Objectives  To describe the clinical and histopathologic characteristics of this rare disorder; to compare and contrast these features with those of Sweet syndrome; and to investigate possible associations with systemic diseases.

Observations  Seven women were referred for pustular or ulcerative plaques and nodules on the dorsal hands. In most patients, the initial diagnosis was cutaneous infection, but antibiotic therapy was ineffective. Skin biopsy specimens showed dense dermal neutrophilic infiltrates with leukocytoclasis and fibrinoid vascular necrosis. Cutaneous cultures yielded negative findings in all cases. Prednisone and dapsone appeared to be helpful, but recurrences were common. Minocycline hydrochloride was of uncertain benefit. Among the 7 patients, possible systemic associations included bowel disorders and a urinary tract infection.

Conclusions  Neutrophilic dermatosis of the dorsal hands may be closely related to Sweet syndrome but frequently shows the histologic pattern of leukocytoclastic vasculitis. Recognition of this disorder is important, because it may be misdiagnosed as a localized cutaneous infection. Additional studies are needed to investigate further the possible associations with internal diseases, especially bowel disorders.

We describe clinical and histopathologic findings in 7 patients with neutrophilic dermatosis or pustular vasculitis of the dorsal hands.

PATIENTS AND METHODS

Follow-up information was obtained during patients' subsequent visits in the department. When needed, additional information was obtained by means of questionnaires, which were sent to the patients or to the physicians who had previously referred the patients.

RESULTS

Clinical and laboratory data are summarized in Table 1. All patients were women, who ranged in age from 44 to 82 years; the mean age was 64 years. Three patients had a history of minor trauma to the hands preceding the eruption. Cutaneous infections were suspected in most of the patients, and they had been treated unsuccessfully with systemic antibiotics before evaluation in our department. All patients presented with severely painful purulent nodules and plaques, frequently accompanied by ulceration, involving predominantly the dorsal hands (Figure 1). Areas of involvement on the dorsal hands variably included the radial aspect, the ulnar aspect, or both. In addition to the hand lesions, other anatomic sites were minimally involved in 5 patients.

View this table: [in this window] [in a new window] Clinical and Laboratory Data

View larger version (100K): [in this window] [in a new window] Figure 1. Ulcerated pustular plaque on the dorsal hand of patient 7.

HISTOPATHOLOGIC, CULTURE, AND DIRECT IMMUNOFLUORESCENCE FINDINGS

Biopsy specimens from hand lesions of all patients showed dense dermal infiltrates of neutrophils (Figure 2 and Figure 3), sometimes associated with subepidermal edema. Abundant leukocytoclastic nuclear dust was present extracellularly and within dermal macrophages. Variable numbers of eosinophils and lymphocytes were also present. Fibrinoid necrosis of small vessels was evident in all cases. Epidermal findings included spongiosis, ulceration, neutrophilic infiltration, and in some cases, neutrophilic microabscesses. Pseudoepitheliomatous hyperplasia was present in 2 cases. No fungi or mycobacteria were seen with the use of special stains. All cultures of cutaneous specimens yielded negative findings.

View larger version (107K): [in this window] [in a new window] Figure 2. Dense dermal infiltrate with intraepidermal pustules in patient 3 (hematoxylin-eosin, original magnification x40).

View larger version (124K): [in this window] [in a new window] Figure 3. Necrotic vessel (oriented longitudinally) surrounded by neutrophils and leukocytoclastic debris in patient 7 (hematoxylin-eosin, original magnification x400).

In patient 2, an additional biopsy was performed on an inconspicuous papule on the back. This specimen showed neutrophilic and histiocytic dermal inflammation consistent with Sweet syndrome. Vascular fibrinoid necrosis was absent in the back lesion, but was evident in the hand specimen.

Direct immunofluorescence, which was performed on the hand specimen from patient 2, revealed no vascular deposits of immunoglobulin, complement, or fibrinogen.

TREATMENT AND CLINICAL COURSE

Follow-up ranged from 1 month to 4 years; median follow-up was 1 year. Cutaneous lesions resolved in 6 of 7 patients, during a period of 1 to 9 weeks. Those 6 patients had been treated with prednisone, dapsone, or minocycline hydrochloride. No hematologic disorder developed in any patient. One patient died of chronic renal failure shortly after the evaluation of her hand lesions.

