- Email: [email protected]
Pulmonary Involvement in Sweet's Syndrome (Acute Febrile Neutrophilic Dermatosis)
botic endocarditis in a Japanese autopsy sample: A review of 80 cases. Am Heart J 1975; 90:190-98 10 Rosen P, Armstrong D. Nonbacterial thrombotic endocarditis in patients with malignant neoplastic diseases. Am J Med 1973;
54:23-9 11 Patchell RA, White CL Ill, Clark AW, Beschorner WE, Santos GW. Neurologic complications of bone marrow transplantation. Neurology 1985; 35:300-06 12 Wooley CF, BabaN, Ryan JM. Nonbacterialthromboticendocarditis. Arch Intern Med 1970; 125:126-28 13 Kooiker JC, Maclean JM, Sumi SM. Cerebral embolism, maran· tic endocarditis and cancer. Arch Neurol 1976; 33:260-64 14 Estevez CM, Corya BC. Serial echocardiographic abnormalities in nonbecterial thrombotic endocarditis of the mitral valve. Chest l976; 69:801-04 15 Fayemi OA. Nonbacterial thrombotic endocarditis and m~ dial in&rction. Am Heart J 1976; 97:40.5-06
Pulmonary Involvement In Sweet's Syndrome (Acute Febrile Neutrophlllc Dermatosls)* and Leukemic Phases of Acµte Myelogenous Leukemia ~kemlc
Angellne A Ltuarw, CDR, MC, F.C.C.P., USN;t Marlon McM"'4n, LCDR, MC, USNR; andArjang M•rtmllJdl, CDR, MC, USN
A 60-year-old man developed bistologic lesions characteristic of acute febrile neutropbilic dermatosis in skin and lung during preleukemic and leukemic phases of acute myeloid leukemia. 'Ibese lesions showed improvement and resolution during oral prednisone therapy, requiring higher doses during each relapse. The response to prednisone therapy was enhanced by concomitant administration of effective antileukemic chemotherapy. Acute febrile neutrophilic dermatosis is an uncommon,
.t1 recurrent, often clnupatic skin disease characterized by painful plaque-forming inflammatory papules. These are associated with fever, arthralgia and peripheral leukocytosis. The typical skin lesions are red to bluish-red papules or nodules. They have a tendency to coalesce and form irreg· ular, sharply bordered plaques. There is pronounced inflammatory edema giving an "illusion of vesciculation." They may occasionally become studded with tiny pustules and central clearing may lead to arcuate or annular patterns. These lesions are painful, tender and enlarge over a period of days to weeks and eventually resolve without scarring. The most common areas of involvement are face, neck, and extensor •From the Departments of Medicine and Pathology, Bethesda Naval Hospital ancfUnlfurmed Services University of Health Sciences, Betliesda. tCurrently Director, Pulmonary Division, Naval Hospital, Portsmouth, Virginia. The opinions ezpressed herein are those of the authors and are not to be construed as reftecting the views ofthe Navy Department, ofthe Naval Service at large, or of the Department of Defense. &print requuta: Cdr Ltuarw, Naval H08J1Ual, Portmwuth, VA 23708
122
FIGURE 1. Chest roentgenogram on 20 Dec 1982 demonstrating right lower lobe infiltrate. No adenopathy or pleural effusion was noted.
aspects of upper extremities. u Over half of these recui; often in previously involved sites. CASE REPORT
This 60-year-old man was well until November 1982, when he developed low-grade fever and malaise. He had normochromic normocytic anemia and thrombocytopenia, and the diagnosis of refractory anemia with excess blasts (RAEB) was made on bone marrow biopsy. He was treated with folate and pyridoxine. One week later, he developed fever and an expanding, ecchymotic, bullous lesion on the dorsum of his right hand. Results of aerobic and anaerobic cultures were negative. The skin lesion progressed during an empiric trial of broad spectrum antibiotics and he was hospi· talized. Chest roentgenogram on admission showed right lower lobe pulmonary infiltrates (Fig 1). Biopsy and culture of the skin lesion and cultures of blood, and sputum were obtained, and antibiotic therapy continued without benefit. The skin biopsy resulted in the diagnosis of"acute febrile neutrophilic dermatosis; also known as "Sweets syndrome" (Fig 2). Antibiotic therapy was discontinued and treabnent with oral prednisone, 60 mg daily, was begun. He became afebrile, and significant improvement of the skin lesion and chest roentgenogram were noted prior to discharge 5 Jan 1983. Over the next two weeks the patient noted recurrent fever and cough while prednisone was being tapered to 20 mg per day. Chest roentgenogram showed recurrence of right lower lobe pulmonary infiltrate, and hemogram demonstrated hemoglobin 6. 9 !Vdl. leuko- . cyte count 21,500/cu mm, and platelet count 21,000lcu mm. He was admitted to the hospital and results ofcultures of blood, sputum, and bronchoscopic washings were negative. The neutrophilic dermatosis of the right hand was healing well at this time. He received tranfusions of red blood cells, broad spectrum antibiotics, and oral prednisone, 100 mg daily. After ten days of therapy, the patient became afebrile, leukocytosis resolved, and improvement in the right lower lobe infiltrate was noted prior to discharge. Prednisone was tapered to 40 mg daily for two weeks, after which he developed recurrent fever to 38.S°C. He was admitted to the hospital and the chest roentgenogram showed progressive bilateral pulmonary infiltrates. On 13 February 1983, a right axillary thoracotomy and open Pulmonary lrwolwmenl In s-ts Syndrome {Lazaru8, McMllan,
Miramadi)
FIGURE 2. Punch biopsy of the skin lesion from the dorsum of the right band demonstrating marked edema of the dermal and papillary dermis, with extensive neutrophilic infiltration. A few eosinophils are also seen. There is no evidence of vasculitis or atypical cellular infiltrate (original magnification x 100).
