574083
research-article2015
CPJXXX10.1177/0009922815574083Clinical PediatricsLevkowitz et al
Resident Rounds
Severe Musculoskeletal Pain in a Patient With Systemic Lupus Erythematosus
Clinical Pediatrics 1–3 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0009922815574083 cpj.sagepub.com
Eilan Levkowitz, MD1,2, Amanda G. Brown, MD1,2, and Abraham Gedalia, MD1,2 Case Report A 17-year-old African American female presented to our emergency room with a red, round, raised papular rash and a severe bilateral pain and swelling of the knees, ankles, wrists, and small joints of her hands. She was unable to bend her knees or walk due to intense localized knee pain that she noted to be “more painful than usual,” with tenderness to the touch and unresponsive to home nonsteriodal anti-inflammatory drugs and opiates. She also complained of fevers with spikes around 102°F and spreading of the rash to her face. The patient’s joint swelling originated in right ankle, and later to the other joints. Additional treatment with naproxen provided no relief of symptoms. She denied any nausea, vomiting, diarrhea, abdominal pain, or difficulty breathing. She also denied any previous sexual activity. Two weeks prior to admission, she was diagnosed with systemic lupus erythematosus (SLE) at the rheumatology clinic. At that time, an ANA profile showed positive ANA, and the double-stranded DNA, RNP, SSA, and SSB antibodies were positive, but SM, Scl-70, and anti-centromere antibodies were negative. Her white blood cell count was 8000/mm3 with normal differential, and C-reactive protein (CRP) was slightly elevated at 3 mg/dL (normal 0-0.5 mg/dL). Her hemoglobin and hematocrit were 10.6 g/dL and 31.9%, respectively (normal 12-14 g/dL and 36% to 41%, respectively), complement components C3 and C4 levels were decreased at 35.4 and 5.0 mg/dL (normal 83-177 and 15-45 mg/dL, respectively), and IgG level was elevated at 2230 mg/dL (normal 5951275 mg/dL). On diagnosis of SLE, she was placed on oral prednisone of 20 mg twice a day and hydroxychloroquine 300 mg daily. She had no known drug allergies. Her family history was significant for a grandmother with rheumatoid arthritis. On examination, the patient was awake and alert but experiencing severe pain. She had significant joint swelling, redness, and tenderness to palpation of knees, ankles, elbows, wrists, with evidence of tenosynovitis in both hands. In addition, she also had nonblanching pink
patches and plaques ranging from 1 to 3 mm on her palms, wrists, arms, and face. Laboratory testing showed an elevated white blood cell count of 14 290/mm3 (normal 4500-13 000/mm3) with 89% segmented neutrophils found in the differential, and a significantly elevated CRP of 17.5 mg/dL, and normal platelets of 182 000/mm3 (normal 150 000350 000/mm3). The patient’s hemoglobin and hematocrit were reduced to 10.3 g/dL and 24.9%, respectively. Blood culture showed no growth. Urinalysis showed 1+ protein, 25 to 35 white blood cells, 15 to 25 red blood cells with trace leukocyte esterase and negative bacteria. Complete metabolic panel was within normal limits. Her complement components C3 and C4 were both slightly decreased at 78 mg/dL and 16.1 mg/dL, respectively. Quantitative immunoglobulin IgG was elevated at 1890 mg/dL. The IgA and IgM were both within normal limits. The working diagnosis was SLE with significant flare in the joints, and she was started on intravenous methylprednisolone, oral hydroxychloroquine, and cyclobenzaprine and meloxicam. Because of the fever, rash, tenosynovitis, and unresponsive severe pain, a possible diagnosis of gonococcal infection was considered in addition to her underlying diagnosis of SLE. Her right knee was aspirated and the culture showed moderate growth of Neisseria gonorrhoeae. Based on these findings, she was diagnosed with disseminated gonococcal infection and treated with ceftriaxone (1 g intravenous) and 7-day oral course of cefixime (400 mg twice a day) and doxycycline (100 mg daily) and she was seen in follow-up in 3 weeks and there was no evidence of arthritis, morning stiffness, muscle pain, fevers, or rash. 1
LSU Health Sciences Center, New Orleans, LA, USA Children’s Hospital, New Orleans, LA, USA
2
Corresponding Author: Abraham Gedalia, Children’s Hospital, 200 Henry Clay Avenue, New Orleans, LA 70118, USA. Email: [email protected]
Downloaded from cpj.sagepub.com at UCSF LIBRARY & CKM on March 12, 2015
2
Clinical Pediatrics
Final Diagnosis Disseminated gonococcal infection (DGI) with systemic lupus erythematosus (SLE).
