St. John \200\231s wort (Hypericum perforatum) \200 St. John \200\231s wort has been show n in relatively robust trials to improve mild depression. This may relate to its effect on inhibiting synaptosomal uptake of 5-HT, d opamine, normetanephrine, glutamate, and GABA. Response in patients with arthritis or chronic pain may be due to improvements in mood, pai n perception or coping strategies. St. John \200\231s wort increases the activity of cytochrome P450 3A4, which is responsible for the metabolism of many drugs. Concomitant administration results in decr eased serum levels of cyclosporine and digoxin. St. John \200\231s Wort also decreases the anticoagulant effect of warfarin, and patients may require dose adjustment as a result. Gamma linoleic acid (GLA) \200 GLA is a plant-seed-oil derived, unsaturated fatty acid th at suppresses production of Il-1 B . It is contained in many different plant-seed oils (e.g ., black currant-seed oil). Compared with placebo, 2.8 g/d GLA signi \201 cantly improves symptoms and signs of active RA over 6 months. 2 However, virtually all plant- seed oil preparations that contain GLA a re often taken at lower daily doses than those shown to be effective. Devil \200\231s Claw (Harpagophytum procumbens) \200 This may work by inhibiting cyclooxy genase or iNO synthase in joint tissues or by suppressing matrix metalloproteinase production. At 60 \200\223100 mg/day, Harpagophytum extract (harpagoside) has moderate but signi \201 cant effects on back and joint pain associated with OA. 3 1 Soeken KL, Miller SA, Ernst E. Herbal medicines for the treatment of Rheumatoid arthritis : a systematic review. Rheumatology 2003; 42(5): 652 \200\2239. 2 Zurier RB, Rossetti RG, J acobson EW et al. Gamma-linolenic acid treatment of rheumatoid arthri- tis. A randomized pl acebo-controlled trial. Arthitis Rheum 1996; 39: 1808 \200\22317. 3 Gagnier JJ, Chrubasik S , Manheimer E. Harpgophytum procumbens for osteo-carthritis and low back pain: a systematic review. BMC complement Altern Med 2004; 4: 13 \200\22323. CHAPTER 21 Complementary and alternative medicine 556 Physical and hands-on therapies Acupuncture \200 Acupuncture is commonly used to treat ne ck and back pain and is easily incorporated into primary care consultations. Meta-analyzes suggest short-term ef \201 cacy for low back pain 1 but no overall effect for neck pain. 2 Controversy exists among acupuncturists as to the adequacy of acupuncture techniques used f or back pain in published trials. No convincing evidence exists to suggest acupuncture should be used for long-term relief of symptoms in OA or RA. Serious complications of acupuncture exist (e.g., pneumothorax, hepatitis B, spinal cord injury, infection) but are rare. Complications may be underreporte d. 3, 4 Tai Chi \200 In RA, tai chi has been shown to increase plantar \202 exion range and is associated with a higher level of participant enjoyment. Trials have shown few bene \201 ts in terms of outcome measures. It appears not to exacerb ate RA, 5 and may help with \201 bromyalgia. Re \202 exology \200 This is one of the most frequently used CAMs. \200 From the few c ontrolled trials taken together, results do not suggest there is any speci \201 c therapeutic effect. Spinal manipulation \200 Of the most rigorous sham-controlled studies of manipulation (fo r any indication of back pain), none showed bene \201 t compared with placebo. \200 Stud ies suggest that about 50% of patients have side effects, although these are chie \202 y mild or transient. 6, 7 Reliable estimates of the incidence of serious adverse effects do not exist. Reported effec ts include vertebral arterial dissection, strokes, disc herniation, spinal fracture, cauda equina syndrome and worsening of undisclosed spinal in \202 ammatory conditions (e.g., AS/ SpA, discitis). Reports from neurologists suggest serious neurological lesions occurring after neck chiropractic are not infrequent. There is concern over excess radiation risk from overuse of radiographs ordered by practitioners. 1 Ernst E, White AR. Acupuncture for backpain: a meta-analysis of randomized controlled tri als. Arch Intern Med 1998 ; 158: 2235 \200\22341. 2 White AR, Ernst E. A systematic review of randomized controlled trials of acupuncture for neck pain. Rheumatology 1999; 38: 143 \200\2237. 3 Ernst E, White AR. Life-threatening adverse reactions after acupuncture? A sys tematic review. Pain 1998; 71: 123 \200\2236. 4 Ernst E. Acupuncture \200\224a critical app raisal. J Intern Med 2006; 259(2): 125 \200\22337. 5 The Cochrane library. Issue 4. 2004. 6 Ernst E. Prospective investigations into the safety of spinal manipulation. J Pain Symptom Manage 2001; 21: 238 \200\22342. 