lung biopsy were perfurmed. The histology of the lung specimen was similar to that of the previous skin biopsy. Prednisone was again increased to 100 mg orally daily, and tapered to 50 mg daily upon discharge one week later. Serial chest roentgenograms over the next month showed resolution of the infiltrate. The patient underwent repeat bone marrow biopsy on 22 March 1983 for persistent transfusion-dependent anemia and thrombocytopenia, and the diagnosis of acute myeloid leukemia (FAB classi&cation M-2) was made. He developed increasing fever and bilateral pulmonary infiltrates on oral prednisone 50 mg daily, and on 2 April 1983 underwent contralateral open lung biopsy. Results of routine bacterial cultures, as well as special stains for acid-fast bacilli, fungi, viral organisms, and Pneumocyaffl cannU were negative. Review of several sections of the lung biopsy specimen showed neutrophilic infiltrates and small areas of fibrosis (Fig 3). Oral prednisone was increased to 100 mg daily fur two weeks, again associated with clinical and roentgenographic improvement, and gradually tapered to 20 mg daily. Antileukemic chemotherapy with cytosine arabinoside, 2 mgim1 twice daily was begun 26 April 1983. In May 1983, purpuric lesions affecting the bands, arms, and groin developed, and biopsy of one of these lesions demonstrated histologic features of neutrophilic dermatosis noted on the initial skin biopsy. Oral prednisone was increased from 30 mg to 120 mg daily with gradual clearing of skin lesions and pulmonary infiltrates. Initial remission was punctuated by recurrent episodes ofleukemic relapse controlled by chemotherapy. Serial chest roentgenograms over the next ten months showed only residual right lower lobe abnormalities. In April, 1984, during a course of chemotherapy, he developed pancytopenia, fever, and new right lower lobe infiltrates. An empiric trial of broad-spectrum antibiotics and high dose prednisone was of no benefit and he expired five days later. Permission fur post-mortem examination was refused.
COMMENTS
FIGURE 3. Section from open lung biopsy ofleft lung demonstrates chronic interstitial pneumonitis, minimal fibrosis and a marked intraalveolar neutrophilic infiltrate. There was no evidence of necrosis or vasculitis (original magni6cation x 100).
