Patient Presentation A 38-year-old Caucasian woman presented with a 3-day history of fever, fatigue and arthralgias, symptoms that were associated with the abrupt development of tender, hot nodules, papules and plaques on the trunk and extremities. The patient reported a history of streptococcal pharyngitis for which she completed a course of amoxicillin 10 days prior to developing her current symptoms. On physical examination there were multiple edematous, erythematous to violaceous plaques, some with central pustules, distributed over the chest and upper and lower extremities. Some of these plaques were studded with vesicles and pustules, and several appeared along scratch marks.
What’s Your Diagnosis?
HISTORICAL NOTE ON SWEET’S SYNDROME
Robert Douglas Sweet first described Sweet’s syndrome (SS) in England in 1964.1 It was initially known in his department as the Gomm-Button disease in eponymous honor of the first two patients with the condition. Subsequently, SS has become the established eponym for this dermatosis despite Dr. Sweet’s recommendation that the name remain descriptive.1 In regard to our patient, the appearance of lesions along cat scratch marks and other areas of trauma is typical of the Koebner, or isomorphic, phenomenon. Laboratory studies showed a leukocytosis with marked neutrophilia and an erythrocyte sedimentation rate of 80 mm/hr. Antistreptodornase antibodies were also elevated. A skin biopsy of a plaque on her arm showed a dense superficial neutrophilic infiltrate in the dermis extending into the epidermis, consistent with SS. She defervesced, the rash improved, and other symptoms resolved shortly after starting a tapering course of oral prednisone beginning at 60 mg per day.
A BRIEF NOTE ON THE EPIDEMIOLOGY AND ETIOLOGY OF SS
The syndrome has been shown to exist worldwide and show no racial preference. SS primarily affects patients between the ages of 30 to 50 years, although cases in younger patients have also been reported.2 SS demonstrates a female to male ratio of 3:1. The precise cause of SS is unknown. It is believed that SS could be a reactive process in response to systemic factors, including hematologic disease, infection or drug exposure. The latter is most consistent with our patient’s case, with her eruption having developed as a reaction to the amoxicillin taken for treatment of streptococcal pharyngitis.
CLINICAL MANIFESTATIONS
Several types of SS exist, which include the following:
• classic type (71%)
• forms associated with inflammatory disease (16%)
• forms secondary to malignancies (11%)
• types associated with pregnancy (2%)3
• form associated with a drug-induced reaction (as mentioned in this patient’s case).
Classic SS usually occurs in young women after mild respiratory illness, such as an upper respiratory tract infection, tonsillitis, or a flu-like syndrome, 1 to 3 weeks prior to the onset of skin lesions. Patients often present with fever and leukocytosis, but antibiotics do not seem to alleviate these symptoms. Additional symptoms may include headache, arthralgias, conjunctivitis, and episcleritis.4 Myalgias, arthritis, conjunctivitis, and renal involvement are also common features.5 Clinical findings include the appearance of reddish-blue painful nodules, which may be “studded” with pustules and papules, and often coalesce into 2-cm to 10-cm circinate or arcuate plaques.6 Various forms of lesions have been described, including superficial vesicles, bullae and ulcers. The most commonly affected sites are the face, forearms and neck, with an asymmetrical distribution. The hands, arms and lower limbs may also be involved.
Widespread lesions have been reported, but lesions of the trunk are uncommon. Lesions may occur at sites of minor trauma, such as bites, scratches and venipuncture. Our patient developed lesions at sites of scratch from a cat. Onset can be abrupt and lesions may rapidly increase in size. Mucosal surfaces can be affected as well, but oral involvement is not common. Conjunctivitis and episcleritis are the most commonly noted eye manifestations. The more aggressive type of SS occurs as a neutrophilic process that may be associated with inflammatory diseases or malignancies. The most common malignant disease affecting patients with SS is acute myelogenous leukemia (AML), while others include genitourinary, breast, and gastrointestinal cancers.7 SS may occur in association with other hematopoietic disorders, malignant lesions, paraproteinemia, inflammatory bowel disease, rheumatologic disease, pregnancy, infection and other systemic disorders.8 Medication-induced SS has been reported most frequently following treatment with granulocyte-colony stimulating factor,2 as well as with the use of various medications including carbamazepine, furosemide, trimethoprim-sulfamethoxazole, and minocycline.9 Although the skin is the primary organ affected, SS has the potential to involve several other organ systems, most notably the lung and kidney. Pulmonary manifestations are the most common findings, although proteinuria, hematuria, and decreased creatinine clearance may also be seen.