7 Ernst E, Canter PH. A Systematic review of systematic r eviews of spirial manipulation. J R Soc Med 2006; 99(4): 192 \200\2236. HOMEOPATHY 557 Homeopathy Homeopathy stems from the belief that tiny quantities of substances have a holis tic therapeutic effect. There has been a great publicized debate about whether homeopathy i s genuinely more effective than placebo, and whether conventional randomized studies are a relevant way of evaluating its effect. Reports in the medical and scienti \201 c literatur e invariably gener- ate prolonged and sometimes \201 erce debate in the letters-to-the-ed itor pages for some time afterwards! Nevertheless, homeopaths are among the most frequently visited CAM practitioners by patients with arthritis. \200 Meta-analyzes of therapeutic trials suggest the clinical effects of homeopathic remedies cannot be fully explained by placebo effects alone. 1 However, the mos t robust methodological studies do not show any positive effects compared to placebo. 2 , 3 There is some evidence that short-term improvement in RA symptoms is superior to placebo. 4 A more robust methodological study, however, suggested no symptomatic improvement in RA ov er 3 months in patients stabilized on DMARDs and NSAIDs. 5 Summarizing four RCTs of homeopathy use in OA, there appears to be a positive effect, altho ugh \201 rm conclusions cannot be reached. 6 \200 One of the most frequently used homeo pathic remedies is Arnica montana . A systematic review of its effects 7 suggests there is no proof of its effect. Preparations of Echinacea are believed by some to have signi \201 cant immunomodulatory properties. Although this is a traditional treatment for a variety of ailm ents, some CAM practitioners advise that patients with autoimmune diseases avoid this suppl ement. 1 Linde K, Melchart D. Randomized controlled trials of individualized homeopathy: a state-o f-the- art review. J Altern Complement Med 1998; 4: 371 \200\22388. 2 Ernst E, Pittler MH. Ef \201 cacy of homeopathic arnica: a systematic review of placebo-controlled clinical tri als. Arch Surg 1998; 133: 1187 \200\22390. 3 Ernst E. Are highly dilute homeopathic remedie s placebos? Perfusion 1998; 1: 291 \200\2232. 4 Jonas WB, Linde K, Ramirez G. Homeopathy an d rheumatic disease. Rheum Dis Clin 2000; 26: 117 \200\22323. 5 Fisher P, Scott DL. A rando mized controlled trial of homeopathy in rheumatoid arthritis. Rheumatology 2001; 40: 1052 \200\2235. 6 Long L, Ernst E. Homeopathic remedies for the treatment of osteoarthritis: a s ystematic review. Br Homeopath J 2001; 90: 37 \200\22343. 7 Ernst E, Pittler MH. Ef \201 c acy of homeopathic arnica: a systematic review of placebo-controlled clinical trials. Arch Surg 1998; 133: 1187 \200\22390. CHAPTER 21 Complementary and alternative medicine 558 Other CAMs Magnet therapy \200 In one randomized study, patients wearing a magnet bracele t experienced reduction of hip and knee pain associated with osteoarthritis when compared t o patients wearing dummy bracelets. 1 \200 Other studies have indicated that magnets may relieve some forms of musculoskeletal pain, although this is controversial. Dietary supplements \200 Glucosamine and chondroitin sulfate supplements have long been u sed for the treatment of osteoarthritis, but the results of clinical trials have been mixed , and its use is falling out of favor. 2 Curcumin (turmeric) has anti-in \202 ammatory properties, and may have some bene \201 cial effects on arthritis. Other commonly used supplements by patients with arthritis and pain include cod liver oil, \201 sh oil tablets, vitamins, and selenium. \200 Although there is little available scienti \201 c evidence to support any recommendations regarding dietary modi \201 cation, this form of intervention remains popular. Hypnotherapy \200 This is of long-standing interest in controlling pain. \200 In studie s, hypnotherapy has been shown to be effective at controlling anxiety. There is some evidence for ef \201 cacy in \201 bromyalgia patients. Stress management/relaxation therapy \200 Stress has been associated with an increased ri sk of sudden death, delay in wound healing, and higher rates of infection. Yoga, acupuncture, and meditation may improve quality of sleep, and decrease perceived stress, fatigue, and depression. Various studies suggest short-term bene \201 t for patients with RA but proof of effects o n measures of disease in the long term are absent. Methodological de \201 ciencies in studies and absence of cost- effectiveness data suggest no \201 rm conclusion can be drawn about the role of therapy i n speci \201 c individuals or disease groups. Spiritual healing \200 A \200\234therapeutic experience \200\235 transmitted by a therap ist \200\231s touch, nontouch, prayer or \200\234mental healing. \200\235 Examples include therapeutic touch, reiki, distance healing, and intercessional prayer. 