Fever in Systemic Lupus Erythematosus

HPI:

48F with a history of SLE presenting with two weeks of fevers and joint pain. The patient reports progressive development of these symptoms associated with malaise and muscle aches. She also reports two days of cough productive of yellow sputum, but denies chest pain, shortness of breath or hemoptysis. She states that these symptoms are comparable to prior lupus flares but have persisted longer than usual. She has not travelled or been hospitalized recently and has no sick contacts.

PMH:

  • SLE
  • AVN left hip

PSH:

  • Total hip arthroplasty

FH:

Non-contributory

SHx:

  • Denies tobacco, alcohol or drug use.
  • Works as an accountant.
  • No history of TB exposure.

Meds:

  • Methotrexate 50mg p.o. weekly
  • Plaquenil 400mg p.o. daily
  • MVI

Allergies:

NKDA

Physical Exam:

VS: T 39.4 HR 138 RR 19 BP 97/61 O2 98% 2L NC
Gen: Alert, responsive and in no acute distress.
HEENT: PERRL, dry mucous membranes, no oropharyngeal lesions or erythema, TM intact bilaterally, no cervical lymphadenopathy, neck supple.
CV: Tachycardia, regular rhythm without additional heart sounds.
Lungs: Clear to auscultation bilaterally.
Abd: +BS, soft, non-tender, non-distended, no rebound/guarding.
Ext: No peripheral edema, extremities warm and well-perfused, diffuse tenderness to palpation and resisted range of motion of joints with particular involvement of bilateral shoulders, elbows, knees and ankles. No effusion noted, no erythema or warmth.
Neuro: Alert, oriented to self, location and time. PERRL, EOMI, facial sensation intact, facial muscles symmetric, palate rises symmetrically, tongue protrudes midline without fasciculation, peripheral sensation and motor strength grossly intact with normal gait.

Labs/Studies:

  • 0h:
  • CBC: 6.0/7.7/23.5/259
  • BMP: 138/2.8/116/18/12/0.66/71
  • Ca: 5.0 (corrected for hypoalbuminemia: 6.9)
  • Mg: 1.1
  • Lactate: 0.7
  • ESR: 81 (0-20)
  • CRP: 7.99 (0-0.74)
  • C3: 60 (79-152)
  • C4: 13 (16-38)
  • 12h:
  • BMP: 142/4.6/113/26/15/0.75/128
  • Ca: 7.8

Imaging:

  • CXR: Negative for acute cardiopulmonary process.

Assessment/Plan:

48F with a history of SLE presenting with fever and polyarticular arthralgia.

#SIRS: Fever and tachycardia in the setting of immunosuppression. The differential diagnosis includes pneumonia (bacterial, viral, less-likely fungal), which would be community-acquired. Association with polyarticular arthralgia suggests symptoms may represent lupus flare given no leukocytosis and elevated CRP.

#Hypocalcemia: Asymptomatic, likely due to hypoalbuminemia and hypomagnesemia. Improved after IV fluids and correction of hypokalemia, hypomagnesemia.

Hospital Course:

The patient was admitted and completed a 7-day course of ceftriaxone and azithromycin. Rheumatology was consulted for management of lupus flare, which included resuming home medications and a prednisone taper upon discharge.
The patient was admitted ten days later, presenting with fevers, productive cough and pleuritic chest pain. Found to have a left lower lobe sub-segmental pulmonary embolus and antiphospholipid syndrome. She was also treated empirically for healthcare-associated pneumonia with cefepime and vancomycin given fever and productive cough though there were no imaging findings suggestive of consolidation and sputum cultures were negative.

Differential Diagnosis of Hypocalcemia: 1,2

Differential Diagnosis of Hypocalcemia

Laboratory Evaluation of Hypocalcemia: 1,2

Laboratory Evaluation of Hypocalcemia

Clinical Manifestations of Hypocalcemia: 1

  • Neuromuscular
    • Hyperexcitability
    • Perioral paresthesias
    • Muscle weakness, cramps, fasciulations, tetany
  • CNS
    • Depression
    • Irritability
    • Confusion
    • Seizure
  • Cardiac
    • Decreased contractility/conduction
    • QT prolongation

Management of Symptomatic Hypocalcemia: 1

  • 10mL 10% Calcium Gluconate
  • Dilute in 100mL D5W

Fever in SLE:

It is important to differentiate whether fever in a patient with SLE is due to disease activity (flare) or active infection.

