Recurrent Painful Skin Nodules in a 69-Year-Old Woman

Akira Nishizawa, M.D.

Case Report

A 69-year-old female presented with red round lesions on the back of the right hand near the metacarpal joints of the second, third, and fifth fingers one week after onset of upper respiratory infection symptoms. The lesions were slightly raised, circular, mildly tender and well demarcated with an erythematous base. Some areas of the lesions appeared pustular or infected, however, an I&D resulted in no pustular drainage but some serosanguinous drainage which was culture negative.

Initially the lesions were treated with oral cephalosporins, but three days later, the lesions increased in size and appeared even more characteristic of a pustule. She was then hospitalized for IV antibiotics consisting of oxacillin, penicillin, and a short course of gentamicin. The lesions required some minor debridement. About six days later, she was sent home on cephalosporin and penicillin and did well.

Approximately four months later, she had a recurrence of similar lesions on her right hand and again treatment with antibiotics was provided, but the lesions became more extensive and pustular and she was again admitted for IV antibiotic therapy. The lesions were similar in that they were red, raised, pustular, and mildly tender. On this occasion, she had no preceding infection. She was treated with dicloxacillin and ciprofloxacin. A surgeon was consulted for debridement, however, he felt that these lesions did not appear to be infectious and recommended a dermatology consultation. The dermatologist thought that the patient had acute febrile neutrophilic dermatosis (Sweet's syndrome) and performed a skin biopsy which showed changes consistent with a neutrophilic dermatosis. Cultures were again negative for regular, anaerobic, and acid-fast organism. She was treated with steroids (prednisone) in high dosage and responded nicely. Within a day or two, she felt a sense of well being, and two weeks later, the lesions were practically all resolved leaving a slight scar but no discoloration. However, the joint pains were only partially relieved. At this time, six months later, the patient continues to do well without any relapse.

Past history was remarkable for two prior hospitalizations 4 years ago for skin infections that resolved after one month of parenteral antibiotic therapy. She also had long-standing hypertension and arthritis. There was no family history of any unusual skin lesions.

Discussion

R.P. Sweet first described the characteristics ofSweet's syndrome in 1964. In his report, he discussed eight cases of acute febrile neutrophilic dermatosis, all characterized by four cardinal features: fever, peripheral leukocytosis, tender red plaques on the limbs, face and neck, and a dense dermal infiltrate of mature neutrophils. The lesions, which are well demarcated, sometimes become ulcerated and pustular and may form large coalescent lesions.¹

More than five hundred cases have been documented in the literature showing considerable variability in the fever and leukocytosis. Many have reported extracutaneous manifestations and chronic forms. Hence, Sweet's syndrome has become the preferable terminology to describe acute febrile neutrophilic dermatosis. Further, Sweet's syndrome has been classified as one of the neutrophilic dermatoses characterized by cutaneous lesions associated with underlying disease with dense neutrophilic infiltrate of the dermis and usually respond to steroid therapy rather than antibiotics.^1,2

The exact cause of Sweet's syndrome is not known. Some believe that a hypersensitivity reaction leading to the stimulation of a cascade of cytokines that causes neutrophil activation and infiltration may occur. Others feel that T-cell activation is responsible. Finally, HLA analysis in Japanese patients has revealed an increased incidence of HLA Bw 54 but has not been confirmed in European studies.^3,4 Interestingly, spontaneous healing of the skin lesions may occur in two or three weeks. Therefore the so called "Staph infection" may not have necessarily responded to the antibiotics, but may have healed spontaneously.⁵

The mean age at diagnosis is 52.6 years, and the range extends from the fourth decade to the seventh decade. There appears to be female predominance of

3.7 to 1 over males while, in the younger age group,the incidence is about one to one. It has been described in children as well. There seems to be seasonal distribution with peak incidences in the spring and autumn.⁴

Body temperature ranges from subnormal to frank fever, but fever may be intermittent especially in the long-lasting untreated forms. Associated clinical findings include oral mucosal lesions, conjunctivitis, and episcleritis. Arthritis and arthralgia may occur in 32%-62% of cases that usually subside as the cutaneous lesions resolve. The joint pain is characterized by a sero-negative polyarthritis which can involve the hands, wrists, ankles, knees and shoulders, as in the index case. Also, neutrophilic accumulation may occur in sterile extracutaneous sites such as the lungs, bones, and CNS. Genital lesions, while rare, may be seen and thus Behçet's syndrome has to be ruled out. Some lesions of the lower extremities resembling erythema nodosum may occur quite commonly in Sweet's syndrome.⁴