HISTOLOGICAL MANIFESTATIONS
The classic histopathologic pattern consists of a dense, diffuse neutrophilic infiltrate in the reticular dermis, with edema in the upper dermis. The infiltrate is initially perivascular, yet may become dense and widespread throughout the dermis and occasionally into the subcutis, with infiltration of mature polymorphonuclear leukocytes, mononuclear cells and eosinophils. Capillaries show endothelial swelling with some leukocytoclasia but no frank vasculitis. The epidermis usually is intact.
LABORATORY INVESTIGATIONS
A complete blood cell count is obtained to screen for underlying hematologic disorders. Neutrophilia is typically present, and peripheral white blood cell count is elevated in the range of 10,000/ml to 18,000/ml, with 80% to 85% polymorphonuclear leukocytes. Anemia and thrombocytopenia are commonly seen, and an elevated erythrocyte sedimentation rate is found in more than 90% of cases. Proteinuria can be seen on urinalysis and hepatic enzyme levels may also be elevated. Imaging studies including chest X-ray should be performed if pulmonary symptoms are present, as well as bone marrow aspiration if complete blood count findings are abnormal.
DIFFERENT CRITERIA FOR DIAGNOSING SS
In 1964, Robert Douglas Sweet initially characterized the disorder as an acute eruption of painful erythematous plaques and nodules usually associated with fever, leukocytosis, and a dense papillary dermal neutrophilic infiltrate in middle-aged women.1 In 1986, Su and Liu put forth several parameters for diagnosis of SS, including major and minor criteria.10 Then in 1989, von den Driesch and associates added an additional minor criterion to Su and Liu’s diagnosis guide: an increased erythrocyte sedimentation rate.11 Finally, in 1996, Walker and Cohen proposed their own criteria for SS. All four major criteria and two minor clinical findings must be met as well.12 Major criteria:
1. Acute onset of tender or painful erythematous plaques or nodules, occasionally with vesicles, pustules, or bullae.
2. Histopathological evidence of a dense neutrophilic infiltrate without leukocytoclastic vasculitis.
3. Fever >100.4°F (38°C).
4. Reappearance of lesions after drug treatment with corticosteroids.
Minor criteria:
1. Skin eruption preceded by a nonspecific respiratory or gastrointestinal tract infection (febrile upper respiratory tract infection, tonsillitis, or influenza-like illness) or vaccination or association with inflammatory disease, hemoproliferative disorders, solid malignant tumors, or pregnancy.
2. Eruption accompanied by periods of general malaise and fever >100.4°F (38°C).
3. Laboratory values during onset of erythrocyte sedimentation rate >20 mm, C-reactive protein positive, segmented nuclear neutrophils and bands greater than 70% in peripheral blood smear, and leukocytosis more than 8,000.
