Correspondence
Case 36-2007: A Woman with Rash, Fever, and Hypotension
N Engl J Med 2008; 358:1405-1407March 27, 2008
- Article
To the Editor:
In their discussion of a woman with rash, fever, and hypotension, Sabatine et al. (Nov. 22 issue)1 state that the patient was being treated with doxycycline for possible cellulitis of the face 2 days before admission. One day before admission, increased facial swelling, blurred vision, pelvic pain, and dysuria developed. The history, taken on admission, stated that the patient had a known allergy to doxycycline, which had caused “gastrointestinal distress, blurred vision, and a rash.” Given the temporal relationship between doxycycline administration and the fulminant heart failure that developed in the patient, and given that tetracyclines are among the medications implicated in hypersensitivity myocarditis, I am curious about why doxycycline was not considered the precipitating factor, rather than modafinil, in this patient.
1 ReferencesMonica Ghei, M.D.
Washington University School of Medicine, St. Louis, MO 63110
mghei@im.wustl. edu 1
Case Records of the Massachusetts General Hospital (Case 36-2007). N Engl J Med 2007;357:2167-2178
Full Text | Web of Science | Medline
To the Editor:
With regard to the discussion of acute inflammatory cardiomyopathies by Sabatine and colleagues, although initial treatment seemed to provide a benefit, it is unfortunate that the patient died as a result of a refractory ventricular tachyarrhythmia. It appears that a beta-blocker had been used earlier in her treatment but that she was unable to tolerate it later because of subsequent hypotension. I would suggest that beta-blockade is essential in such settings, however low the dosage may be (starting as low as 3.25 mg twice a day for carvedilol or 12.5 mg daily for extended-release metoprolol and slowly titrating upward to avoid hypotension), because the threshold for preventing malignant arrhythmias may be lower than that for a more effective hemodynamic circulatory response. In another form of inflammatory cardiomyopathy, peripartum cardiomyopathy, we have found the addition of beta-blockade to be particularly important in preventing deaths from early arrhythmias.1,2 Other centers also report improved survival and recovery with the addition of beta-blockade therapy.3 These results may also be seen with other fulminant inflammatory cardiomyopathies.4
4 ReferencesJames D. Fett, M.D., M.P.H.
Hôpital Albert Schweitzer, Deschapelles, Haiti
fett.sprunger@comcast. net 1
Fett JD ,Christie LG ,Carraway RD ,Murphy JG . Five-year prospective study of the incidence and prognosis of peripartum cardiomyopathy at a single institution. Mayo Clin Proc 2005;80:1602-1606
CrossRef | Web of Science | Medline2
Sliwa K ,Fett JD ,Elkayam U . Peripartum cardiomyopathy. Lancet 2006;368:687-693
CrossRef | Web of Science | Medline3
Palmer BA ,Janosko KM ,McTiernan C ,Sherman F ,McNamara DM . Left ventricular recovery in peripartum cardiomyopathy: impact of beta blockade. Circulation 2007;116:Suppl II:II-5514
Al Ali AM ,Straatman LP ,Allard MF ,Ignaszewski AP . Eosinophilic myocarditis: case series and review of literature. Can J Cardiol 2006;22:1233-1237
CrossRef | Web of Science | Medline
To the Editor:
Sabatine et al. report a case of a drug reaction with eosinophilia and systemic symptoms (DRESS) with fatal cardiac involvement. A total of 5% to 10% of patients with the DRESS syndrome may die because of systemic involvement, and this syndrome needs to be recognized quickly in order to discontinue the causative drug and look for life-threatening visceral manifestations, which are often treated with corticosteroids.1,2 Symptoms may persist or commence many days after the discontinuation of the culprit drug. Further flaring of the disease may develop later. DRESS also warrants long-term monitoring with slow tapering of corticosteroids.
Reactivation of human herpesvirus 6 (HHV-6) and 7 (HHV-7) occurs in both DRESS and multiple sclerosis.1-3 We recently reported a case of HHV-7 reactivation in a patient with both DRESS and multiple sclerosis.4 It would be of interest in this case to look for HHV-6 and HHV-7 reactivation in blood and cerebrospinal fluid samples and in heart tissue. An understanding of the role of HHV-6 in DRESS might be important in the management of this syndrome and might suggest the use of antiviral agents in addition to corticosteroids.
4 ReferencesVincent Descamps, M.D., Ph.D.
Bichat–Claude Bernard Hospital, 75018 Paris, France
vincent.descamps@bch. aphp. fr Pascal Joly, M.D., Ph.D.
Philippe Musette, M.D., Ph.D.