1 Harlowe T et al. Randomized controlled trial of magnetic bracelets for relieving pain of osteoar- thritis in the hip and knee. BMJ 2004; 18: 1450 \200\2234 2 Clegg DO et al. Glucos amine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N E ngl J Med 2006; 354: 795 \200\223808. OTHER CAMS 559 There is some evidence that \200\234therapeutic touch \200\235 done by nurses can reduce a nxiety in hospital patients. No data exist that compare this to talking to/informing patien ts about their condition. Other \200 Electrical stimulation increases grip strength in RA patients with hand muscle atrophy. Pulsed electrical stimulation can help knee OA symptoms. Data is weake r for an effect on pain from neck OA. Thermotherapy for RA \200\224including wax and Faradic baths, hot and ice packs \200\224have brief positive effects without any harmful effects. 1 \200 Balneothera py may be effective for the treatment of RA and low back pain. 2 Trial methodology has been poor, however \200\224trials have generally not stu died relevant outcomes. Rol \201 ng, a form of deep tissue massage that attempts to stretch and open the fascia, m ay also bene \201 t some patients with arthritis and chronic pain. Further information \200 National Center for Complementary and Alternative Medicine (NCCAM): http://nccam.nih.gov MD Anderson Complementary/Integrative Medicine: http://www. mdanderson.org/departments/CIMER Arthritis Foundation \200\224 Arthritis Today Supplement Guide: http://www. arthritis.org/at-supplement-guide.php Mayo Clinic: \200\234Take a break to meditate \200\235: http://mayoclinic.com/health/ meditation/MM00623 1 Robinson VA, et al . Thermotherapy for treating rheumatoid arthritis. Cochrane Database o f Systematic Reviews 2001, Issue 4. Art. No.: CD002826 2 Pittler MH, Karagulle MZ, Karagull e M, Ernst E. Spa therapy and balneotherapy for treating low back pain: meta-analysis of ra ndomized trials. Rheumatology 2006; 45: 880 \200\2234. This page intentionally left blank 561 Chapter 22 Rheumatologic emergencies Septic arthritis 562 Infections in patients taking anti-TNF- A drugs 566 Acute SLE 568 Syst emic vasculitis 574 Scleroderma crises 574 Methotrexate-induced pneumonitis 576 For vertebral fracture, see Chapter 20 . CHAPTER 22 Rheumatologic emergencies 562 562 Septic arthritis Infection in a joint can progress rapidly and cause destruction of tissues and permanent deformity and disability. When septic arthritis is suspected, investigations should be prompt, appropriate antibiotics should be started without delay, and, where feas ible, infected tissue should be removed. The epidemiology of infections is discussed in Cha pter 17. Suspecting infection \200 Septic arthritis is uncommon but is more likely to occur in patients with established joint disease, with prosthetic joints, or with co-morbidities suc h as diabetes, chronic renal disease, or immunosuppression. Patients \200\224especially the elderly \200\224may not appear systemically unwell. The main differential diagnosis in adults is crystalline arthritis (see Chapter 15). Staphylococcal and streptococcal infections are the most common; septic arthritis from H. in \202 uenzae type b is no longer seen due to vaccinatio ns. Gonococci cause almost 30% of cases in children >11 years. Immediate management of adult joint sepsis (see Table 22.1) \200 Immobilize the joint and provide adequate analgesia. \200 Take blood for CBC, CMP, ESR, CRP, and cultures. \200 Manage sepsis as appropriate and rule out infective endocarditis (especially in IV drug us er (IVDU) or in those with known cardiac valve disease). Drain the joint completely (use at least an 18-gauge needle, since the \202 uid is viscous) and send the sample of joint \202 uid for Gram stain, culture, and for polarized light microscopy (LM). If the polarized LM demonstrates evidence of crys tals and cultures are negative after 48 hours, then consider a diagnosis of a crystaline ar thropathy. \200 If minimal \202 uid is obtained, it should be sent for culture, since identi \201 cation of an organism is most likely to change management. Joint \202 uid with a white blood cell count >50,000/mm 3 (mainly neutrophils) and a glucose <400 mg/L is highly suggestive of infection. \200 Gonococcus i s the most common cause of monoarthritis in a young, sexually active adult; women during menstruation may be at particular risk. Disseminated go nococcal infection (DGI) may present as a clinical triad of pustular skin lesions, tenosyno vitis, or migratory arthralgias. The cutaneous manifestations are \202 eeting, and are no t required to make this diagnosis. For a nongonococcal septic arthritis, consult orthopedics early to consider arthroscopic washout of knee, hip, or shoulder, and contact microbiology to arrang e a Gram stain of joint \202 uid and set up cultures/ special tests for atypical organism s (especially for a septic arthritis resistant to empiric antibiotics). Table 22.1 Initial choice of antibiotics for septic arthritis based on Gram stain in adults . All antibiotics are