In 1964, Sweet' described the features of "acute febrile neutrophilic dermatosis" which has since come to be known as Sweets syndrome. In his original description, the cardinal features included: (a) fever; (b) polymorpbonuclear leukocytosis; (c) raised painful plaques on the extremities, face, and neck; and (d) a dense dermal cellular infiltrate with mature neutropbils on bistology.1.1 The etiology is unknown. There is a history of upper respiratory infection in the majority of patients with this syndrome, suggesting hypersensitivity as a possible pathopbysiologic mechanism. A significant association with hematologic malignancies, particularly acute leukemia, bas been reported, u with manifestations of Sweet's syndrome usually preceding the diagnosis of leukemia. Storer et al8 have shown an association of this syndrome with Sjogrens syndrome, ulcerative colitis, metastatic adenocarcinoma, and testicular carcinoma. Sweet's syndrome bas been noted to occur predominantly in females. No racial predilection bas been noted. It is frequently associated with systemic symptoms of fever, arthralgia, conjunctivitis, and episcleritis. Albuminuria and anemia have also been reported. Matta et al7 reported a case of renal involvement and a case of hepatic involvement, both proven by biopsy. Pulmonary involvement in Sweet's syndrome bas not been reported previously. Our patient bad open lung biopsies from both lungs at different times, and the bistologic changes were similar in both specimens and also similar to those changes noted in skin. Numerous negative culture results, lack of response to CHEST I 90 I 6 I DECEMBER, 1966
923
antibiotics, histolqgy oflung biopsies similar to skin biopsies, and the prompt r,fPOnse to increasing doses of prednisone therapy strongly sqpport the conclusion that this patient had Sweet's syndrome involving skin and lung. Skin and pulmonary changes were both present d1iring the preleukemic (RAEB) phase and flared during neoplastic trailsfurmation to acute myeloid leukemia. Pulmpnary manifestations were active while skin lesions were reiatively quiescent and were more difficult to treat. The effective control of skin and pulmonary manifestations was less difficult while the patient was receiving effective antileukemic chemotherapy. In summary, this patient developed histologic lesions characteristic of acute febrile neutrophillc dermatosis in skin and lung during preleukemic and leukemic phases of acute myeloid leukemia. These lesions showed improvement and resolution during oral prednisone therapy, requiring higher doses during each relapse. The response to prednisone therapy was enhanced by concomitant administration of effective antileukemic chemotherapy.
ACKNOWLEDGMENT: We are indebted to Mrs. Marion Johnson for her secretarial assistance in the preparation of this manuscript REFERENCES
1 Sweet RD. An acute febrile neutrophilic dermatosis. Br J Del'matol 1964; 76:349-56 2 Sweet RD. Acute febrile neutrophilic dermatosis 1-1978. Br J Dermatol 1979; 100:93-99 3 Spector JI, Zimhler H, Levine R, Ross JS, Valigorsky JM, Cole LM. Sweet syndrome-Association with acute leukemia. JAMA 1980; 244:1131-32 4 Gisser SD. Acute febrile neutrophilic dermatosis (Sweets syndrome) in a patient with hairy-cell leukeinia. Am J Dermatopathol 1983; 4:283-88 5 Klock JC, Oken RL. Febrile neutrophilic dermatosis in acute myelogenous leukemia. Cancer 1976; 37:922-27 6 Storer JS, Nesbitt U: Galen WK, Oe Leo VA. Sweets syndrome-a review. lnternat J Dermatol 1983; 22:8-12 7 Matta M, Malak J, 'llabet E, Kurban AK. Sweets syndrome: Systemic Cutis 1973; 12:561-65
association.
54:23-9 11 Patchell RA, White CL Ill, Clark AW, Beschorner WE, Santos GW. Neurologic complications of bone marrow transplantation. Neurology 1985; 35:300-06 12 Wooley CF, BabaN, Ryan JM. Nonbacterialthromboticendocarditis. Arch Intern Med 1970; 125:126-28 13 Kooiker JC, Maclean JM, Sumi SM. Cerebral embolism, maran· tic endocarditis and cancer. Arch Neurol 1976; 33:260-64 14 Estevez CM, Corya BC. Serial echocardiographic abnormalities in nonbecterial thrombotic endocarditis of the mitral valve. Chest l976; 69:801-04 15 Fayemi OA. Nonbacterial thrombotic endocarditis and m~ dial in&rction. Am Heart J 1976; 97:40.5-06
Pulmonary Involvement In Sweet's Syndrome (Acute Febrile Neutrophlllc Dermatosls)* and Leukemic Phases of Acµte Myelogenous Leukemia ~kemlc
Angellne A Ltuarw, CDR, MC, F.C.C.P., USN;t Marlon McM"'4n, LCDR, MC, USNR; andArjang M•rtmllJdl, CDR, MC, USN
A 60-year-old man developed bistologic lesions characteristic of acute febrile neutropbilic dermatosis in skin and lung during preleukemic and leukemic phases of acute myeloid leukemia. 'Ibese lesions showed improvement and resolution during oral prednisone therapy, requiring higher doses during each relapse. The response to prednisone therapy was enhanced by concomitant administration of effective antileukemic chemotherapy. Acute febrile neutrophilic dermatosis is an uncommon,
.t1 recurrent, often clnupatic skin disease characterized by painful plaque-forming inflammatory papules. These are associated with fever, arthralgia and peripheral leukocytosis. The typical skin lesions are red to bluish-red papules or nodules. They have a tendency to coalesce and form irreg· ular, sharply bordered plaques. There is pronounced inflammatory edema giving an "illusion of vesciculation." They may occasionally become studded with tiny pustules and central clearing may lead to arcuate or annular patterns. These lesions are painful, tender and enlarge over a period of days to weeks and eventually resolve without scarring. The most common areas of involvement are face, neck, and extensor •From the Departments of Medicine and Pathology, Bethesda Naval Hospital ancfUnlfurmed Services University of Health Sciences, Betliesda. tCurrently Director, Pulmonary Division, Naval Hospital, Portsmouth, Virginia. The opinions ezpressed herein are those of the authors and are not to be construed as reftecting the views ofthe Navy Department, ofthe Naval Service at large, or of the Department of Defense. &print requuta: Cdr Ltuarw, Naval H08J1Ual, Portmwuth, VA 23708
122
FIGURE 1. Chest roentgenogram on 20 Dec 1982 demonstrating right lower lobe infiltrate. No adenopathy or pleural effusion was noted.
