Michael Kassardjian, DO; Vanessa Holland, MD; Tracy Leong, MD;
David Horowitz, DO; Jane Hirokane, MD
Loma Linda University Medical Center, J.L. Pettit Veterans Administrative Hospital, Loma Linda California;
Western University of Health Sciences/Pacific Hospital of Long Beach Department of Dermatology, Long Beach, California
Disclosure: The authors report no relevant conflicts of interest.
Acute febrile neutrophilic dermatosis (Sweet’s syndrome) is typically characterized by an acute onset of erythematous papules, plaques, and nodules in a febrile patient. This dermatosis is classically accompanied by leukocytosis and neutrophilia, and has had reported associations with various underlying etiologies including drug reactions, malignancies, infections, autoimmune disorders, and inflammatory bowel diseases. However, most cases of acute febrile neutrophilic dermatosis are idiopathic. We present a unique case of Sweet’s syndrome in a patient with concurrent acute myocardial infarction. (J Clin Aesthet Dermatol. 2012;5(9):47–50.)
Acute febrile neutrophilic dermatosis, also known as Sweet’s syndrome, was first described by Dr. Robert Douglas Sweet in 1964 in reference to eight middle-aged women who had an acute onset of fever and erythematous plaques associated with a nonspecific infection of the respiratory or gastrointestinal tracts. Sweet’s syndrome is characterized by raised and painful erythematous papules, plaques, and nodules of rapid onset that are most commonly located on the face, neck, and upper extremities. The dermatosis is classically accompanied by fever, leukocytosis, and neutrophilia. Sweet’s syndrome presents in three clinical settings: idiopathic or classical, malignancy-associated, and drug-induced. The idiopathic subtype is the most common form of Sweet’s syndrome accounting for 80 to 90 percent of reported cases. The condition has been reported to follow viral infections and in association with autoimmune disorders, inflammatory bowel diseases, and pregnancy.
The authors present an unusual case of a patient who presented to the hospital with an acute myocardial infarction with a coincident cutaneous eruption that developed into Sweet’s syndrome in the subsequent days.
A 75-year-old Hispanic man with an extensive history of coronary artery disease was admitted to the Veterans Administration Hospital with a several-hour history of crushing chest pain and was unresponsive to sublingual nitroglycerin. On admission, he was noted to have an asymptomatic petechial rash on his abdomen and proximal extremities, which he reported noticing prior to the development of angina (Figure 1 and Figure 2). Over the ensuing few days, the rash progressed and became more verrucous on his extensor forearms; however, the cutaneous findings remained petechial on his trunk (Figure 3). The patient was otherwise afebrile throughout his hospital course. Several areas of the verrucous, crusted, and pustular plaques on his forearms were swabbed for bacterial culture, and were negative. Punch biopsies were performed on two thicker papules on the right forearm, one of which was submitted for tissue culture and the other for routine histochemistry. Biopsies performed were submitted for routine hematoxylin and eosin stain. The findings demonstrated a diffuse netrophilic infiltrate with marked dermal edema, suggestive of Sweet’s syndrome (Figures 4 and 5). Direct immunofluorescence was also performed to rule out a leukocytoclastic vasculitis and results were negative. With regard to his coronary condition, he was found to have a severe non-ST-elevation myocardial infarction that manifested worsening congestive heart failure complicated by acute renal failure. He subsequently progressed to multiorgan failure. Systemic corticosteroids to address the Sweet’s syndrome were held given the acute situation and his exhaustive comorbidities. On hospital Day 10, comfort measures were instituted as he refused dialysis and further intervention. He expired on hospital Day 12.
Sweet’s syndrome is considered to be a reactive phenomenon that should be considered a cutaneous marker for systemic disease. Classic or idiopathic Sweet’s syndrome is the most common presentation, accounting for 80 to 90 percent of cases.[4,7] This subset typically presents in women between 30 to 50 years of age with a preceding infection, most commonly of the upper respiratory tract. Streptococcal pneumonia is the most commonly reported infection. Other reported associated bacterial infections include Salmonella, Staphylococcus species, Yersinia enterocolitica, Entamoeba coli, Helicobacter pylori, Borrelia burgdorferi, Tuberculosis mycobacteria, and Mycobacterium chelonae.[6,8] Hepatitis A and B, cytomegalovirus (CMV), and human immunodeficiency virus (HIV) are viral agents that have also been reportedly associated with Sweet’s syndrome. The condition has also been reported in conjunction with various autoimmune disorders. Approximately 16 percent of patients with the so-termed idiopathic variant have an associated underlying inflammatory condition. Crohn’s disease and ulcerative colitis are the most commonly associated diseases; however, rheumatoid arthritis, lupus erythematosus, Sjogren’s syndrome, and Behcet’s disease have also been reported in association with Sweet’s syndrome. Relevant to the present case, Rodriguez-de la Serna described a case of Sweet’s syndrome that occurred in a patient with postmyocardial infarction syndrome (Dressler’s syndrome).
