Case 11-2004: A Boy with Rash, Edema, and Hypertension
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《新英格兰医药杂志》
To the Editor: In the discussion of Case 11-2004, which involved a young boy with systemic lupus erythematosus, Dr. Somers and colleagues (April 8 issue)1 state that "a definitive diagnosis of systemic lupus erythematosus requires that 4 of 11 criteria be met over time." This statement unfortunately perpetuates a common misconception. The American College of Rheumatology criteria for the classification of rheumatic diseases, including the criteria for the classification of systemic lupus erythematosus,2,3 are empirical and not intended to include or exclude a particular diagnosis in any individual patient. The main intent of establishing these criteria was to offer a standard that permits comparisons of groups of patients from different centers that take part in various clinical investigations, including therapeutic trials.
Rajiv K. Dixit, M.D.
Northern California Arthritis Center
Walnut Creek, CA 94598
References
Case Records of the Massachusetts General Hospital (Case 11-2004). N Engl J Med 2004;350:1550-1559.
Tan EM, Cohen A, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271-1277.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725-1725.
To the Editor: In Case 11-2004, the absence of eosinophiluria and lack of improvement on discontinuation of amoxicillin were cited in ruling out drug-induced nephritis. However, allergic interstitial nephritis is characterized by tubulointerstitial infiltration with granulocytes and typically, but not invariably, eosinophils.1 Furthermore, eosinophiluria is neither sensitive nor specific, and eosinophilia is seen only in one third of cases of acute interstitial nephritis.2 It generally takes about four to six weeks for the symptoms to resolve after discontinuation of drugs,3 and with renal failure, the half-life of amoxicillin increases by a factor of seven, leading to its retention.4 The temporal correlation of rash and renal failure after amoxicillin use, the absence of hematologic derangements (which are common in children with systemic lupus erythematosus but were not seen in this case), and specific tests for systemic lupus (e.g., a test for anti–double-stranded DNA antibodies) point more toward type III hypersensitivity, in my view.
The statement that labetalol is a selective beta-blocker is incorrect. It has alpha-blocking as well as beta-blocking properties, though its clinical effect is similar to that of a selective beta-blocker.4
G. Sivagnanam, M.D.
Chengalpattu Medical College
Chengalpattu 603 001, India
drsivagnanam@rediffmail.com
References
Brady HR, Brenner BM. Acute renal failure. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison's principles of internal medicine. 15th ed. Vol. 2. New York: McGraw Hill, 2001:1541-51.
Kher V, Arora P. Acute interstitial nephritis. In: Mandal AK, ed. Text book of nephrology for the Asian-Pacific physicians. 2nd ed. New Delhi, India: Jaypee Brothers, 2004:123-32.
Mathew C, Joshi VR. Systemic lupus erythematosus. In: Sen Gupta PC, ed. Clinical immunology. New Delhi, India: Oxford University Press, 2003:667-80.
Arterial hypertension, angina pectoris, myocardial infarction and kidney and urinary tract. In: Lawrence DR, Bennet PN, Brown MJ. Clinical pharmacology. 8th ed. Edinburgh: Churchill Livingstone, 1997:443, 484-99.
The authors reply: The clinical manifestations of systemic lupus erythematosus are very broad, and Dr. Dixit points out correctly that the diagnostic criteria developed by the American College of Rheumatology1,2 are not meant to be exclusive. Indeed, some children present with more isolated symptoms and then have multiorgan involvement later, all part of the same evolving chronic inflammatory disease.
In addition to allowing comparison of similar groups of patients, the presence of four of these criteria increases to more than 95 percent the sensitivity and specificity of a presumptive diagnosis of systemic lupus erythematosus versus another rheumatologic or systemic process.3 This should not be overlooked. Although fewer than four criteria would not have precluded a diagnosis, the presence of four criteria helped make systemic lupus erythematosus a much more likely putative diagnosis and helped tailor a further definitive diagnostic evaluation.
Dr. Sivagnanam is also correct that neither eosinophilia nor eosinophiluria is a sensitive or specific marker for an interstitial nephritis. In fact, only up to 30 percent of patients with a penicillin-induced interstitial nephritis (as would have to be posited as being the case in this child) present with eosinophilia in addition to fever and rash.4 However, with a case that involves a lengthy differential diagnosis, the presence of eosinophilia or eosinophiluria and associated systemic symptoms may help focus the evaluation.
Although it takes an average of 10 weeks for children to recover from acute renal failure due to all types of interstitial nephritis,5 renal function may stabilize or begin to improve sooner, especially once the offending agent is removed. Moreover, although the excretion of amoxicillin will be affected by renal failure, continuing to provide the antibiotic will probably exacerbate the situation and is clinically relevant as a functionally high dose.
We agree with Dr. Sivagnanam's distinction between the pharmacologic and clinical definitions of beta-blockers. However, labetalol can be and has been used successfully, as in this case, for its beta-blocker activity. We continue to use it successfully in this and other similar cases in our practice.
Michael J.G. Somers, M.D.
Children's Hospital
Boston, MA 02115
Ghaleb H. Daouk, M.D.
MassGeneral Hospital for Children
Boston, MA 02114
References
Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271-1277.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725-1725.
Niaudet P, Salomon R. Systemic lupus erythematosus. In: Avner ED, Harmon WE, Niaudet P, eds. Pediatric nephrology. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2004:865-86.