given IV initially Gram \200\231 s stain result Probable pathogen Antibiotic choice Nafcillin or Oxacillin (2 g q 4 h) Vancomycin (1 g q 12 h) Vancomycin (1 g q 12 h) Penicill in G (2.5 million U q 4 h) Penicillin G (2.5 million U q 4 h) [or Ampicillin (2g IV q 4 h)] + gentamicin (1 mg/kg q 8 h) Gr am-positive cocci Clusters Staph. aureus (methicillin resistance suspected) Staph. epidermis Streptococci Enterococci Pa irs and chains (urinary, biliary, bowel) Gram-negative cocci (hemorrhagic rash, meningitis) N. gonorrhoeae Ceftriaxone (2 g IV q 24 h) N. meningitides Cefotaxime (2 g IV q 8 h) Gram-negative bacilli Enterobacteriaceae Cipro \202 oxacin (400 mg IV q 12 h) Pseudomonas spp. Cefotaxime (2 g IV q 8 h) Ceftazidime (2 g IV q 8 h) + Gentamicin 5mg/kg IV q 24 h Polymicrobial Clindamycin (600 mg IV q 6 \200\2238 h)+ + cipro \202 oxacin (400 mg IV q 12 h) No organisms seen (healthy young adult) (older adult, under- lying disease) (intravenous dr ug abuser) N. gonorrhoeae Staphylococci Streptococci Enterobacteriaceae Staphylococci Pseudomonas spp. Enterobacteriaceae Ceftriaxone (2 g IV q 24 h) Vancomycin and cefotaxime Vancomycin and ceftazidime S E P T C I A R T H R I T Source: Reprinted with modi \201 cation from Parker, R. H. (1998). Acute bacterial arthrit is. In Orthopedic Infections (ed. D. Schlossberg), p. 74. New York: Springer-Verlag. I S 5 6 3 CHAPTER 22 Rheumatologic emergencies 564 Empiric antibiotic treatment in the absence of a positive Gram stain in adults in a straigh tforward clinical scenario should be IV vancomycin 1 g q 12 h due to the risk of methicilli n-resistant S. aureus (MRSA). For the elderly or immunocompromised patients, a third-genera tion cephalosporin (e.g., ceftriaxone 1 g IV q 12 h or q 24 h) should be added, given the p ossibility of gram-negative infection. Ceftriaxone alone may be reasonable empiric therapy for septic arthritis in areas where MRSA is not a concern. See Table 21.1. IVDU are at particular risk for MRSA. Pseudomonas should be suspected as well, particularly if the patient does not respond to empiric therapy. Speci \201 c management in children (see Figure 22.1) Prompt IV antibiotic therapy is esse ntial. Initially treat according to the most likely organism for the patient \200\231s age: <3 months cover S. aureus , group B strep, and gram negative bacteria; for those 3 months to 2 years cover S. aureus and S. pneumoniae . Older children should be treated for staphyl ococcal and streptococcal infections, as in adults. Postimmediate management of septic arthritis \200 Review analgesia regularly. \200 Rule out multiple foci of infection. \200 Discontinue any immunosuppressants and consider str ess-dose steroids if the patient is systemically unwell and has received chronic steroids. \200 Adjust antibiotics according to culture sensitivities and in discussion with an infectious disease specialist. For affected weight-bearing joints, keep nonweight bearing until there is obvious improveme nt in pain and swelling, and you are con \201 dent the patient is on appropriate antimicro bials. Physical therapists should be involved early to help passive mobilization of joint before patient bears weight. There are little data regarding the optimum duration of antimicrobial therapy; therefore, t he regimen should be individualized. Common protocols include IV antibiotics for 1 \200\223 2 weeks followed by an oral antibiotic for an additional 2 \200\2234 weeks. Reasons for no/poor improvement \200 Consider that you may have the wrong diagnosis: thin k about crystalline arthritis, RA (see Chapter 5), and SpA monoarthritis (see Chapter 8). \200 Consider that the infection has been successfully treated but that the slow progress is due to a superimposed crystal-induced or reactive autoimmune arthritis, foreign body, or background disease (e.g., RA). The antimicrobials may not be covering the infection. Consider multiple infecting organisms (reculture), atypical organisms (e.g., M. marinum, Lyme, fungal). Gonococcal (GC) septic arthritis \200 Cultures can be initially negative. If suspected, r eculture blood but also urethra, cervix (80 \200\22390% positive), rectum, pharynx, pustule s, and joint \202 uid. Send urine for GC nucleic acid detection. SEPTIC ARTHRITIS 565 Use IV ceftriaxone 1 g q 24 h until clinical improvement is observed (as >5% organisms are penicillin resistant) then ce \201 xime 400 mg q 12 h for 1 \200\2232 weeks (or a \202 u oroquinolone, depending on sensitivity testing). \200 Because of increasing resistance, t reatment with cipro \202 oxacin is no longer advisable. Consider empiric therapy for Chlamydia with doxycycline 100 mg daily for 7 days or one dose of azithromycin 1 g, and concurrent testing for HIV and syphilis. All sexual partners should receive one dose of ceftriaxone 250 mg IM and empiric treatment for Chlamydia (preferably azithromycin 