Sweet syndrome associated with erythema nodosum: are they different manifestations of the same disease?

To the Editor: Sweet Syndrome (SS, acute febrile neutrophilic dermatosis) is a rarely seen disease that includes abruptly developing painful papullonodular or plaque-shaped erythematous lesions associated with systemic findings such as malaise, fever, arthralgia, conjunctivitis and episcleritis, and histologically characterized by edema on the upper dermis and intense neutrophilic infiltration. SS is a reactive dermatitis which may be an early and associated manifestation of various diseases such as malignancies (especially hematological) but may also occur in healthy humans. Erythema nodosum is usually characterized by abruptly developing, painful, erythematous nodules on the front side of the tibia. It is manifested histologically as septal granulomatous panniculitis. These dermatoses are rarely seen together. (1)

We report a patient who was diagnosed with tuberculosis as well as two simultaneously occurring dermatoses. A 44-year-old female patient was admitted to the hospital with complaints of malaise, fever, pain and redness in her right eye. Past medical history did not reveal any previous disease. Fifteen days before hospitalization, the patient developed red-colored, plaque-shaped, painful lesions on both forearms and red, painful nodular lesions on the front of both tibias.

Her physical examination revealed a blood pressure of 110/70 mm Hg, and a temperature of 39[degrees]C. She had papular, confluent, erythematous and painful nodular lesions on both legs. She did not have any other systemic findings.

Laboratory findings revealed a leukocyte count of 12,400/mL, neutrophils of 9,200/mL, lymphocytes 2,300/mL, erythrocytes 4,000/mL, Hb 12 g/dL, Hct 35%, MCH 84 fl, platelets 645,000/mL, erythrocyte sedimentation rate 127 mm/h, and a CRP of 148 mg/L. Serum biochemical investigations included serum iron of 23 mg/dL (N:50-175) and iron binding capacity of 232 mg/dL (N:250-410), LDH 610 U/L (N:240-480). Other serum biochemical investigations, blood smear, tumor markers (CEA, CA 15-3, Cal25) and urinalysis were normal. There were no pathologic findings on throat, blood, urine or feces cultures. ASO titers were within normal limits (74 IU/mL). A punch biopsy from lesions on the forearms revealed prominent edema on the upper dermis and intense cellular infiltration, and predominantly lymphocytes, polymorphonuclear neutrophils and leucocytoclasis on the perivascular areas. Lesions which were clinically diagnosed as erythema nodosum on both legs were not histopathologically investigated.

Her serologic investigation showed that ANA, ANCA, and anti-ENA screening were negative and her complement 3 level was within normal limits. Lung function tests were normal. Chest radiography showed that there was a prominent solid density on the right hilar side. For this reason, a computed thorax tomography was performed, which showed multiple lymph nodes localized on the subcarinal and paratracheal areas, and a centrally-localized, soft tissue density lesion with irregular borders, causing minimal distortion on the peripheral parenchymal tissue on the superior segment of the lower lobe of the right lung. Biopsies taken from this region by fiberoptic bronchoscopy did not reveal any atypical cells or specific findings. Biopsies taken by extended mediastinoscopy showed a necrotizing granulomatous lymphadenitis. PPD test was positive with a 13-mm induration.

She was diagnosed with tuberculosis and was started on a four-drug regimen of antituberculous therapy. Mycobacterium tubeculosis bacilli grew in Loweinstein media culture. She was discharged from the hospital after her general condition improved and her skin lesions receded.

SS usually occurs during streptoccocal and Yersinia infections, although it is rarely seen in lung tuberculosis. SS associated with erythema nodosum is rarely seen.

The pathogenesis of SS includes immune complex diseases and increased neutrophil and cytokine response against superantigens. Histopathological properties of erythema nodosum includes neutrophilic vascular reaction within the dermis and subcutaneous tissue and granulomatous panniculitis. Skin lesions due to tuberculosis have reportedly developed against mycobacterial antigens. (3) The occurrence of SS and erythema nodosum implies that two different reactions developed against one agent and the etiology occured due to bacterial hypersensivity. (4) Similarly, the occurrence of both dermatoses in patients who have undergone intestinal bypass supports the role of bacterial infections in the pathogenesis. In addition, erythema nodosum may also occur during SS. (5) Similarly, the effect of potassium iodide on the therapy of both dermatoses supports the association of the two diseases.

In conclusion, SS and erythema nodosum may manifest during similar diseases and may have similar clinical findings. For this reason, it may imply the same pathogenesis.

Gonenc Kocabay, MD

Department of Internal Medicine

Atahan Cagatay, MD

Asli Karadeniz, MD

Department of Infectious Diseases and Clinical Microbiology

Istanbul School of Medicine

Istanbul University

Istanbul, Turkey

References

1. Singh RK. Acute febrile neutrophilic dermatosis following tuberculous infection. J Assoc Physicians India 2002;50:1322-1323.

2. Waltz KM, Long D, Marks JG Jr, et al. Sweet's syndrome and erythema nodosum: the simultaneous occurrence of 2 reactive dermatoses. Arch Dermatol 1999;135:62-66.

3. Honigsmann H, Cohen PR, Wolff K. Inflammatory and neoplastic disorders of the dermis. In: Freedberg IM, Eisen AT, Wolff KK, et al (eds). Dermatology in General Medicine. 5th ed. New York, McGraw-Hill Co, 1999, pp 1117-1123.

4. Spaz SA. Erythema nodosum in Sweet's syndrome. Cutis 1985;35:327-330.

5. Bondi EE, Margolis DJ, Lazarus GS. Panniculitis. In: Freedberg, IM, Eisen AZ, Wolff K, et al (eds). Dermatology in General Medicine. 5th ed. New York, McGraw-Hill, 1999, pp 1275-1289.