Risk Factors for Infection:3

  • Neutropenia/Lymphopenia
  • Hypocomplementemia
  • Immunosuppressive therapy (especially Azathioprine4)

Laboratory Studies:3

  • CRP: sensitivity 100%, specificity 90% >1.35mg/dL 5
  • PCT: sensitivity 75%, specificity 75% 6

References:

  1. Cooper, M. S., & Gittoes, N. J. L. (2008). Diagnosis and management of hypocalcaemia. BMJ (Clinical research ed.), 336(7656), 1298–1302. doi:10.1136/bmj.39582.589433.BE
  2. Hannan, F. M., & Thakker, R. V. (2013). Investigating hypocalcaemia. BMJ (Clinical research ed.), 346(may09 1), f2213–f2213. doi:10.1136/bmj.f2213
  3. Cuchacovich, R., & Gedalia, A. (2009). Pathophysiology and clinical spectrum of infections in systemic lupus erythematosus. Rheumatic diseases clinics of North America, 35(1), 75–93. doi:10.1016/j.rdc.2009.03.003
  4. Zhou, W. J., & Yang, C.-D. (2009). The causes and clinical significance of fever in systemic lupus erythematosus: a retrospective study of 487 hospitalised patients. Lupus, 18(9), 807–812. doi:10.1177/0961203309103870
  5. Kim, H.-A., Jeon, J.-Y., An, J.-M., Koh, B.-R., & Suh, C.-H. (2012). C-reactive protein is a more sensitive and specific marker for diagnosing bacterial infections in systemic lupus erythematosus compared to S100A8/A9 and procalcitonin. The Journal of rheumatology, 39(4), 728–734. doi:10.3899/jrheum.111044
  6. Scirè, C. A., Cavagna, L., Perotti, C., Bruschi, E., Caporali, R., & Montecucco, C. (2006). Diagnostic value of procalcitonin measurement in febrile patients with systemic autoimmune diseases. Clinical and experimental rheumatology, 24(2), 123–128.

Cervical Lymphadenopathy

32 year-old male, previously healthy, with slowly-progressive right and left cervical lymphadenopathy over the past three years. He first noted the development of a mass on the lateral neck below the ear three years ago. This mass was non-tender and remained stable at approximately the size of a marble for nearly one year. He later developed more and larger masses, but never experienced any constitutional symptoms like fevers, night sweats, fatigue or weight loss. Examination reveals a healthy, well-nourished male with multiple, hard, mobile, non-tender right posterior cervical and submandibular lymph nodes and a large left supraclavicular lymph node, protruding above the clavicle and measuring ~4x3cm.

Imaging:

Cervical Lymphadenopathy - Axial

Cervical Lymphadenopathy - Axial

- Left supra-clavicular lymph node, 4.5 x 2.9 cm
- Right posterior submandibular lymph node, 3.5 x 2.7 cm
- Multiple other small cervical lymph nodes, more on the right

Cervical Lymphadenopathy - Coronal

Cervical Lymphadenopathy - Coronal

- Left supra-clavicular lymph node, 4.5 x 2.9 cm
- Right posterior submandibular lymph node, 3.5 x 2.7 cm
- Multiple other small cervical lymph nodes, more on the right

He has undergone several diagnostic procedures during this time including aspirations and core biopsies with inconclusive pathology and he is currently admitted for an excisional biopsy of the supraclavicular lymph node. Infectious and rheumatologic workup has remained negative including: HIV, bartonella, Quantiferon TB Gold, cocci, histo, toxo, CMV, EBV, ANA, RF, ACE.

The patient tolerated the excisional biopsy without complication and was discharged. Preliminary pathology suggests Castleman’s disease.