4. Excellent response to treatment with systemic corticosteroids or potassium iodide.
Diagnostic criteria for drug-induced SS include the first three major criteria listed above, in addition to a temporal relationship between drug ingestion/challenge and development or recurrence of the syndrome, as well as symptom resolution after drug withdrawal or corticosteroid administration.2
DIFFERENTIAL DIAGNOSIS
Behçet’s disease is a chronic multisystem disease characterized by ulcerations in the mouth and genitalia, iritis, uveitis, arthritis and thrombophlebitis. HLA B51 is frequently found in patients with Behçet’s disease while HLA B54 is more frequent with SS and rare in Behçet’s disease.13 Corticosteroid therapy may aggravate symptoms in Behçet’s disease, while improving those in SS.13 Drug eruptions have also been implicated in the causation of SS, including the selective cyclo-oxygenase-2 (COX-2) inhibitor celecoxib (Celebrex) and granulocyte colony-stimulating factor.14,15 Both erythema nodosum and SS may occur as reactions to an antecedent viral or bacterial illnesses. The anterior legs are an uncommon site for SS, but it is not unusual for both disease processes to occur concurrently in the same individual. Pyoderma gangrenosum usually begins as a soft nodule on the skin which proceeds to ulcerate. Lesions may follow mild trauma, ulcerations may extend rapidly within a few days and new lesions may appear as older ones resolve.16 Pyoderma gangrenosum is usually responsive to corticosteroids. The differential diagnosis of SS also includes other severe inflammatory and infectious disorders, bowel bypass-related dermatosis, vasculitis, cellulitis, and neoplastic processes (leukemia cutis, lymphoma and metastatic tumor).17,18
MANAGEMENT and TREATMENT
Systemic corticosteroids have been the treatment of choice in most large series of patients reported.8 In most cases, prednisone is extremely and rapidly effective, in doses ranging from 40 mg to 80 mg per day. However, despite the initial excellent response, recurrences of neutrophilic dermatosis are common in 25% of cases and generally develop as steroids are being tapered.19 Topical and intralesional corticosteroids have also been used along with systemic corticosteroids. Occasionally, they are used alone. For long-term management, non-steroidal anti-inflammatory agents such as indomethacin are used as an alternative to corticosteroids. Indomethacin at 150 mg/day for 1 week and 100 mg/day for 2 weeks may alleviate symptoms such as fever and arthralgia within 48 hours and skin lesions within 1 to 2 weeks. Potassium Iodide may also be as effective as corticosteroids.9,11 Colchicine has also been shown effective in a few case reports. However, others found it to be ineffective.8 Dapsone at 100 mg to 200 mg per day has been demonstrated in a few cases as an effective agent in SS, its mechanism being inhibition of bacterial growth and interference with neutrophil infiltration and adherence.8 Cyclosporine, etretinate, doxycycline, clofazamine, pentoxifylline, and the TNF-alpha inhibitor infliximab have also been used with success.2
PROGNOSIS
Since SS may be associated with many other disease processes, prognosis depends on the specific underlying cause, and relapse may occur in up to 50% of patients.6 Recurrence has been reported to most likely occur in conjunction with infections; hematopoietic, lymphoid, and plasma cell disorders; malignant diseases, and various other systemic conditions.20 Hence, it is important to recognize and treat any associated or underlying systemic diseases or malignancies, as SS can serve as a clue to their diagnoses. Most cases of acute neutrophilic dermatosis resolve, although some may persist indefinitely and can be very difficult to manage because of pain and skin breakdown.6 The duration of the lesions in SS original series ranged from 6 weeks to 6 months. This syndrome responds to systemic steroids within few days.8 Untreated, it is seen that most cases will undergo spontaneous remission within 6 to 8 weeks, but rapid spontaneous remission within 2 weeks may also be seen. Some lesions resolve without scarring, although pigmentary changes may take months to resolve. Sweet’s can occur during pregnancy and recur in subsequent pregnancies. Presently, it is believed that the disease is not a threat to the fetus.
Patient Presentation A 38-year-old Caucasian woman presented with a 3-day history of fever, fatigue and arthralgias, symptoms that were associated with the abrupt development of tender, hot nodules, papules and plaques on the trunk and extremities. The patient reported a history of streptococcal pharyngitis for which she completed a course of amoxicillin 10 days prior to developing her current symptoms. On physical examination there were multiple edematous, erythematous to violaceous plaques, some with central pustules, distributed over the chest and upper and lower extremities. Some of these plaques were studded with vesicles and pustules, and several appeared along scratch marks.
What’s Your Diagnosis?
HISTORICAL NOTE ON SWEET’S SYNDROME
Robert Douglas Sweet first described Sweet’s syndrome (SS) in England in 1964.1 It was initially known in his department as the Gomm-Button disease in eponymous honor of the first two patients with the condition. Subsequently, SS has become the established eponym for this dermatosis despite Dr. Sweet’s recommendation that the name remain descriptive.1 In regard to our patient, the appearance of lesions along cat scratch marks and other areas of trauma is typical of the Koebner, or isomorphic, phenomenon. Laboratory studies showed a leukocytosis with marked neutrophilia and an erythrocyte sedimentation rate of 80 mm/hr. Antistreptodornase antibodies were also elevated. A skin biopsy of a plaque on her arm showed a dense superficial neutrophilic infiltrate in the dermis extending into the epidermis, consistent with SS. She defervesced, the rash improved, and other symptoms resolved shortly after starting a tapering course of oral prednisone beginning at 60 mg per day.