In 1994, von den Driesch subdivided 174 patients from seven different series into four categories: classic/idiopathic 71%, parainflammatory 16%, para-neoplastic 11%, and pregnancy 2%.⁴ Other series have noted the paraneoplastic group to be as high as 33%-54%.⁶

Parainflammatory groups include Crohn's disease, chronic rheumatoid arthritis, ulcerative colitis, Hashimoto's thyroiditis, Sjögren's syndrome, yersiniosis, cholecystitis, pyelonephritis, tonsillitis, URI, UTI, salmonelosis, and others. Paraneoplastic disorders include mostly hematological diseases such as non-Hodgkin's lymphoma, acute leukemia, myelodysplastic syndrome, chronic leukemia, and myeloproliferative disorder as well as solid tumors such as genitourinary cancers, breast cancers, stomach cancers, prostate cancers, lung cancers, and others. Pregnancy contributed to 2% of cases usually occurring in the first and second trimester clearing spontaneously with no fetal morbidity or fatality.⁴

Sweet's syndrome has also been associated with drug sensitivity such as minocycline, TMP-SMX, lithium, furosemide, hydralazine, oral contraceptives, G-CSF, and all trans retinoic acids. In general, Sweet's syndrome associated with malignancy developed severe skin lesions and required aggressive treatment. Treatment of the underlying disease is helpful in resolving the cutaneous lesion. Sweet's syndrome may also precede clinical onset of a malignancy by one year, therefore age-appropriate evaluation for a malignancy should be made.³

To establish a diagnosis is problematic since not all cutaneous lesions are due to allergy or infection but may be a reflection of some underlying systemic disorder. Skin lesions that appear infectious in origin but remain culture negative may be caused by neutrophilic dermatoses such as Sweet's syndrome.

The mainstay in the diagnosis of Sweet's syndrome is the presence of a characteristic lesion described as a mildly tender, erythematus or violacious plaque or nodule. It may appear edematous, pustular, or even ulcerated if advanced. The lesion is culture negative and accompanied by histological findings of a dense neutrophilic band-like papillary dermal infiltrate without leukocytoclastic vasculitis.⁵ In order to help facilitate the diagnosis of Sweet's syndrome, Su and Liu proposed a set of criteria consisting of two major and four minor requiring two major and two out of four minor criteria to establish a diagnosis.⁷ This criteria was further modified by von den Driesch.⁴(Table 1)

Laboratory studies is helpful only if leukocytosis is present but a normal CBC does not exclude Sweet's syndrome. Approximately 80% of the patients have WBC over 8,000 and 60% have WBC over 10,000. Increased leukocytes are less common in drug related Sweet's syndrome. Anemia, present in 67% of cases, is associated with malignancy. Abnormal platelets, such as thrombocytopenia and thrombocytosis, are associated with malignancy. ESR is elevated in 79% of the cases. Approximately 46% of patients have elevated alkaline phosphate levels. And C-reactive protein is elevated in most cases.^3,4

Differential diagnosis includes erythema multi-forme, bowel bypass-related dermatosis, dissemi-

nated erythema nodosum, cellulitis/erysipelas, erythema elevatum diutinum, leukocytoclastic vasculitis, pyoderma gangrenosum, Behçet's syndrome, and chronic neutrophilic plaques.^3,4,5

The first line of treatment for Sweet's syndrome is steroids: prednisone or prednisolone at 0.5-1 mg/kg over two to four weeks with gradual tapering while evaluating clinical response to prevent relapse. A rapid decline in the fever, malaise, oral mucosal lesion, and arthralgia may occur in as early as two days, and cutaneous lesions may show significant improvement over seven days.^4,5

Alternate treatment consists of potassium iodide, dapsone, colchicine, doxycycline, NSAID, clofazamine, and cycloserine. Potassium iodide is felt to be as efficacious as steroids but two cases of severe vasculitis have been described, so caution must be exercised.^4,5 Remember that recurrences are common such as in our index case.

Conclusion

A case of a 69-year-old female with long-standing arthritis with Sweet's syndrome is presented. Initially, confusion regarding the diagnosis of the cutaneous lesion delayed the diagnosis of Sweet's syndrome. A skin biopsy as well as the favorable response to steroid therapy established the diagnosis.

The hallmark of establishing the diagnosis of Sweet's syndrome is the characteristic skin lesion plus the histologic findings of a dense neutrophilic infiltrate of the dermis placing it in the spectrum of similar disorders known as the neutrophilic dermatoses.