1g). Clinical examination reveals painful inflamed joint with restricted range of motion Joint fluid analysis (white blood cell count, chemistries, Gram-stained smear, routine bact erial culture, small amount fluid in blood culture bottle) Initial laboratory evaluation (CBC, ESR, blood culture, plain radiographs, ultrasound if hi ps) - Consult orthopedic specialist Incision and drainage if hips, shoulders Diagnosis not confirmed - Further evaluation for osteomyelitis, exclude other types of non- infectious arthritis - Re-evaluate with respect to antimicrobials Parenteral antimicrobials Confirmed diagnosis (pus +/ or 50 000 WBC +/ or bacteria in joint fluid +/ or pathogen isol ated blood, joint fluid, other) - Continue antimicrobials, adjust based on culture/suscepti bility - Consult pediatric infectious disease specialist Candidates for home therapy* - Motivated family - IV access assured before hospital dischar ge - Home care service has pediatric expertise - Physician overseer designated Good clinical response noted (usually 4 \200\2235 days) - Consider home treatment total dur ation of treatment usuallly 2 \200\2234 weeks Unsatisfactory clinical response Re-evaluation with respect to - Further surgical drainage - Antimicrobial choice, dosage - Other diagnostic studies Clinical and laboratory follow-up weekly Some patients are not candidates for home therapy. The decision may be based on clinical or microbiological features of diseases. There may be situations where therapy cannot be prov ided in a technically satisfactory manner. Fig. 22.1 Management of suspected septic arthritis in the child. Reproduced with the permis sion of Oxford University Press from the Oxford Textbook of Rheumatology 3e , edited by Ise nberg, David et al . CHAPTER 22 Rheumatologic emergencies 566 Infections in patients taking anti-TNF- drugs Background \200 Over the last decade, im munosuppressants that speci \201 cally inhibit the actions of TNF- A have become widely us ed to treat multiple rheumatic diseases. This class of drugs includes in \202 iximab (Remicade ), etanercept (Enbrel ), adali mumab (Humira ), golimumab (Simponi ), and certolizumab (Cimzia ). The risk of infections is increased with anti-TNF- A use; the severity and type of infections associated with anti-TNF- A therapy also needs special consideration . Patients with a history of serious infections should not be treated with this class of dr ug. Patients treated with anti-TNF- A therapy are at particular risk for tuberculosis (TB), histoplasmosis, listeriosis, and other opportunistic infections. Characteristics of infections \200 Patients receiving treatment with anti-TNF- A therapy should be monitored closely for signs of infection, which should be evaluated aggressively. Disseminated fungal and viral infections can occur (see Table 22.2). \200 Re-activation o f latent infections may be a particular problem. \200 Numerous reports of TB occurring wi th anti-TNF- A treatment make the following precautions prudent: \200 Patients with latent TB should be screened prior to initiation of therapy Patients who travel to endemic areas and health care workers should be considered high risk Screening should include intradermal injection of PPD, and consideration of chest radiograph given the possibility of anergy. \200 Induration of (ci d:2) 5 mm should be considered a positive response for most patients with rheumatic disease An interferon- G release assay is also appropriate for screening for latent tuberculosis infection, and is not affected by prior BCG vaccination. Patients with a positive PPD should receive oral isoniazid 300 mg daily with pyridoxine for 9 months (or alternate appropriate regimen) Reactivation of TB should be considered in febrile patients and those not screened for TB before anti-TNF- A treatment. Latent histoplasmosis should be considered in patients from endemic regions or history of potential exposure (e.g., spelunking, construction) The risk and severity of infections may be increased in those also taking other immunosuppressants, especially steroids. Patients may need a longer-than-normal course of antibiotics and need careful re-assessment before restarting anti-TNF- A drugs. INFECTIONS IN PATIENTS TAKING ANTI-TNF-A DRUGS 567 Table 22.2 The range of organisms and type of infections reported in the literature or witn essed by authors in association with anti-TNF- A treatment. Fatalities have occurred Organisms Nature of infection Bacteria M. tuberculosis Disseminated Pulmonary Atypical mycobacteria Listeriosis Septicemia Septic arthritis Meningitis Staphylococcus Septicemia Cavitating pneumonia Salmonella Septicemia Septic arthritis Moraxella Septic arthritis Actinobacillus Septic arthritis Nocardia Viruses Varicella Disseminated H. simplex Severe Hepatitis B Reactivation CMV Disseminated Fungi/ yeasts Candida Septicemia Cryptococcus Pneumonia