A BRIEF NOTE ON THE EPIDEMIOLOGY AND ETIOLOGY OF SS
The syndrome has been shown to exist worldwide and show no racial preference. SS primarily affects patients between the ages of 30 to 50 years, although cases in younger patients have also been reported.2 SS demonstrates a female to male ratio of 3:1. The precise cause of SS is unknown. It is believed that SS could be a reactive process in response to systemic factors, including hematologic disease, infection or drug exposure. The latter is most consistent with our patient’s case, with her eruption having developed as a reaction to the amoxicillin taken for treatment of streptococcal pharyngitis.
CLINICAL MANIFESTATIONS
Several types of SS exist, which include the following:
• classic type (71%)
• forms associated with inflammatory disease (16%)
• forms secondary to malignancies (11%)
• types associated with pregnancy (2%)3
• form associated with a drug-induced reaction (as mentioned in this patient’s case).
Classic SS usually occurs in young women after mild respiratory illness, such as an upper respiratory tract infection, tonsillitis, or a flu-like syndrome, 1 to 3 weeks prior to the onset of skin lesions. Patients often present with fever and leukocytosis, but antibiotics do not seem to alleviate these symptoms. Additional symptoms may include headache, arthralgias, conjunctivitis, and episcleritis.4 Myalgias, arthritis, conjunctivitis, and renal involvement are also common features.5 Clinical findings include the appearance of reddish-blue painful nodules, which may be “studded” with pustules and papules, and often coalesce into 2-cm to 10-cm circinate or arcuate plaques.6 Various forms of lesions have been described, including superficial vesicles, bullae and ulcers. The most commonly affected sites are the face, forearms and neck, with an asymmetrical distribution. The hands, arms and lower limbs may also be involved.
Widespread lesions have been reported, but lesions of the trunk are uncommon. Lesions may occur at sites of minor trauma, such as bites, scratches and venipuncture. Our patient developed lesions at sites of scratch from a cat. Onset can be abrupt and lesions may rapidly increase in size. Mucosal surfaces can be affected as well, but oral involvement is not common. Conjunctivitis and episcleritis are the most commonly noted eye manifestations. The more aggressive type of SS occurs as a neutrophilic process that may be associated with inflammatory diseases or malignancies. The most common malignant disease affecting patients with SS is acute myelogenous leukemia (AML), while others include genitourinary, breast, and gastrointestinal cancers.7 SS may occur in association with other hematopoietic disorders, malignant lesions, paraproteinemia, inflammatory bowel disease, rheumatologic disease, pregnancy, infection and other systemic disorders.8 Medication-induced SS has been reported most frequently following treatment with granulocyte-colony stimulating factor,2 as well as with the use of various medications including carbamazepine, furosemide, trimethoprim-sulfamethoxazole, and minocycline.9 Although the skin is the primary organ affected, SS has the potential to involve several other organ systems, most notably the lung and kidney. Pulmonary manifestations are the most common findings, although proteinuria, hematuria, and decreased creatinine clearance may also be seen.
HISTOLOGICAL MANIFESTATIONS
The classic histopathologic pattern consists of a dense, diffuse neutrophilic infiltrate in the reticular dermis, with edema in the upper dermis. The infiltrate is initially perivascular, yet may become dense and widespread throughout the dermis and occasionally into the subcutis, with infiltration of mature polymorphonuclear leukocytes, mononuclear cells and eosinophils. Capillaries show endothelial swelling with some leukocytoclasia but no frank vasculitis. The epidermis usually is intact.
LABORATORY INVESTIGATIONS
A complete blood cell count is obtained to screen for underlying hematologic disorders. Neutrophilia is typically present, and peripheral white blood cell count is elevated in the range of 10,000/ml to 18,000/ml, with 80% to 85% polymorphonuclear leukocytes. Anemia and thrombocytopenia are commonly seen, and an elevated erythrocyte sedimentation rate is found in more than 90% of cases. Proteinuria can be seen on urinalysis and hepatic enzyme levels may also be elevated. Imaging studies including chest X-ray should be performed if pulmonary symptoms are present, as well as bone marrow aspiration if complete blood count findings are abnormal.