Rouen University Hospital, 76031 Rouen, France1
Descamps V ,Collot S ,Mahe E ,Houhou N ,Crickx B ,Ranger-Rogez S . Active human herpesvirus 6 infection in a patient with drug rash with eosinophilia and systemic symptoms. J Invest Dermatol 2003;121:215-216
CrossRef | Web of Science | Medline2
Tohyama M ,Hashimoto K ,Yasukawa M , et al. Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome. Br J Dermatol 2007;157:934-940
CrossRef | Web of Science | Medline3
Alvarez-Lafuente R ,de las Heras V ,Garcia-Montojo M ,Bartolome M ,Arroyo R . Human herpesvirus-6 and multiple sclerosis: relapsing-remitting versus secondary progressive. Mult Scler 2007;13:578-583
CrossRef | Web of Science | Medline4
Descamps V ,Alexandra J ,Papo T ,Crickx B . Syndrome d'hypersensibilité médicamenteuse (DRESS) à la carbamazépine au cours d'une sclérose en plaques avec réactivation HHV7: deux maladies associées à l'infection HHV7. Ann Dermatol Venereol 2007;134:7S234-7S234
CrossRef | Web of Science
To the Editor:
In eosinophilic myocarditis, the damage to cardiomyocytes is induced by the release of basic eosinophil proteins, including major basic protein, cationic protein, and peroxidase.1 A case report indicates that a new drug, suplatast tosilate, has been successfully used to treat acute eosinophilic myocarditis that was resistant to conventional prednisolone treatment.2 Suplatast, a dimethyl sulfoxide agent, is a selective type 2 helper T-cell (Th2) cytokine inhibitor3 that suppresses interleukin-4–induced expression of vascular-cell adhesion molecule 1 on endothelial cells, decreasing adhesion and platelet-activating factor–induced eosinophil chemotaxis and thus decreasing eosinophil infiltration of the inflamed tissue.4
4 ReferencesMuhammad A. Mir, M.B., B.S.
Fareeha Khalil, M.B., B.S.
University at Buffalo, Buffalo, NY 14212
mmir@buffalo.edu 1
Touze JE ,Fourcade L ,Heno P ,Mafart B ,Mourot S . The heart and the eosinophil. Med Trop (Mars) 1998;58:Suppl:459-464
Medline2
Umemoto S ,Itagaki K ,Kimura M , et al. Effect of suplatast tosilate, an antiallergic selective Th2 cytokine inhibitor, on acute eosinophilic myocarditis: a case report. Heart Vessels 2003;18:100-102
CrossRef | Web of Science | Medline3
Oda N ,Minoguchi K ,Tanaka A , et al. Suplatast tosilate inhibits thymus- and activation-regulated chemokine production by antigen-specific human Th2 cells. Clin Exp Allergy 2002;32:1782-1786
CrossRef | Web of Science | Medline4
Suwaki T ,Agarwal DK ,Townley RG . Modification of eosinophil function by suplatast tosilate (IPD), a novel anti-allergic drug. Int Immunopharmacol 2001;1:2163-2171
CrossRef | Web of Science | Medline
Author/Editor Response
Ghei asks why doxycycline was not considered the cause of the patient's hypersensitivity reaction. In hypersensitivity reactions, causality is typically inferred on the basis of the temporal sequence. In this patient, a rash developed and, eventually, swelling of the left side of the jaw after she received modafinil. Doxycycline was then prescribed in response to these developments. Examination of a fine-needle aspirate from the left masseter muscle revealed eosinophils, suggesting that the hypersensitivity reaction preceded the use of doxycycline, although we cannot rule out a further reaction in response to doxycycline or any of the other medications she received.
Fett, extrapolating from data concerning peripartum and other inflammatory cardiomyopathies, suggests that our patient might have benefited from beta-blockade. Beta-blockers are indicated in patients with compensated, but not decompensated heart failure.1 Acute necrotizing eosinophilic myocarditis presents with a much greater degree of myocardial injury than is typically seen in peripartum cardiomyopathy. Consistent with this pattern, the patient described in our article required support with a beta-agonist inotrope to maintain adequate cardiac output. A beta-blocker is contraindicated in that setting.1
Descamps and colleagues note reports describing the reactivation of HHV-6 and HHV-7 in patients with multiple sclerosis and drug-associated hypersensitivity reactions. However, most people, if not all, are infected with HHV-6 and HHV-7 during childhood.2 There is no solid evidence that these viruses play a causal role in either of these conditions, and their reactivation could simply be a consequence of immune activation. Therefore, although testing for the reactivation of HHV-6 and HHV-7 in the patient described in our report might be interesting, the significance of any positive findings would be unclear.
Suplatast tosilate is a relatively new medication that has been reported to have inhibitory effects on Th2 cytokine signaling. The medication's mechanism of action is not known, and it has not been approved by the Food and Drug Administration.3 Mir and Khalil cite an intriguing report from Japan concerning a patient with subacute eosinophilic myocarditis with a preserved ejection fraction in whom the addition of suplatast to a prednisolone taper was associated with a reduction in inflammatory biomarkers.4 However, suplatast appears to have a relatively delayed effect,3 and in the cited report the agent was administered approximately 2 months after the diagnosis of myocarditis, with the effects observed 4 months later.4 It is not known whether suplatast has clinical efficacy in patients with acute necrotizing eosinophilic myocarditis such as the patient described in our report.
4 ReferencesMarc S. Sabatine, M.D., M.P.H.
Brigham and Women's Hospital, Boston, MA 02115Jessica L. Mega, M.D.
James R. Stone, M.D., Ph.D.
Massachusetts General Hospital, Boston, MA 021151
Hunt SA ,Abraham WT ,Chin MH , et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 2005;112:e154-e235
CrossRef | Web of Science | Medline2
Ward KN . Human herpesviruses-6 and -7 infections. Curr Opin Infect Dis 2005;18:247-252
CrossRef | Web of Science | Medline3
Sano Y ,Yamada H . Progress in suplatast tosilate research. Clin Exp Allergy 2007;37:970-972
CrossRef | Web of Science | Medline4
Umemoto S ,Itagaki K ,Kimura M , et al. Effect of suplatast tosilate, an antiallergic selective Th2 cytokine inhibitor, on acute eosinophilic myocarditis: a case report. Heart Vessels 2003;18:100-102
CrossRef | Web of Science | Medline