A hematological or solid tumor malignancy was found to represent 21 percent of patients with Sweet’s syndrome in a retrospective review of 15 studies done by Cohen and Kurzrock in 1993. Acute myelogenous leukemia is the most common malignancy associated with Sweet’s syndrome. Solid tumor carcinomas associated with Sweet’s syndrome patients include malignancies of the genitourinary organs, breast, and gastrointestinal tract.[14–17] In contrast to the idiopathic subset, malignancy-associated Sweet’s syndrome does not have a predilection toward females.
While representing less than five percent of cases, medications have been associated with the development of drug-induced Sweet’s syndrome. Most commonly, the administration of granulocyte-colony stimulating factor causes this variant of the dermatosis. Other drug reactions that have appeared in more than one case report include the following drugs: trimethoprim-sulfamethoxazole, all-trans retinoic acid, and minocycline. Although the patient described in this case had not been exposed to these medications, he had been receiving furosemide 40mg twice daily, which has been reported twice in the literature as attributing to Sweet’s syndrome. While drug-induced Sweet’s syndrome generally occurs acutely following only a few days after initiating a medication, the patient in this case had been receiving furosemide for several years prior to the development of the rash. The diagnostic criteria for drug-induced Sweet’s syndrome proposed by Walker et al include the following: abrupt onset of painful erythematous plaques or nodules, histopathological evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis, pyrexia (38oC), temporal relationship between drug ingestion and clinical presentation or temporally related recurrence after oral challenge, and temporally related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids. Unusual of Sweet’s syndrome, the patient in this case was afebrile on presentation and in the development of his lesions.
The classic histopathological findings of acute febrile neutrophilic dermatosis are dense, diffuse neutrophilic infiltrate in a band-like distribution within the upper and mid-dermis with leukocytoclastic nuclear debris interstitially, and frequently papillary dermal edema. True vasculitic changes are often absent. While nonspecific findings, such as spongiosis and subcorneal pustule formation may be observed in the epidermis, it usually is spared.
Management of Sweet’s syndrome varies depending on the underlying etiology. In the absence of any therapeutic intervention, cutaneous lesions and dermatosis-related symptoms may resolve spontaneously in some patients with classical Sweet’s syndrome. Sweet’s syndrome associated with malignancy typically remits following treatment or cure of the underlying carcinoma, while drug-induced Sweet’s syndrome improves spontaneously subsequent to cessation of the offending agent. However, in most cases of acute febrile neutrophilic dermatosis, prednisone is very effective at a dose of 1mg/kg/d. Additionally, high potency topical or intralesional steroids may be used to treat focal lesions.24 Suehisa and Tagami25 reported successful management of Sweet’s syndrome with colchicine in 1981, with numerous additional cases supporting its efficacy described since.[25,26] Successful treatment has also been noted in various small patient series with indomethacin, potassium iodide, cyclosporine, dapsone, and clofazimine.[2,7,27,28]
The patient in this case represents a unique presentation of Sweet’s syndrome yet to be reported in the literature. First, he was afebrile throughout his hospital course despite progression of the rash, atypical for Sweet’s syndrome, which is otherwise known as acute neutrophilic febrile dermatosis. Secondly, with regard to the temporal relationship, the cutaneous eruption coincided with his acute myocardial infarction suggesting that it was either reactive to or possibly precipitated the coronary event given his extensive underlying heart disease, also not yet described in the literature. The patient had declined screening colonoscopies, raising the possibility that he might have had an underlying gastrointestinal malignancy triggering the cutaneous eruption. However, gastrointestinal malignancies are not classically associated with Sweet’s syndrome, and had this been the case, the coincident development of myocardial infarction with the rash is difficult to explain. With all of the features of the present case taken together, the authors feel it represents an atypical afebrile Sweet’s syndrome reactive to or potentially precipitating an acute myocardial infarction.
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