DIFFERENT CRITERIA FOR DIAGNOSING SS
In 1964, Robert Douglas Sweet initially characterized the disorder as an acute eruption of painful erythematous plaques and nodules usually associated with fever, leukocytosis, and a dense papillary dermal neutrophilic infiltrate in middle-aged women.1 In 1986, Su and Liu put forth several parameters for diagnosis of SS, including major and minor criteria.10 Then in 1989, von den Driesch and associates added an additional minor criterion to Su and Liu’s diagnosis guide: an increased erythrocyte sedimentation rate.11 Finally, in 1996, Walker and Cohen proposed their own criteria for SS. All four major criteria and two minor clinical findings must be met as well.12 Major criteria:
1. Acute onset of tender or painful erythematous plaques or nodules, occasionally with vesicles, pustules, or bullae.
2. Histopathological evidence of a dense neutrophilic infiltrate without leukocytoclastic vasculitis.
3. Fever >100.4°F (38°C).
4. Reappearance of lesions after drug treatment with corticosteroids.
Minor criteria:
1. Skin eruption preceded by a nonspecific respiratory or gastrointestinal tract infection (febrile upper respiratory tract infection, tonsillitis, or influenza-like illness) or vaccination or association with inflammatory disease, hemoproliferative disorders, solid malignant tumors, or pregnancy.
2. Eruption accompanied by periods of general malaise and fever >100.4°F (38°C).
3. Laboratory values during onset of erythrocyte sedimentation rate >20 mm, C-reactive protein positive, segmented nuclear neutrophils and bands greater than 70% in peripheral blood smear, and leukocytosis more than 8,000.
4. Excellent response to treatment with systemic corticosteroids or potassium iodide.
Diagnostic criteria for drug-induced SS include the first three major criteria listed above, in addition to a temporal relationship between drug ingestion/challenge and development or recurrence of the syndrome, as well as symptom resolution after drug withdrawal or corticosteroid administration.2
DIFFERENTIAL DIAGNOSIS
Behçet’s disease is a chronic multisystem disease characterized by ulcerations in the mouth and genitalia, iritis, uveitis, arthritis and thrombophlebitis. HLA B51 is frequently found in patients with Behçet’s disease while HLA B54 is more frequent with SS and rare in Behçet’s disease.13 Corticosteroid therapy may aggravate symptoms in Behçet’s disease, while improving those in SS.13 Drug eruptions have also been implicated in the causation of SS, including the selective cyclo-oxygenase-2 (COX-2) inhibitor celecoxib (Celebrex) and granulocyte colony-stimulating factor.14,15 Both erythema nodosum and SS may occur as reactions to an antecedent viral or bacterial illnesses. The anterior legs are an uncommon site for SS, but it is not unusual for both disease processes to occur concurrently in the same individual. Pyoderma gangrenosum usually begins as a soft nodule on the skin which proceeds to ulcerate. Lesions may follow mild trauma, ulcerations may extend rapidly within a few days and new lesions may appear as older ones resolve.16 Pyoderma gangrenosum is usually responsive to corticosteroids. The differential diagnosis of SS also includes other severe inflammatory and infectious disorders, bowel bypass-related dermatosis, vasculitis, cellulitis, and neoplastic processes (leukemia cutis, lymphoma and metastatic tumor).17,18
MANAGEMENT and TREATMENT
Systemic corticosteroids have been the treatment of choice in most large series of patients reported.8 In most cases, prednisone is extremely and rapidly effective, in doses ranging from 40 mg to 80 mg per day. However, despite the initial excellent response, recurrences of neutrophilic dermatosis are common in 25% of cases and generally develop as steroids are being tapered.19 Topical and intralesional corticosteroids have also been used along with systemic corticosteroids. Occasionally, they are used alone. For long-term management, non-steroidal anti-inflammatory agents such as indomethacin are used as an alternative to corticosteroids. Indomethacin at 150 mg/day for 1 week and 100 mg/day for 2 weeks may alleviate symptoms such as fever and arthralgia within 48 hours and skin lesions within 1 to 2 weeks. Potassium Iodide may also be as effective as corticosteroids.9,11 Colchicine has also been shown effective in a few case reports. However, others found it to be ineffective.8 Dapsone at 100 mg to 200 mg per day has been demonstrated in a few cases as an effective agent in SS, its mechanism being inhibition of bacterial growth and interference with neutrophil infiltration and adherence.8 Cyclosporine, etretinate, doxycycline, clofazamine, pentoxifylline, and the TNF-alpha inhibitor infliximab have also been used with success.2