aspects of upper extremities. u Over half of these recui; often in previously involved sites. CASE REPORT
This 60-year-old man was well until November 1982, when he developed low-grade fever and malaise. He had normochromic normocytic anemia and thrombocytopenia, and the diagnosis of refractory anemia with excess blasts (RAEB) was made on bone marrow biopsy. He was treated with folate and pyridoxine. One week later, he developed fever and an expanding, ecchymotic, bullous lesion on the dorsum of his right hand. Results of aerobic and anaerobic cultures were negative. The skin lesion progressed during an empiric trial of broad spectrum antibiotics and he was hospi· talized. Chest roentgenogram on admission showed right lower lobe pulmonary infiltrates (Fig 1). Biopsy and culture of the skin lesion and cultures of blood, and sputum were obtained, and antibiotic therapy continued without benefit. The skin biopsy resulted in the diagnosis of"acute febrile neutrophilic dermatosis; also known as "Sweets syndrome" (Fig 2). Antibiotic therapy was discontinued and treabnent with oral prednisone, 60 mg daily, was begun. He became afebrile, and significant improvement of the skin lesion and chest roentgenogram were noted prior to discharge 5 Jan 1983. Over the next two weeks the patient noted recurrent fever and cough while prednisone was being tapered to 20 mg per day. Chest roentgenogram showed recurrence of right lower lobe pulmonary infiltrate, and hemogram demonstrated hemoglobin 6. 9 !Vdl. leuko- . cyte count 21,500/cu mm, and platelet count 21,000lcu mm. He was admitted to the hospital and results ofcultures of blood, sputum, and bronchoscopic washings were negative. The neutrophilic dermatosis of the right hand was healing well at this time. He received tranfusions of red blood cells, broad spectrum antibiotics, and oral prednisone, 100 mg daily. After ten days of therapy, the patient became afebrile, leukocytosis resolved, and improvement in the right lower lobe infiltrate was noted prior to discharge. Prednisone was tapered to 40 mg daily for two weeks, after which he developed recurrent fever to 38.S°C. He was admitted to the hospital and the chest roentgenogram showed progressive bilateral pulmonary infiltrates. On 13 February 1983, a right axillary thoracotomy and open Pulmonary lrwolwmenl In s-ts Syndrome {Lazaru8, McMllan,
Miramadi)
FIGURE 2. Punch biopsy of the skin lesion from the dorsum of the right band demonstrating marked edema of the dermal and papillary dermis, with extensive neutrophilic infiltration. A few eosinophils are also seen. There is no evidence of vasculitis or atypical cellular infiltrate (original magnification x 100).
lung biopsy were perfurmed. The histology of the lung specimen was similar to that of the previous skin biopsy. Prednisone was again increased to 100 mg orally daily, and tapered to 50 mg daily upon discharge one week later. Serial chest roentgenograms over the next month showed resolution of the infiltrate. The patient underwent repeat bone marrow biopsy on 22 March 1983 for persistent transfusion-dependent anemia and thrombocytopenia, and the diagnosis of acute myeloid leukemia (FAB classi&cation M-2) was made. He developed increasing fever and bilateral pulmonary infiltrates on oral prednisone 50 mg daily, and on 2 April 1983 underwent contralateral open lung biopsy. Results of routine bacterial cultures, as well as special stains for acid-fast bacilli, fungi, viral organisms, and Pneumocyaffl cannU were negative. Review of several sections of the lung biopsy specimen showed neutrophilic infiltrates and small areas of fibrosis (Fig 3). Oral prednisone was increased to 100 mg daily fur two weeks, again associated with clinical and roentgenographic improvement, and gradually tapered to 20 mg daily. Antileukemic chemotherapy with cytosine arabinoside, 2 mgim1 twice daily was begun 26 April 1983. In May 1983, purpuric lesions affecting the bands, arms, and groin developed, and biopsy of one of these lesions demonstrated histologic features of neutrophilic dermatosis noted on the initial skin biopsy. Oral prednisone was increased from 30 mg to 120 mg daily with gradual clearing of skin lesions and pulmonary infiltrates. Initial remission was punctuated by recurrent episodes ofleukemic relapse controlled by chemotherapy. Serial chest roentgenograms over the next ten months showed only residual right lower lobe abnormalities. In April, 1984, during a course of chemotherapy, he developed pancytopenia, fever, and new right lower lobe infiltrates. An empiric trial of broad-spectrum antibiotics and high dose prednisone was of no benefit and he expired five days later. Permission fur post-mortem examination was refused.