Discussion Disseminated gonococcal infection (DGI) and a flare of SLE have overlapping dermatitis and arthritis symptoms that can be difficult to differentiate. The classic suppurative arthritis syndrome presentation of DGI with a single hot, swollen, joint is only present in 20% to 30% of patients. The tenosynovitis-dermatitis syndrome involving polyarthritis/arthralgias and skin lesions that resemble an SLE flare are present in approximately 50% of initial manifestations.1 Our patient probably had clinical manifestations of both the above DGI variants. Neisseria gonorrhoeae is a highly transmissible, sexually transmitted infection that causes an estimated 820 000 new infections per year in the United States,2 less than half of which are detected and reported. DGI occurs in 1% to 3% of all gonococcal infections.3 The majority of infections occur in sexually active teens and young adults aged 15 through 24 years, with the rate of infection higher in females than in males (and 17 times more common in black females than in white females).4 The infection can also spread vertically from mother to neonate during childbirth. Potential manifestations range from mild to severe symptoms affecting the pharynx, urethra, anus, endocervix, and epididymis. Early infections can be asymptomatic in all populations, allowing the infection in 10% to 20% of untreated women to spread into the uterus and fallopian tubes causing silent to life-threatening manifestations of pelvic inflammatory disease; nearly 20% of these women experience subsequent uterine tubal scarring, increasing the risk of ectopic pregnancy, tubo-ovarian abscess, and involuntary infertility. As the infection disseminates, it can cause petechial or pustular dermatitis, asymmetrical arthlargia, osteomyelitis, meningitis, septic arthritis, tenosynovitis, perihepatitis known as Fitz-Hugh-Curtis syndrome, and septic shock.3 The original diagnosis of SLE in our patient was supported by her clinical manifestations, the hypocomplementemia, and positive anti–double-stranded DNA antibodies. Patients with SLE carry an increased risk for severe gonorrheal infection because of the nature and management of the disease. Reasons include an iatrogenic induced immunosuppressive state from being on immunosuppressive agents, inherited or acquired complement deficiencies5 that occur secondary to increased
C3 and C4 consumption during an SLE flare,6 delayed recognition, and the impairment of the disposal of immune complexes and bacteriolysis by the mononuclear phagocytic system.7 C-reactive protein is a poor marker for a SLE flare; however, an elevated CRP warrants a search for a coinciding inflammation or infection.8 As evident in our case, the CRP was only mildly elevated during her initial presentation of SLE, and was significantly elevated during the DGI. The character and increased intensity of our patient’s tenosynovitis, monoarticular severe pain that was unresponsive to steroids, nonsteroidal antiinflammatory drugs, or opiates hinted that her symptoms may not solely be the result of SLE flare. Specific testing for diagnosis includes culture, nucleic acid hybridization test, and nucleic acid amplification tests on urine and other body fluid samples. In suppurative arthritis syndrome, synovial fluid cultures are positive in 45% to 55%, while blood cultures are generally negative. In tenosynovitis-dermatitis syndrome, 30% to 40%, blood cultures are positive, while synovial cultures are generally negative.3 Recommended therapy for DGI is ceftriaxone or cefotaxime for a 7 day total course. Chlamydia trachomatis should be presumptively treated.9 Author Contributions EL is a pediatric resident that managed with us this patient and with our direction wrote the case report. AGB and AG are the rheumatology attendings incharge of the management and helped to put together the discussion.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Dallabetta G, Hook EW 3rd. Gonococcal infections. Infect Dis Clin North Am. 1987:1:25-54. 2. Centers for Disease Control and Prevention. Gonorrhea— CDC fact sheet. 2014. http://www.cdc.gov/std/gonorrhea/ stdfact-gonorrhea.htm. Accessed September 13, 2014. 3. Darville T. Neisseria gonorrhoeae (gonococcus). In: Kliegman RM, Stanton BF, St Geme JW 3rd, Schor NF, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Saunders Elsevier; 2011:935-938.