PROGNOSIS
Since SS may be associated with many other disease processes, prognosis depends on the specific underlying cause, and relapse may occur in up to 50% of patients.6 Recurrence has been reported to most likely occur in conjunction with infections; hematopoietic, lymphoid, and plasma cell disorders; malignant diseases, and various other systemic conditions.20 Hence, it is important to recognize and treat any associated or underlying systemic diseases or malignancies, as SS can serve as a clue to their diagnoses. Most cases of acute neutrophilic dermatosis resolve, although some may persist indefinitely and can be very difficult to manage because of pain and skin breakdown.6 The duration of the lesions in SS original series ranged from 6 weeks to 6 months. This syndrome responds to systemic steroids within few days.8 Untreated, it is seen that most cases will undergo spontaneous remission within 6 to 8 weeks, but rapid spontaneous remission within 2 weeks may also be seen. Some lesions resolve without scarring, although pigmentary changes may take months to resolve. Sweet’s can occur during pregnancy and recur in subsequent pregnancies. Presently, it is believed that the disease is not a threat to the fetus.
Patient Presentation A 38-year-old Caucasian woman presented with a 3-day history of fever, fatigue and arthralgias, symptoms that were associated with the abrupt development of tender, hot nodules, papules and plaques on the trunk and extremities. The patient reported a history of streptococcal pharyngitis for which she completed a course of amoxicillin 10 days prior to developing her current symptoms. On physical examination there were multiple edematous, erythematous to violaceous plaques, some with central pustules, distributed over the chest and upper and lower extremities. Some of these plaques were studded with vesicles and pustules, and several appeared along scratch marks.
What’s Your Diagnosis?
HISTORICAL NOTE ON SWEET’S SYNDROME
Robert Douglas Sweet first described Sweet’s syndrome (SS) in England in 1964.1 It was initially known in his department as the Gomm-Button disease in eponymous honor of the first two patients with the condition. Subsequently, SS has become the established eponym for this dermatosis despite Dr. Sweet’s recommendation that the name remain descriptive.1 In regard to our patient, the appearance of lesions along cat scratch marks and other areas of trauma is typical of the Koebner, or isomorphic, phenomenon. Laboratory studies showed a leukocytosis with marked neutrophilia and an erythrocyte sedimentation rate of 80 mm/hr. Antistreptodornase antibodies were also elevated. A skin biopsy of a plaque on her arm showed a dense superficial neutrophilic infiltrate in the dermis extending into the epidermis, consistent with SS. She defervesced, the rash improved, and other symptoms resolved shortly after starting a tapering course of oral prednisone beginning at 60 mg per day.
A BRIEF NOTE ON THE EPIDEMIOLOGY AND ETIOLOGY OF SS
The syndrome has been shown to exist worldwide and show no racial preference. SS primarily affects patients between the ages of 30 to 50 years, although cases in younger patients have also been reported.2 SS demonstrates a female to male ratio of 3:1. The precise cause of SS is unknown. It is believed that SS could be a reactive process in response to systemic factors, including hematologic disease, infection or drug exposure. The latter is most consistent with our patient’s case, with her eruption having developed as a reaction to the amoxicillin taken for treatment of streptococcal pharyngitis.
CLINICAL MANIFESTATIONS
Several types of SS exist, which include the following:
• classic type (71%)
• forms associated with inflammatory disease (16%)
• forms secondary to malignancies (11%)
• types associated with pregnancy (2%)3
• form associated with a drug-induced reaction (as mentioned in this patient’s case).