Appel GB. Acute interstitial nephritis. In: Neilson EG, Couser WG, eds. Immunologic renal diseases. Philadelphia: Lippincott-Raven, 1997:1221-34.
Ellis D, Fried WA, Yunis EJ, Blau EB. Acute interstitial nephritis in children: a report of 13 cases and review of the literature. Pediatrics 1981;67:862-870.
Rajiv K. Dixit, M.D.
Northern California Arthritis Center
Walnut Creek, CA 94598
References
Case Records of the Massachusetts General Hospital (Case 11-2004). N Engl J Med 2004;350:1550-1559.
Tan EM, Cohen A, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271-1277.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725-1725.
To the Editor: In Case 11-2004, the absence of eosinophiluria and lack of improvement on discontinuation of amoxicillin were cited in ruling out drug-induced nephritis. However, allergic interstitial nephritis is characterized by tubulointerstitial infiltration with granulocytes and typically, but not invariably, eosinophils.1 Furthermore, eosinophiluria is neither sensitive nor specific, and eosinophilia is seen only in one third of cases of acute interstitial nephritis.2 It generally takes about four to six weeks for the symptoms to resolve after discontinuation of drugs,3 and with renal failure, the half-life of amoxicillin increases by a factor of seven, leading to its retention.4 The temporal correlation of rash and renal failure after amoxicillin use, the absence of hematologic derangements (which are common in children with systemic lupus erythematosus but were not seen in this case), and specific tests for systemic lupus (e.g., a test for anti–double-stranded DNA antibodies) point more toward type III hypersensitivity, in my view.
The statement that labetalol is a selective beta-blocker is incorrect. It has alpha-blocking as well as beta-blocking properties, though its clinical effect is similar to that of a selective beta-blocker.4
G. Sivagnanam, M.D.
Chengalpattu Medical College
Chengalpattu 603 001, India
drsivagnanam@rediffmail.com
References
Brady HR, Brenner BM. Acute renal failure. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison's principles of internal medicine. 15th ed. Vol. 2. New York: McGraw Hill, 2001:1541-51.
Kher V, Arora P. Acute interstitial nephritis. In: Mandal AK, ed. Text book of nephrology for the Asian-Pacific physicians. 2nd ed. New Delhi, India: Jaypee Brothers, 2004:123-32.
Mathew C, Joshi VR. Systemic lupus erythematosus. In: Sen Gupta PC, ed. Clinical immunology. New Delhi, India: Oxford University Press, 2003:667-80.
Arterial hypertension, angina pectoris, myocardial infarction and kidney and urinary tract. In: Lawrence DR, Bennet PN, Brown MJ. Clinical pharmacology. 8th ed. Edinburgh: Churchill Livingstone, 1997:443, 484-99.
The authors reply: The clinical manifestations of systemic lupus erythematosus are very broad, and Dr. Dixit points out correctly that the diagnostic criteria developed by the American College of Rheumatology1,2 are not meant to be exclusive. Indeed, some children present with more isolated symptoms and then have multiorgan involvement later, all part of the same evolving chronic inflammatory disease.
In addition to allowing comparison of similar groups of patients, the presence of four of these criteria increases to more than 95 percent the sensitivity and specificity of a presumptive diagnosis of systemic lupus erythematosus versus another rheumatologic or systemic process.3 This should not be overlooked. Although fewer than four criteria would not have precluded a diagnosis, the presence of four criteria helped make systemic lupus erythematosus a much more likely putative diagnosis and helped tailor a further definitive diagnostic evaluation.
Dr. Sivagnanam is also correct that neither eosinophilia nor eosinophiluria is a sensitive or specific marker for an interstitial nephritis. In fact, only up to 30 percent of patients with a penicillin-induced interstitial nephritis (as would have to be posited as being the case in this child) present with eosinophilia in addition to fever and rash.4 However, with a case that involves a lengthy differential diagnosis, the presence of eosinophilia or eosinophiluria and associated systemic symptoms may help focus the evaluation.
Although it takes an average of 10 weeks for children to recover from acute renal failure due to all types of interstitial nephritis,5 renal function may stabilize or begin to improve sooner, especially once the offending agent is removed. Moreover, although the excretion of amoxicillin will be affected by renal failure, continuing to provide the antibiotic will probably exacerbate the situation and is clinically relevant as a functionally high dose.
We agree with Dr. Sivagnanam's distinction between the pharmacologic and clinical definitions of beta-blockers. However, labetalol can be and has been used successfully, as in this case, for its beta-blocker activity. We continue to use it successfully in this and other similar cases in our practice.
Michael J.G. Somers, M.D.
Children's Hospital
Boston, MA 02115
Ghaleb H. Daouk, M.D.
MassGeneral Hospital for Children
Boston, MA 02114
References
Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271-1277.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725-1725.
Niaudet P, Salomon R. Systemic lupus erythematosus. In: Avner ED, Harmon WE, Niaudet P, eds. Pediatric nephrology. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2004:865-86.
Appel GB. Acute interstitial nephritis. In: Neilson EG, Couser WG, eds. Immunologic renal diseases. Philadelphia: Lippincott-Raven, 1997:1221-34.
Ellis D, Fried WA, Yunis EJ, Blau EB. Acute interstitial nephritis in children: a report of 13 cases and review of the literature. Pediatrics 1981;67:862-870.