Lymph nodes and their drainage: 1,2

Lymph Nodes of the Body
Lymph Nodes of the Head and Neck

Evaluation of Lymphadenopathy: 2,3,4

Evaluation of Lymphadenopathy

References:

  1. Ferrer R. Lymphadenopathy: differential diagnosis and evaluation. Am Fam Physician. 1998;58(6):1313–1320.
  2. Henry PH, Longo DL. Chapter 59. Enlargement of Lymph Nodes and Spleen. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 18e. New York: McGraw-Hill; 2012.
  3. Armitage JO. Chapter 171. Approach to the Patient With Lymphadenopathy and Splenomegaly In: Cecil, Russell L., Lee Goldman, and Andrew I. Schafer. Goldman’s Cecil medicine. Philadelphia: Elsevier/Saunders, 2011.
  4. Motyckova G, Steensma DP. Why does my patient have lymphadenopathy or splenomegaly? Hematol. Oncol. Clin. North Am. 2012;26(2):395–408– ix. doi:10.1016/j.hoc.2012.02.005.

Joint Pain and Tremor

HPI:

47 year-old female with a history of arthritis, gout and AVP (5/2013) resulting in tib/fib fracture s/p ORIF presenting with severe joint pain, worsening in the past week such that she has been unable to walk. While she reported significant diffuse joint pain, it was predominantly focused on her left leg, bilateral knees, and left shoulder. Joint pain progressively worsens over the course of the day and is worse with activity (better at rest). She reported occasional joint swelling, but no redness, fevers/chills, new trauma, recent travel, and is not sexually active. She reports suffering from joint pain for over 10 years, previously well-controlled with OTC pain medications (ibuprofen), however this had grown ineffective in the past week. She had been prescribed Norco after her surgery but was unable to afford it. She denies any recent intake of foods that have previously been triggers for acute gouty flares.

PMH:

  • Arthritis
  • Gout

PSH:

  • Left tib/fib fracture s/p ORIF

FH:

  • No family history of RA, SLE or joint disease.

SHx:

  • No t/e/d use
  • Lives at home alone

Meds:

  • Ibuprofen 800mg p.o. p.r.n. pain

Allergies:

NKDA

Physical Exam:

VS: T 98.1 HR 109 RR 18 BP 108/66 O2 95% RA
Gen: Thin female, appearing older than her stated age, in significant pain when helped to transfer to bed for examination
HEENT: PERRL, MMM, no lesions
CV: RRR, normal S1/S2, no M/R/G
Lungs: CTAB, no crackles/wheezing
Abd: +BS, soft, NT/ND, no masses
Ext: Knees appear symmetric, no deformities, no erythema or warmth to touch, no effusion detected, significant tenderness to light touch of bilateral knees. Significant decreased ROM 2/2 pain in b/l lower extremities, limited to 30 degrees of knee flexion, unable to test strength 2/2 pain.Left lower extremity with 6cm longitudinal incisions on lateral and medial aspects of leg. Incisions appear well-healed without erythema/discharge. Decreased sensation on lateral and medial aspects of left leg.

Left shoulder appears normal, no obvious deformities, no bony tenderness. Decreased ROM to 15 degrees of abduction/flexion/extension 2/2 pain.

Neuro: AAOx4, CN II-XII intact, gait not tested. A high-frequency, high-amplitude tremor is noted in the bilateral upper extremities at rest and with activity. Tremor appears associated with patient’s distress and pain.

Labs/Studies:

  • CBC: 9.4/12.8/38.1/311
  • BMP: 135/3.9/100/27/14/0.60/113
  • CRP: 0.18
  • ESRW: 20
  • Uric Acid: 2.6
  • XR Left Tibia/Fibula: There is a metallic fixation device noted in the tibia.  There is no evidence of loosening of the metallic components.  The bones appear to be in gross anatomic alignment.

Assessment/Plan:

47F w/hx arthritis, gout, recent tib/fib fx s/p ORIF presenting with worsening polyarticular arthralgia unresponsive to OTC medications admitted for evaluation and pain management.