Classic SS usually occurs in young women after mild respiratory illness, such as an upper respiratory tract infection, tonsillitis, or a flu-like syndrome, 1 to 3 weeks prior to the onset of skin lesions. Patients often present with fever and leukocytosis, but antibiotics do not seem to alleviate these symptoms. Additional symptoms may include headache, arthralgias, conjunctivitis, and episcleritis.4 Myalgias, arthritis, conjunctivitis, and renal involvement are also common features.5 Clinical findings include the appearance of reddish-blue painful nodules, which may be “studded” with pustules and papules, and often coalesce into 2-cm to 10-cm circinate or arcuate plaques.6 Various forms of lesions have been described, including superficial vesicles, bullae and ulcers. The most commonly affected sites are the face, forearms and neck, with an asymmetrical distribution. The hands, arms and lower limbs may also be involved.
Widespread lesions have been reported, but lesions of the trunk are uncommon. Lesions may occur at sites of minor trauma, such as bites, scratches and venipuncture. Our patient developed lesions at sites of scratch from a cat. Onset can be abrupt and lesions may rapidly increase in size. Mucosal surfaces can be affected as well, but oral involvement is not common. Conjunctivitis and episcleritis are the most commonly noted eye manifestations. The more aggressive type of SS occurs as a neutrophilic process that may be associated with inflammatory diseases or malignancies. The most common malignant disease affecting patients with SS is acute myelogenous leukemia (AML), while others include genitourinary, breast, and gastrointestinal cancers.7 SS may occur in association with other hematopoietic disorders, malignant lesions, paraproteinemia, inflammatory bowel disease, rheumatologic disease, pregnancy, infection and other systemic disorders.8 Medication-induced SS has been reported most frequently following treatment with granulocyte-colony stimulating factor,2 as well as with the use of various medications including carbamazepine, furosemide, trimethoprim-sulfamethoxazole, and minocycline.9 Although the skin is the primary organ affected, SS has the potential to involve several other organ systems, most notably the lung and kidney. Pulmonary manifestations are the most common findings, although proteinuria, hematuria, and decreased creatinine clearance may also be seen.
HISTOLOGICAL MANIFESTATIONS
The classic histopathologic pattern consists of a dense, diffuse neutrophilic infiltrate in the reticular dermis, with edema in the upper dermis. The infiltrate is initially perivascular, yet may become dense and widespread throughout the dermis and occasionally into the subcutis, with infiltration of mature polymorphonuclear leukocytes, mononuclear cells and eosinophils. Capillaries show endothelial swelling with some leukocytoclasia but no frank vasculitis. The epidermis usually is intact.
LABORATORY INVESTIGATIONS
A complete blood cell count is obtained to screen for underlying hematologic disorders. Neutrophilia is typically present, and peripheral white blood cell count is elevated in the range of 10,000/ml to 18,000/ml, with 80% to 85% polymorphonuclear leukocytes. Anemia and thrombocytopenia are commonly seen, and an elevated erythrocyte sedimentation rate is found in more than 90% of cases. Proteinuria can be seen on urinalysis and hepatic enzyme levels may also be elevated. Imaging studies including chest X-ray should be performed if pulmonary symptoms are present, as well as bone marrow aspiration if complete blood count findings are abnormal.
DIFFERENT CRITERIA FOR DIAGNOSING SS
In 1964, Robert Douglas Sweet initially characterized the disorder as an acute eruption of painful erythematous plaques and nodules usually associated with fever, leukocytosis, and a dense papillary dermal neutrophilic infiltrate in middle-aged women.1 In 1986, Su and Liu put forth several parameters for diagnosis of SS, including major and minor criteria.10 Then in 1989, von den Driesch and associates added an additional minor criterion to Su and Liu’s diagnosis guide: an increased erythrocyte sedimentation rate.11 Finally, in 1996, Walker and Cohen proposed their own criteria for SS. All four major criteria and two minor clinical findings must be met as well.12 Major criteria:
1. Acute onset of tender or painful erythematous plaques or nodules, occasionally with vesicles, pustules, or bullae.
2. Histopathological evidence of a dense neutrophilic infiltrate without leukocytoclastic vasculitis.
3. Fever >100.4°F (38°C).
4. Reappearance of lesions after drug treatment with corticosteroids.
Minor criteria:
1. Skin eruption preceded by a nonspecific respiratory or gastrointestinal tract infection (febrile upper respiratory tract infection, tonsillitis, or influenza-like illness) or vaccination or association with inflammatory disease, hemoproliferative disorders, solid malignant tumors, or pregnancy.