Downloaded from cpj.sagepub.com at UCSF LIBRARY & CKM on March 12, 2015
3
Levkowitz et al 4. Walker CK, Sweet RL. Gonorrhea infection in women: prevalence, effects, screening, and management. Int J Womens Health. 2011;3:197-206. 5. Ellison RT 3rd, Curd JG, Kohler PF, Reller LB, Judson FN. Underlying complement deficiency in patients with disseminated gonococcal infection. Sex Transm Dis. 1987;14:201-204. 6. Cooper MA, White AJ. Systemic lupus erythematosus. In: Dusenbery SM, White AJ, eds. The Washington Manual of Pediatrics. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins; 2009:379-380.
7. Walport MJ. Complement deficiency and disease. Br J Rheumatol. 1993;33:269-273. 8. Rezaieyazdi Z, Sahebari M, Hatef M, et al. Is there any correlation between high sensitive CRP and disease activity in systemic lupus erythematosus? Lupus. 2011;20: 1494-1500. 9. American Academy of Pediatrics. Gonococcal infections. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book. 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:305-312.
Downloaded from cpj.sagepub.com at UCSF LIBRARY & CKM on March 12, 2015
research-article2015
CPJXXX10.1177/0009922815574083Clinical PediatricsLevkowitz et al
Resident Rounds
Severe Musculoskeletal Pain in a Patient With Systemic Lupus Erythematosus
Clinical Pediatrics 1–3 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0009922815574083 cpj.sagepub.com
Eilan Levkowitz, MD1,2, Amanda G. Brown, MD1,2, and Abraham Gedalia, MD1,2 Case Report A 17-year-old African American female presented to our emergency room with a red, round, raised papular rash and a severe bilateral pain and swelling of the knees, ankles, wrists, and small joints of her hands. She was unable to bend her knees or walk due to intense localized knee pain that she noted to be “more painful than usual,” with tenderness to the touch and unresponsive to home nonsteriodal anti-inflammatory drugs and opiates. She also complained of fevers with spikes around 102°F and spreading of the rash to her face. The patient’s joint swelling originated in right ankle, and later to the other joints. Additional treatment with naproxen provided no relief of symptoms. She denied any nausea, vomiting, diarrhea, abdominal pain, or difficulty breathing. She also denied any previous sexual activity. Two weeks prior to admission, she was diagnosed with systemic lupus erythematosus (SLE) at the rheumatology clinic. At that time, an ANA profile showed positive ANA, and the double-stranded DNA, RNP, SSA, and SSB antibodies were positive, but SM, Scl-70, and anti-centromere antibodies were negative. Her white blood cell count was 8000/mm3 with normal differential, and C-reactive protein (CRP) was slightly elevated at 3 mg/dL (normal 0-0.5 mg/dL). Her hemoglobin and hematocrit were 10.6 g/dL and 31.9%, respectively (normal 12-14 g/dL and 36% to 41%, respectively), complement components C3 and C4 levels were decreased at 35.4 and 5.0 mg/dL (normal 83-177 and 15-45 mg/dL, respectively), and IgG level was elevated at 2230 mg/dL (normal 5951275 mg/dL). On diagnosis of SLE, she was placed on oral prednisone of 20 mg twice a day and hydroxychloroquine 300 mg daily. She had no known drug allergies. Her family history was significant for a grandmother with rheumatoid arthritis. On examination, the patient was awake and alert but experiencing severe pain. She had significant joint swelling, redness, and tenderness to palpation of knees, ankles, elbows, wrists, with evidence of tenosynovitis in both hands. In addition, she also had nonblanching pink
