive arthritis with extraarticular manifestations (Reiter syndrome) were thought to be rare (although perhaps not as rare as clinical research in Africa!); b) HIV has changed that: reactive arthritis and USpA, although often atypical, are now commonly found in areas affected by HIV. In the absence of HLA B27, HIV may serve to either facilitate microbe persistence and/or ongoing inflammation in inducing a “reactive arthritis”, or be the cause of the ReA itself; c) other infections endemic in Africa can cause chronic inflammatory disease of the SI joint in young people, particularly TB and Brucella. d) lack of diagnostic tests and X-rays make the application of Western diagnostic criteria for the various forms of SpA that much more difficult. What are the most useful diagnostic clinical criteria to apply to this condition in Africa? The European Spondyloarthritis Study Group’s (ESSG) are clinical, and do not rely on tests, like HLA B27 or MRI/X-rays that are unavailable in Africa. According to the ESSG criteria, to be classified with SpA, a patient has to satisfy ONE of two entry criteria: “inflammatory” back pain (i.e. 4 of 5 of: age of onset <40, insidious onset, chronic for >3 months, morning stiffness, improvement with exercise) OR synovitis that is either asymmetric or predominantly in the legs (warm, swollen soft tissue, effusion, decreased active and passive range of motion, worse after rest). PLUS ONE additional criterion: (+) family history; urethritis, cervicitis, or acute diarrhea within one month before arthritis; buttock pain alternating between buttocks; enthesopathy; psoriasis; inflammatory bowel disease; X-ray sacroiliitis. The Amor criteria add “points” for other clinical features: sausage-like toe or digit, heel pain, iritis, response to NSAIDS within 48 hours or recurrence within 48 hours of discontinuation. 5 What common diseases are eliminated from diagnostic consideration in this case by the timing criteria, i.e. chronicity and onset of disease? How frequently are the various clinical features associated with this disorder actually seen in patients with it? (N.B. Sensitivity (Se), % patients with SpA with the finding; Specificity (Sp), % of non-SpA without the finding; Likelihood ratio (LR), odds that a given test result came from someone with as opposed to without SpA) The chronicity and onset criteria exclude from the differential diagnosis of SpA other causes of infectious arthritis or sacroiliitis such as pyogenic staph infections (in IVDUs), gonococcal arthritis, viral arthritides, and most spirochetal/borrelial infections. As diagnostic tests, the accuracy of the various clinical features seen in chronic back pain due to SpA are: (Data from Rudwaleit, M, et al AnnRheum Dis 2006; 65:1251-2; and Amor, B Rheum DisClin of N.Am 1998 24: 677-695) Inflammatory type of back pain: Se 75%; Sp 76%; LR+ 3.1, LR- 0.33 Asymmetric oligoarthritis of lower limbs: Se: 40-45%, Sp: 85-95%, LR+4, LR- .67 Sausage Digit (dactylitis: tendinitis of finger): Se 20-25%, Sp 95-99, LR+ 4.5; Heel pain (enthesitis, swelling on sides of Achilles tendon): Se 30-40%, Sp 90%, LR+3.4 Eye: Conjunctivitis: Se, 35%; iritis: Se, 5-20%, Sp 97%; LR+ 7.3, LR- 0.8 (+) F.Hx. for similar issues: Se 30%, Sp 95%; LR+6.4, LR- 0.7 Skin: keratoderma b. Se 5-30%; circinate balanitis Se 20-40%; oral ulcers (painless) Se 5-10%; ESR elevated: Se 50%, Sp 80%, LR+2.5, LR- 0.6 Response to NSAIDS within 48 hrs: Se 75-80%, Sp 85%; LR+ 5.1, LR- 0.27 How would you diagnose/classify his illness? Explain. What is the significance of him being African? This patient has chronic sacroiliitis. By ESSG criteria, he meets one entry criteria for SpA, inflammatory type back pain (5 of 5 items), and one additional criterion, bilateral buttuck pain. He fits no additional criteria for a more specific diagnosis at this time, so his disease would be classified USpA at this point. Of note, his prostate is soft and boggy, and his urinalysis is abnormal: prostatitis is commonly seen in reactive arthritis due to Chlamydia (80%), and even as part of the general immune response in ReA due to enteric organisms, but is not one of the official “criteria” for SpA nor ReA. Neither is a history of “conjunctivitis”, which this patient had (by history) around the time of the onset of back pain, a criterion for SpA. Although conjunctivitis is common in ReA, it’s too non-specific to carry much diagnostic weight (despite, in his case, no one else in his family having “red-eye” at the time, a very contagious disease when due to common infection). Iritis, on the other hand, is a ReA/SpA criterion due to its greater specificity. This case illustrates a good example of why criteria created for and useful in research, may not translate clinically: these features of this patient’s history, although suggestive of ReA, don’t count “officially”. 