2. Eruption accompanied by periods of general malaise and fever >100.4°F (38°C).
3. Laboratory values during onset of erythrocyte sedimentation rate >20 mm, C-reactive protein positive, segmented nuclear neutrophils and bands greater than 70% in peripheral blood smear, and leukocytosis more than 8,000.
4. Excellent response to treatment with systemic corticosteroids or potassium iodide.
Diagnostic criteria for drug-induced SS include the first three major criteria listed above, in addition to a temporal relationship between drug ingestion/challenge and development or recurrence of the syndrome, as well as symptom resolution after drug withdrawal or corticosteroid administration.2
DIFFERENTIAL DIAGNOSIS
Behçet’s disease is a chronic multisystem disease characterized by ulcerations in the mouth and genitalia, iritis, uveitis, arthritis and thrombophlebitis. HLA B51 is frequently found in patients with Behçet’s disease while HLA B54 is more frequent with SS and rare in Behçet’s disease.13 Corticosteroid therapy may aggravate symptoms in Behçet’s disease, while improving those in SS.13 Drug eruptions have also been implicated in the causation of SS, including the selective cyclo-oxygenase-2 (COX-2) inhibitor celecoxib (Celebrex) and granulocyte colony-stimulating factor.14,15 Both erythema nodosum and SS may occur as reactions to an antecedent viral or bacterial illnesses. The anterior legs are an uncommon site for SS, but it is not unusual for both disease processes to occur concurrently in the same individual. Pyoderma gangrenosum usually begins as a soft nodule on the skin which proceeds to ulcerate. Lesions may follow mild trauma, ulcerations may extend rapidly within a few days and new lesions may appear as older ones resolve.16 Pyoderma gangrenosum is usually responsive to corticosteroids. The differential diagnosis of SS also includes other severe inflammatory and infectious disorders, bowel bypass-related dermatosis, vasculitis, cellulitis, and neoplastic processes (leukemia cutis, lymphoma and metastatic tumor).17,18
MANAGEMENT and TREATMENT
Systemic corticosteroids have been the treatment of choice in most large series of patients reported.8 In most cases, prednisone is extremely and rapidly effective, in doses ranging from 40 mg to 80 mg per day. However, despite the initial excellent response, recurrences of neutrophilic dermatosis are common in 25% of cases and generally develop as steroids are being tapered.19 Topical and intralesional corticosteroids have also been used along with systemic corticosteroids. Occasionally, they are used alone. For long-term management, non-steroidal anti-inflammatory agents such as indomethacin are used as an alternative to corticosteroids. Indomethacin at 150 mg/day for 1 week and 100 mg/day for 2 weeks may alleviate symptoms such as fever and arthralgia within 48 hours and skin lesions within 1 to 2 weeks. Potassium Iodide may also be as effective as corticosteroids.9,11 Colchicine has also been shown effective in a few case reports. However, others found it to be ineffective.8 Dapsone at 100 mg to 200 mg per day has been demonstrated in a few cases as an effective agent in SS, its mechanism being inhibition of bacterial growth and interference with neutrophil infiltration and adherence.8 Cyclosporine, etretinate, doxycycline, clofazamine, pentoxifylline, and the TNF-alpha inhibitor infliximab have also been used with success.2
PROGNOSIS
Since SS may be associated with many other disease processes, prognosis depends on the specific underlying cause, and relapse may occur in up to 50% of patients.6 Recurrence has been reported to most likely occur in conjunction with infections; hematopoietic, lymphoid, and plasma cell disorders; malignant diseases, and various other systemic conditions.20 Hence, it is important to recognize and treat any associated or underlying systemic diseases or malignancies, as SS can serve as a clue to their diagnoses. Most cases of acute neutrophilic dermatosis resolve, although some may persist indefinitely and can be very difficult to manage because of pain and skin breakdown.6 The duration of the lesions in SS original series ranged from 6 weeks to 6 months. This syndrome responds to systemic steroids within few days.8 Untreated, it is seen that most cases will undergo spontaneous remission within 6 to 8 weeks, but rapid spontaneous remission within 2 weeks may also be seen. Some lesions resolve without scarring, although pigmentary changes may take months to resolve. Sweet’s can occur during pregnancy and recur in subsequent pregnancies. Presently, it is believed that the disease is not a threat to the fetus.