Aspergillosis Disseminated Sporotrichosis Skin Pneumocystis Disseminated Histoplasmosis Pneumonia Disseminated Pneumonia Disseminated Parasites Leishmaniasis Visceral CHAPTER 22 Rheumatologic emergencies 568 Acute SLE Acute SLE will manifest either as a \202 are in patients with an established di agnosis or as the \201 rst presentation of the disease. Declining C3 and increasing dsDNA titers may predict acute disease \202 ares in some (but not all!) patients. The reader i s referred to Chapter 10 for SLE and Chapter 11 for antiphospholipid syndrome and catastrop hic APS. Diagnosing SLE in an acute medical context \200 Consider SLE as a diagnosis in all young and middle-aged women who present with a history of joint pain, photosensitive rash, or ple uritic chest pain. Raynaud \200\231s phenomenon and recurrent mouth ulcers are non-speci \201 c, but may also appear in association with SLE. As labs usually do not test for ANA, C3/C4, or other serologies urgently, these tests may n ot be available when making an initial diagnosis of SLE. In \202 ammatory markers such as the ESR or CRP may not be a reliable indicator of SLE activity. Acute SLE nephritis (adults) \200 Check the BP accurately, creatinine, blood urea nitroge n, electrolytes, send urine for culture, a spot urine protein/creatinine ratio (as an estim ate of proteinuria) and ultrasound the renal tract to rule out post-renal obstruction. Quanti \201 cation of urinary protein and creatinine grades the severity of the renal lesion and guides the management approach (see Figure 22.2). Control BP. Often a diuretic, ACE inhibitor, or beta blocker are required. Biopsy can inform treatment decisions. Treatment will generally include steroids and oral mycophenolate mofetil (1.0 \200\2231.5 g bid) or IV cyclophospham ide (0.75 g/m 2 IV monthly). Steroid-induced osteoporosis and cardiovascular risk should be managed from the outset. Consider getting the following done early: DEXA scan, ECG, and fas ting lipid panel. Daily calcium (1000 \200\2231500 mg) and vitamin D (800 IU) should be administered to all patients receiving steroids. Patients treated with cyclophosphamide must be counseled about infertility, malignancy, and hemorrhagic cystitis risks, the dose schedules (e.g., MESNA), monitoring (CBC at day 10 af ter and prior to IV pulse to check WBC nadir) and Pneumocystis prophylaxis (e.g., dapsone 1 00 mg po qd-qod) (see Figure 22.2). ACUTE SLE 569 SLE diagnosed Renal involvement Mild/Moderate e.g. proteinuria <1.5 g/day or urine protein/creatinine ratio <50 but normal serum creatinine Severe e.g. proteinuria rising >1.5 g/day or protein/creatinine ratio rising >50 and i seru m creatinine In either case blood pressure control is paramount Corticosteroids start with \211\205 0.5 mg/kg/day plus azathioprine 2 \200\2233 mg/kg/day Corticosteroids start with \211\205 0.5 mg/kg day plus monthly pulses of cyclophosphamide 0.5 \200\2231 g/m2 for 6 months then every 3 months for 2 years or mycophenolate 2 \200\223 3 g/day instead of cyclophosphamide If disease remains active If in spite of treatment the kidneys fail, dialysis and renal transplantation should be con sidered. If still active, options (which are controversial!) include Anti-CD20 Stem cell transplant Fig. 22.2 The management of adult renal SLE: treatment algorithm Reproduced with the permis sion of Oxford University Press from the Oxford Textbook of Rheumatology 3e , edited by Ise nberg, David et al . Acute SLE involving heart and lung (adults) \200 Cardiac and isolated pulmonary manifesta tions of SLE are rare, and in many patients with SLE, acute cardiac and pulmonary features may be due to other common conditions (see Table 22.3). CRP elevation may re \202 ect infection or signi \201 cant pleuropericardial SLE. Lupus pericarditis alone without evidence of cardiac compromise can be treated with NS AIDs and prednisone 20 \200\22340 mg daily for 2 \200\2234 weeks with subsequent steroid ta per. If not due to cardiac failure, acute dyspnea in SLE may be due to intercurrent infection, pneumonitis, pulmonary vasculitis, pulmonary embolism, pulmonary hy pertension, or dyspnea from pleuritic chest pain. Cyclophosphamide should be considered for severe or life-threatening manifestations of SLE. CHAPTER 22 Rheumatologic emergencies 570 Table 22.3 Important aspects in management of acute cardiopulmonary manifestations of SLE i n adults For initial clinical cardiac assessment, consider: ECG, blood for CK, troponin, echocardiogram For initial lung assessment, consider: ABGs, CXR, spirometry, HRCT chest, V/Q scan Pulmonary embolism Especially important to consider in patients who are at high risk (e.g., immobility, recent surgery, nephrotic syndrome). Consider empiric anticoagulation early and check for lupus a nticoagulant, APL antibodies, and complete thrombophilia screen. Pulmonary vasculitis (very rare) Features: severe dyspnea, CT with dependent in \201 ltrates consistent with hemorrhage. Re quires ICU and pulmonary physician support and consideration of plasma exchange. Lupus pneumonitis Requires high-dose steroids (methylprednisolone 1 g IV qd x 3 days followed by prednisone 1 mg/kg/ day) and cyclophosphamide (750 mg/m 2 IV q month, followed by a remission maintenan ce regimen). AZA (up to 2.5 mg per kg/d) may be effective in some cases, although most woul d use cyclophosphamide in these cases. Antiphospholipid syndrome PE associated with APL syndrome in SLE requires lifelong anticoagulation. Speci \201 c therapies Steroids Assuming non-viral infections excluded or treated, most cardiopulmonary SLE manifestations respond to oral prednisone 0.5 \200\2231 mg/d (max 80 mg/d). Consider treatment with methyl prednisolone 1g IV qd x 3 days if the clinical situation is extreme and IV steroids will no t compromise clinical situation. Mycophenolate Mycophenolate mofetil (0.5 mg bid initially increasing after 1 \200\2232 weeks to 1 \200 \2231.5 g bid) is the drug of choice for lupus nephritis, except for patients with rapidly progressive glomerulonephritis, for whom intravenous cyclophosphamide is still indicated. Belimumab Belimumab 10 mg/kg administered intravenously on days 0, 14, 28 and every 28 days afterward s decreases disease activity when added to standard-of-care therapies. Patients with anti-d sDNA antibodies and low serum complements are the most likely to respond. Belimumab should not be used for the treatment of lupus nephritis. Bone protection All patients treated with steroids require daily calcium (1 g) and vitamin D (800 IU). Most should also get bisphosphonate initially, which may be withdrawn if DEXA scan shows good B MD with all T scores > \200\2231.5 ACUTE SLE 571 Acute hematologic manifestations of SLE (adults) \200 Many patients with SLE are Coomb \200\231s positive without having signi \201 cant hemolysis, and do not need to be treated speci \201 cally for this. Features of hemolysis include fever, chills, anemia, elevated bilirubin in serum and urine, low serum haptoglobin and reticulocytosis. \200 Acute thrombocytopenia i s a relatively frequent presentation. \200 If severe, both hemolytic anemia (Hb < 7 mg/dL ) and thrombocytopenia (platelets < 25,000) require high dose prednisone 60 \200\22380 mg/day and intravenous immunoglobulin therapy. Pediatric SLE \200\224acute nephritis \200 The most common lesion is diffuse proliferativ e GN (30 \200\22345% cases). \200 One-third have hypertension, which may need aggressive management. \200 All have microscopic hematuria and proteinuria > 500 mg/24 hours. Howeve r, up to one-third may have a normal serum albumin, and about 50% maintain a normal GFR. Prognosis and therapy of nephritis is guided by the active ISN-grade pathological lesion an d chronicity index; thus biopsy is important. \200 Management includes high dose steroids and cyclophosphamide 750 mg/m 2 IV monthly for 6 \200\22312 months, then quarterly IV cyclophosphamide or mycoph enolate mofetil, especially in older children (see Figure 22.3). In acute fulminant renal disease consider plasmapheresis, although this is not routinely done. Pediatric SLE \200\224acute hematological manifestations \200 Overt hemolysis occurs in < 10%, thrombocytopenia in 15 \200\22345%. \200 Bleeding is uncommon. \200 Most with thro mbocytopenia respond to steroids. IVIG can be used; rituximab may be bene \201 cial in ref ractory cases, although this has not been well studied. A high index of suspicion is needed to diagnose catastrophic APLS. It is characterized by m ultiple organ thromboses and microangiopathic changes. All cases require working closely with hematologists as highly informed interpretation of detailed serial coagulation studies is required. \200 The treatment of hematologic manifestations of SLE is shown in Figure 22.4. 5 7 2 C H A P T E R Diffuse proliferative Focal proliferative with necrotizing lesions Membranous Mesangial focal proliferative Mild or no proliferation Significant proliferation 2 2 R h e u m a t o l o g i c Prednisone 2 mg/kg/day in divided doses (maximum 60 mg/day) Prednisone 1 mg/kg/day (maximum 30 mg) and Prednisone: 1 \200\2232 mg/kg depending upon degree of proliferation (maximum 30 \200\22360 mg/day) Prednisone: 2mg/kg (maximum 60 mg/day) IV Cyclophosphamide (500 \200\2231000 mg/m2) monthly \2276 doses; every 3 months \2274 dose s and every 6 months \2272 doses e m e r g e n c i e s If non-responsive Consider IV Cyclophosphamide (regime as for diffuse proliferative disease) Fig. 22.3 Therapy \202 owchart for treating pediatric SLE nephritis. Reproduced with the permission of Oxford University Press from the Oxford Textbook of Rheum atology 3e , edited by Isenberg, David et al . ACUTE SLE 573 Leucopenia Thrombocytopenia Anemia If unresponsive to treatment of systemic disease