patches and plaques ranging from 1 to 3 mm on her palms, wrists, arms, and face. Laboratory testing showed an elevated white blood cell count of 14 290/mm3 (normal 4500-13 000/mm3) with 89% segmented neutrophils found in the differential, and a significantly elevated CRP of 17.5 mg/dL, and normal platelets of 182 000/mm3 (normal 150 000350 000/mm3). The patient’s hemoglobin and hematocrit were reduced to 10.3 g/dL and 24.9%, respectively. Blood culture showed no growth. Urinalysis showed 1+ protein, 25 to 35 white blood cells, 15 to 25 red blood cells with trace leukocyte esterase and negative bacteria. Complete metabolic panel was within normal limits. Her complement components C3 and C4 were both slightly decreased at 78 mg/dL and 16.1 mg/dL, respectively. Quantitative immunoglobulin IgG was elevated at 1890 mg/dL. The IgA and IgM were both within normal limits. The working diagnosis was SLE with significant flare in the joints, and she was started on intravenous methylprednisolone, oral hydroxychloroquine, and cyclobenzaprine and meloxicam. Because of the fever, rash, tenosynovitis, and unresponsive severe pain, a possible diagnosis of gonococcal infection was considered in addition to her underlying diagnosis of SLE. Her right knee was aspirated and the culture showed moderate growth of Neisseria gonorrhoeae. Based on these findings, she was diagnosed with disseminated gonococcal infection and treated with ceftriaxone (1 g intravenous) and 7-day oral course of cefixime (400 mg twice a day) and doxycycline (100 mg daily) and she was seen in follow-up in 3 weeks and there was no evidence of arthritis, morning stiffness, muscle pain, fevers, or rash. 1
LSU Health Sciences Center, New Orleans, LA, USA Children’s Hospital, New Orleans, LA, USA
2
Corresponding Author: Abraham Gedalia, Children’s Hospital, 200 Henry Clay Avenue, New Orleans, LA 70118, USA. Email: [email protected]
Downloaded from cpj.sagepub.com at UCSF LIBRARY & CKM on March 12, 2015
2
Clinical Pediatrics
Final Diagnosis Disseminated gonococcal infection (DGI) with systemic lupus erythematosus (SLE).
Discussion Disseminated gonococcal infection (DGI) and a flare of SLE have overlapping dermatitis and arthritis symptoms that can be difficult to differentiate. The classic suppurative arthritis syndrome presentation of DGI with a single hot, swollen, joint is only present in 20% to 30% of patients. The tenosynovitis-dermatitis syndrome involving polyarthritis/arthralgias and skin lesions that resemble an SLE flare are present in approximately 50% of initial manifestations.1 Our patient probably had clinical manifestations of both the above DGI variants. Neisseria gonorrhoeae is a highly transmissible, sexually transmitted infection that causes an estimated 820 000 new infections per year in the United States,2 less than half of which are detected and reported. DGI occurs in 1% to 3% of all gonococcal infections.3 The majority of infections occur in sexually active teens and young adults aged 15 through 24 years, with the rate of infection higher in females than in males (and 17 times more common in black females than in white females).4 The infection can also spread vertically from mother to neonate during childbirth. Potential manifestations range from mild to severe symptoms affecting the pharynx, urethra, anus, endocervix, and epididymis. Early infections can be asymptomatic in all populations, allowing the infection in 10% to 20% of untreated women to spread into the uterus and fallopian tubes causing silent to life-threatening manifestations of pelvic inflammatory disease; nearly 20% of these women experience subsequent uterine tubal scarring, increasing the risk of ectopic pregnancy, tubo-ovarian abscess, and involuntary infertility. As the infection disseminates, it can cause petechial or pustular dermatitis, asymmetrical