# Polyarticular arthralgia: Multiple joints affected, however patient notes most significant in bilateral knees and recently operated left leg. Polyarticular involvement, symmetric distribution and predominant involvement of large joints is suggestive of osteoarthritis. Also, given patient’s significant distress and multiple points of tenderness, potential extra-articular cause such as complex regional pain syndrome. Unlikely inflammatory arthritis (infectious, crystal arthropathy, rheumatic disease) given distribution and no significant erythema, warmth or effusion which could be aspirated. Obtained imaging of LLE to evaluate recent surgical repair of tib/fib fracture, with no evidence of loosening of fixation components or misalignment. Patient’s symptoms improved with morphine 5mg i.v. x2 in ED. Will admit for continued evaluation and pain management, consider addition of gabapentin for potential neuropathic pain associated with recent surgery.

# Tremor: High-frequency, high-amplitude rest and action tremor suggestive of essential tremor or exaggerated physiological tremor associated with pain and emotional distress. No other neurological symptoms (HA, weakness) and non-focal neurological exam (aside from anesthesia localized around recent surgical incisions in LLE). Will continue monitoring, no need for imaging at this time.

# Gout: Patient with history of gout, however, doubt that current arthralgia associated with acute gouty flare. Will continue monitoring exam and consider ortho consultation for joint aspiration.

Differential Diagnosis of Monoarticular Arthralgia: 1,2

Differential Diagnosis of Monoarticular Arthralgia

Differential Diagnosis of Polyarticular Arthralgia 1,3

Differential Diagnosis of Polyarticular Arthralgia

Use of Serum Uric Acid in Acute Gout 4

In this patient, serum uric acid levels were checked. However, a normal serum urate (SU) does not exclude an acute gout flare. Studies have shown 12-43% of patients with acute gout flares have normal SU. An elevated SU (>8.0mg/dL) may support the diagnosis of a gout flare but is not itself diagnostic.

Approach to Joint Pain: 3

Approach to Joint Pain

Certain key historical elements can help narrow the differential diagnosis.

  1. Inflammation:
    1. Definition: Presence of erythema, warmth, swelling, pain with passive ROM, morning stiffness suggests inflammatory cause (arthritis)
    2. Common causes: Infection, gout, RA, SLE
  2. Chronology:
    1. Definition: Acute <6wks, chronic > 6wks
  3. Distribution:
    1. Definition: Location (large/small), symmetry
    2. Common causes:
      1. OA: DIP + PIP, spares wrists, elbows, ankles
      2. RA: PIP + MCP
      3. Spondylarthropathies (large joints)
      4. Symmetric involvement: RA, SLE
      5. Asymmetric involvement: Psoriatic arthritis, reactive arthritis, gout
  4. Course:
    1. Definition: Intermittent (gout), migrating (GC, Lyme, SLE)
  5. Demographics:
    1. Female <50: RA, SLE
    2. Male > 40: gout (♂ 20yr after puberty, ♀ 20yr after menopause)
  6. Extra-articular manifestations:
    1. Malar rash, oral ulcers: SLE
    2. Proximal muscle weakness: polymyositis
    3. Psoriatic skin/nail lesions: psoriatic arthritis
    4. Oral ulcers, vesicopustules on palms/soles, recent diarrheal illness: reactive arthritis

Differential Diagnosis of Tremor: 5,6

Differential Diagnosis of Joint Pain

References:

  1. Cush JJ, Lipsky PE. Chapter 331. Approach to Articular and Musculoskeletal Disorders. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012. http://www.accessmedicine.com/content.aspx?aID=9139045. Accessed August 27, 2013.
  2. Siva, C., Velazquez, C., Mody, A., & Brasington, R. (2003). Diagnosing acute monoarthritis in adults: a practical approach for the family physician. American family physician, 68(1), 83–90.
  3. Mies Richie, A., & Francis, M. L. (2003). Diagnostic approach to polyarticular joint pain. American family physician, 68(6), 1151–1160.
  4. Schlesinger, N., Norquist, J. M., & Watson, D. J. (2009). Serum urate during acute gout. The Journal of rheumatology, 36(6), 1287–1289. doi:10.3899/jrheum.080938
  5. Hess, C. W., & Pullman, S. L. (2012). Tremor: clinical phenomenology and assessment techniques. Tremor and other hyperkinetic movements (New York, N.Y.).
  6. Crawford, P., & Zimmerman, E. E. (2011). Differentiation and diagnosis of tremor. American family physician, 83(6), 697–702.