Usually marker of disease activity If persistent consider If unresponsive to treatment of systemic disease other causes including drug-induced Prednisone: Prednisone: 1 mg/kg/day 1 \200\2232mg/kg/day (maximum 60 mg) Consider pulse (maximum 30 mg) IV gammaglobulin methylprednislone Consider pulse cyclophosphamide Splenectomy is very controversial Fig. 22.4 Flowchart for treating pediatric hematologic manifestations of SLE. Reproduced with the permission of Oxford University Press from the Oxford Textbook of Rheum atology 3e , edited by Isenberg, David et al . CHAPTER 22 Rheumatologic emergencies 574 Systemic vasculitis A severe vasculitis \202 are should be treated aggressively because p ermanent damage from tissue ischemia may occur rapidly. Patients diagnosed with pulmonary c apillaritis or glomerulonephritis should generally be treated with pulse steroids. The spec i \201 c management of each type of vasculitis is outlined in relevant sections of Chapter 14. Giant cell (temporal) arteritis \200 Because giant cell arteritis (GCA) can lead to crani al ischemic events including blindness and stroke, it is important to treat empirically when suspicion is high . The prevalence of giant cell arteritis increases with age. Visual changes, jaw claudication , and diplopia in the setting of B-type symptoms all support the diagnosis of giant cell ar teritis. Empiric therapy starts with prednisone 1mg/kg/d for 1 month; if the patient presents with visual complaints, it would be prudent to initiate treatment with met hylprednisolone 1 g IV qd for 3 days. Daily aspirin has been associated with a decreased risk of cranial ischemic events, and should be used as part of standard therapy unless there is clear contr aindication. Treatment should not be delayed; biopsy is diagnostically useful up to 2 weeks after steroid therapy is initiated. To optimize yield, temporal artery biopsy should be bilateral, with samples of at least 1.5 cm in length. \200\234Severe \200\235 vasculitis \200 Patients with active vasculitis can quickly deve lop manifestations that threaten life or the function of a vital organ. These patients are sometimes referred to as having \200\234severe \200\235 vasculitis. Severe manifestations of the small vessel vasculitides include pulmonary hemorrhage (or capillaritis) and glomerulonephritis. Severe manifestations of med ium vessel vasculitis include mononeuritis multiplex (i.e., foot drop/wrist drop) or mesent eric angina/ischemia. \200 When glomerulonephritis is suspected, renal biopsy can be very useful to con \201 rm the diagnosis. Severe vasculitis is generally treated with pulse solumedrol 1g IV qd for 3 days, followed by prednisone 1mg/kg/d. Most patients with severe vasculitis will also be treated with oral cyclophosphamide 1.5 \200\2232.0 mg/kg/d. Lower doses should be used in the elderly or in p atients with renal insuf \201 ciency. Cyclophosphamide places patients at risk for Pneumocystis infection, and appropriate chemoprophylaxis should be instituted. Oral cyclophosphamide should be administered in the morning in a single dose to minimize risk of hemorrhagic cystitis. In patients who are at high risk for infection, treatment with intravenous immunoglobulin or plasmapheresis may be appropriate. In patients who continue to decline despite immunosuppression, serious consideration should be given to the possibility that the patient has an infection mimicking a vasculitis \202 are. SCLERODERMA (Scl) CRISES 575 Scleroderma (Scl) crises Renal crisis \200 This may manifest as an acute or subacute hype rtensive crisis, usually within the \201 rst four years after diagnosis of diffuse scleroderma (dcSSc). It can be the presenting feature of SSc (Chapter 12). Glucocorticoids may place a patient with scleroderma at elevated risk of developing scleroderma renal crisis. An abrupt increase in BP >150/85 and new renal insuf \201 ciency are consistent with this diagnosis. Other manifestations include what would be expected with hypertensive emergency, such as microangiopathic hemolytic anemia, encephalopathy, and hype rtensive retinopathy. Acute Scl renal crisis management \200 ACE inhibitors are the cornerstone of management o f renal crisis. The patient should be treated with escalating doses of captopril until bloo d pressure is brought under control. ARB and calcium channel blockers can be added sequenti ally if captopril is inadequate. Fast drops in blood pressure should be avoided, as low perfusion pressures in abnormal rena l vessels may worsen renal failure. Consult nephrology about hemodialysis if necessary. \200 Prompt initial treatment often l eads to re-establishment of good renal function. Pulmonary hypertension \200 Primary pulmonary arterial hypertension (PAH) occurs as a complication of lcSSc, although it can also occur in dcSSc (both as a primary feature and s econdary to pulmonary \201 brosis)