6 Although an X-ray of the SI joints may be possible in rural Africa, it’s unlikely to be abnormal: it takes years of inflammation to show evidence of SI on a plain X-ray. It’s most likely that this man has a form of reactive arthritis presenting as an axial SpA that we cannot further specify etiologically for lack of advanced tests e.g. synovial culture or PCR identification of organisms – with one exception: HIV, for which we can test. Although this patient could have acquired Chlamydia during his sexual exploits in Kampala, it’s also quite possible that he acquired HIV. The rarity of HLA B27 in Africans makes it more likely that HIV is present, either facilitating the progression of chlamydial disease to ReA or itself causing the ReA symptoms. (In Caucasions, Chlamydia induces ReA in only ~ 1-5% of cases (of Chlamydial infection), and HLA B27 is the major risk factor.) TB, Brucella and typhoid, all more commonly seen in Africa, are unlikely to be causing sacroiliitis in this patient. All of these infections would usually be associated with significant additional symptoms (e.g. fever, weight loss and possibly cough) often antedating the back pain, and the associated sacroiliitis would likely be unilateral. Although late-stage HIV also causes constitutional symptoms and wasting, the immune manifestations of HIV commonly occur before this, and indeed symptoms of ReA often resolve as the disease progresses. What further diagnostic tests would be warranted in this patient in rural Africa? HIV Empiric trial of NSAIDS (can be used as a diagnostic test for SpA, and therapy) Plain film of SI joint: unlikely to be abnormal or to change diagnostic impression ESR: unlikely to influence diagnosis (risk is that it will be misinterpreted as indicating no SpA if normal (50% chance)) What is the appropriate treatment and prognosis for this patient? Therapy in chronic SpA has been disappointing, and in Africa is largely restricted to NSAIDs. Although persistent microbial antigens or organisms are thought to be the basis of ReA, antibiotic therapy has been disappointing: it doesn’t work in enteric ReA, nor in chronic urogenital ReA. In acute urogenital ReA (i.e. the first presentation of arthritis within the past 6 months, with initial onset of disease within 4 weeks of urethritis) anti-chlamydial antibiotics decrease the duration of symptoms and the likelihood of recurrent arthritis, although do not influence long-term prognosis. Since this patient did not have defined urethritis, he does not exactly fit that picture. Nevertheless, treatment of both he and his sexual contacts for Chlamydia makes good public health sense, and prolonged therapy (for acute chlamydial ReA) could be warranted despite the paucity of evidence that it will help his sacroiliitis. If the patient is HIV+, consideration should be given to treating HIV independent of his CD4 count if NSAIDs are insufficient to control the activity of the sacroiliitis. Prognosis is very difficult to assess in SpA with its multiple etiologies and overlapping syndromic classifications. In general, 30-50% recover, 20-40% recur, and 30-50% develop chronic disease or symptoms. Reactive arthritis in patients with HIV tends to run a more aggressive course with extraarticular manifestations, but the data are sparse. Our patient was HIV (+). 7 Suggested Readings: Rudwaleit, M. et al; Easy assessment of axial spondyloarthritis (early ankylosing spondylitis) at the bedside Ann Rheum Dis 2006; 65:1251-12 Njobvu P, McGill, P; Human Immunodeficiency Virus Related Reactive Arthritis in Zambia J Rheumatol 2005; 32:1299-304 Colmegna, I; et al. HLA-B-27-Assocaiated Reactive Arthritis: Pathogenetic and Clinical Considerations Clinical Microbiol Rev 2004; 17(2):348 – 360 Carter, J.D., et al. Chlamydiae as Etiologic Agents for Chronic Undifferentiated Spondyloarthritis Atrhitis Rheum. 2009; 60 (5): 1311-16 UpToDate; Yu, D.T. Undifferentiated spondyloarthritis: Clinical Manifestations, definition and diagnosis _________________________________ CASE_9_Back_Pain_INSTRUCTOR_NOTES_FINAL 8