COMMENTS
FIGURE 3. Section from open lung biopsy ofleft lung demonstrates chronic interstitial pneumonitis, minimal fibrosis and a marked intraalveolar neutrophilic infiltrate. There was no evidence of necrosis or vasculitis (original magni6cation x 100).
In 1964, Sweet' described the features of "acute febrile neutrophilic dermatosis" which has since come to be known as Sweets syndrome. In his original description, the cardinal features included: (a) fever; (b) polymorpbonuclear leukocytosis; (c) raised painful plaques on the extremities, face, and neck; and (d) a dense dermal cellular infiltrate with mature neutropbils on bistology.1.1 The etiology is unknown. There is a history of upper respiratory infection in the majority of patients with this syndrome, suggesting hypersensitivity as a possible pathopbysiologic mechanism. A significant association with hematologic malignancies, particularly acute leukemia, bas been reported, u with manifestations of Sweet's syndrome usually preceding the diagnosis of leukemia. Storer et al8 have shown an association of this syndrome with Sjogrens syndrome, ulcerative colitis, metastatic adenocarcinoma, and testicular carcinoma. Sweet's syndrome bas been noted to occur predominantly in females. No racial predilection bas been noted. It is frequently associated with systemic symptoms of fever, arthralgia, conjunctivitis, and episcleritis. Albuminuria and anemia have also been reported. Matta et al7 reported a case of renal involvement and a case of hepatic involvement, both proven by biopsy. Pulmonary involvement in Sweet's syndrome bas not been reported previously. Our patient bad open lung biopsies from both lungs at different times, and the bistologic changes were similar in both specimens and also similar to those changes noted in skin. Numerous negative culture results, lack of response to CHEST I 90 I 6 I DECEMBER, 1966
923
antibiotics, histolqgy oflung biopsies similar to skin biopsies, and the prompt r,fPOnse to increasing doses of prednisone therapy strongly sqpport the conclusion that this patient had Sweet's syndrome involving skin and lung. Skin and pulmonary changes were both present d1iring the preleukemic (RAEB) phase and flared during neoplastic trailsfurmation to acute myeloid leukemia. Pulmpnary manifestations were active while skin lesions were reiatively quiescent and were more difficult to treat. The effective control of skin and pulmonary manifestations was less difficult while the patient was receiving effective antileukemic chemotherapy. In summary, this patient developed histologic lesions characteristic of acute febrile neutrophillc dermatosis in skin and lung during preleukemic and leukemic phases of acute myeloid leukemia. These lesions showed improvement and resolution during oral prednisone therapy, requiring higher doses during each relapse. The response to prednisone therapy was enhanced by concomitant administration of effective antileukemic chemotherapy.
ACKNOWLEDGMENT: We are indebted to Mrs. Marion Johnson for her secretarial assistance in the preparation of this manuscript REFERENCES
1 Sweet RD. An acute febrile neutrophilic dermatosis. Br J Del'matol 1964; 76:349-56 2 Sweet RD. Acute febrile neutrophilic dermatosis 1-1978. Br J Dermatol 1979; 100:93-99 3 Spector JI, Zimhler H, Levine R, Ross JS, Valigorsky JM, Cole LM. Sweet syndrome-Association with acute leukemia. JAMA 1980; 244:1131-32 4 Gisser SD. Acute febrile neutrophilic dermatosis (Sweets syndrome) in a patient with hairy-cell leukeinia. Am J Dermatopathol 1983; 4:283-88 5 Klock JC, Oken RL. Febrile neutrophilic dermatosis in acute myelogenous leukemia. Cancer 1976; 37:922-27 6 Storer JS, Nesbitt U: Galen WK, Oe Leo VA. Sweets syndrome-a review. lnternat J Dermatol 1983; 22:8-12 7 Matta M, Malak J, 'llabet E, Kurban AK. Sweets syndrome: Systemic Cutis 1973; 12:561-65
association.