arthlargia, osteomyelitis, meningitis, septic arthritis, tenosynovitis, perihepatitis known as Fitz-Hugh-Curtis syndrome, and septic shock.3 The original diagnosis of SLE in our patient was supported by her clinical manifestations, the hypocomplementemia, and positive anti–double-stranded DNA antibodies. Patients with SLE carry an increased risk for severe gonorrheal infection because of the nature and management of the disease. Reasons include an iatrogenic induced immunosuppressive state from being on immunosuppressive agents, inherited or acquired complement deficiencies5 that occur secondary to increased
C3 and C4 consumption during an SLE flare,6 delayed recognition, and the impairment of the disposal of immune complexes and bacteriolysis by the mononuclear phagocytic system.7 C-reactive protein is a poor marker for a SLE flare; however, an elevated CRP warrants a search for a coinciding inflammation or infection.8 As evident in our case, the CRP was only mildly elevated during her initial presentation of SLE, and was significantly elevated during the DGI. The character and increased intensity of our patient’s tenosynovitis, monoarticular severe pain that was unresponsive to steroids, nonsteroidal antiinflammatory drugs, or opiates hinted that her symptoms may not solely be the result of SLE flare. Specific testing for diagnosis includes culture, nucleic acid hybridization test, and nucleic acid amplification tests on urine and other body fluid samples. In suppurative arthritis syndrome, synovial fluid cultures are positive in 45% to 55%, while blood cultures are generally negative. In tenosynovitis-dermatitis syndrome, 30% to 40%, blood cultures are positive, while synovial cultures are generally negative.3 Recommended therapy for DGI is ceftriaxone or cefotaxime for a 7 day total course. Chlamydia trachomatis should be presumptively treated.9 Author Contributions EL is a pediatric resident that managed with us this patient and with our direction wrote the case report. AGB and AG are the rheumatology attendings incharge of the management and helped to put together the discussion.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Dallabetta G, Hook EW 3rd. Gonococcal infections. Infect Dis Clin North Am. 1987:1:25-54. 2. Centers for Disease Control and Prevention. Gonorrhea— CDC fact sheet. 2014. http://www.cdc.gov/std/gonorrhea/ stdfact-gonorrhea.htm. Accessed September 13, 2014. 3. Darville T. Neisseria gonorrhoeae (gonococcus). In: Kliegman RM, Stanton BF, St Geme JW 3rd, Schor NF, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Saunders Elsevier; 2011:935-938.
Downloaded from cpj.sagepub.com at UCSF LIBRARY & CKM on March 12, 2015
3
Levkowitz et al 4. Walker CK, Sweet RL. Gonorrhea infection in women: prevalence, effects, screening, and management. Int J Womens Health. 2011;3:197-206. 5. Ellison RT 3rd, Curd JG, Kohler PF, Reller LB, Judson FN. Underlying complement deficiency in patients with disseminated gonococcal infection. Sex Transm Dis. 1987;14:201-204. 6. Cooper MA, White AJ. Systemic lupus erythematosus. In: Dusenbery SM, White AJ, eds. The Washington Manual of Pediatrics. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins; 2009:379-380.
7. Walport MJ. Complement deficiency and disease. Br J Rheumatol. 1993;33:269-273. 8. Rezaieyazdi Z, Sahebari M, Hatef M, et al. Is there any correlation between high sensitive CRP and disease activity in systemic lupus erythematosus? Lupus. 2011;20: 1494-1500. 9. American Academy of Pediatrics. Gonococcal infections. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book. 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:305-312.
Downloaded from cpj.sagepub.com at UCSF LIBRARY & CKM on March 12, 2015