COMMENT

In 1995, Strutton et al¹ described 6 women with lesions resembling Sweet syndrome, but with a distribution limited almost entirely to the dorsal hands. In contrast to most cases of Sweet syndrome, those 6 cases showed definite leukocytoclastic vasculitis. The term pustular vasculitis of the hands was used to describe this eruption. In all cases, the hands were the predominant site of involvement, although lip ulceration was present in 1 patient. Similar dorsal hand lesions showing fibrinoid vascular necrosis were subsequently reported in 3 patients, including 2 men.^2-3

Galaria et al⁴ recently described 3 additional patients with hand lesions that clinically resembled the previous cases of pustular vasculitis. In their 3 cases, however, dense dermal neutrophilic infiltrates were present without diagnostic features of vasculitis. They therefore proposed that the entity be renamed neutrophilic dermatosis of the dorsal hands and suggested that it was a subset of Sweet syndrome.

Further links to Sweet syndrome were evident in patient 2 of the present series. The biopsy specimen from her hand showed a neutrophilic dermal infiltrate with fibrinoid vascular necrosis, whereas the biopsy specimen from a papule on her back showed a neutrophilic infiltrate without vasculitis. Five of our patients also had lesions at sites other than the hands. These areas of involvement were typically minimal and, in some cases, had not been noticed by the patients. However, the clinical and histopathologic features of the hand lesions were very similar to those described in previous cases of NDDH. Additional features resembling Sweet syndrome in these 7 patients included female sex (7 cases), pathergy (3 cases), fever (3 cases), and peripheral blood neutrophilia (2 cases). At the time of laboratory testing, 1 of the 2 patients with neutrophilia was already receiving treatment with oral prednisone, which may have caused the neutrophilia.

The original description of acute febrile neutrophilic dermatosis noted the association with a preceding upper respiratory tract infection.⁵ Subsequent reports have linked Sweet syndrome to myeloproliferative disorders, myelocytic leukemia, visceral malignancies, inflammatory bowel disease, connective tissue diseases, pregnancy, infections, drug reactions, and other disorders.^{6, 8} Because relatively few reported cases of NDDH exist, the possible systemic associations in these patients are less clear. In previous reports, associations of uncertain significance have included a history of breast carcinoma in 2 patients,¹ preceding pharyngitis,² metastatic renal adenocarcinoma,² and Raynaud disease with arthritis.⁴

Three patients in the present series had concurrent bowel disorders at the onset of their cutaneous lesions. These active problems included diverticulosis, diverticulitis, acute proctitis (with a sigmoidoscopic appearance suggestive of diverticulitis or segmental colitis), a tubulovillous adenoma, and possible diabetic gastropathy. In addition, 1 of the 3 patients had a history of small-bowel obstruction. It is not clear whether these bowel disorders are related to the cutaneous eruption. Another neutrophilic dermatosis, bowel-associated dermatosis-arthritis syndrome, has been reported in patients with previous bowel bypass procedures and other bowel disorders.¹² The syndrome may be related to bacterial antigens and immune complexes that occur in the setting of bacterial overgrowth in the bowel.¹³ In contrast to NDDH, bowel-associated dermatosis-arthritis syndrome typically has a widespread distribution on the upper extremities and trunk.¹² Another neutrophil-rich cutaneous disorder, pyoderma gangrenosum,¹⁴ is commonly associated with inflammatory bowel disease.

In patient 2, an additional possible association included a concurrent urinary tract infection. Resolution of her hand lesions occurred after antibiotic therapy for the urinary tract infection and simultaneous treatment with oral prednisone. Thus, it is difficult to know which action may have contributed to her improvement.

Sweet syndrome may sometimes occur as a drug reaction.¹⁵ In typical cases, the initiation of the medication therapy and the onset of the eruption are closely associated in time. None of the medication therapy described in Table 1 had a clear temporal relationship with eruption in these 7 patients.

Neutrophilic dermatosis of the dorsal hands may respond to treatments that are commonly used for Sweet syndrome. The usefulness of oral corticosteroids^1-4 and dapsone⁴ has been described previously. Minocycline^16-17 may be helpful for pyoderma gangrenosum, but its use has not previously been reported in NDDH. In the present study, both patients who were treated with minocycline initially improved, then experienced subsequent recurrences during minocycline therapy. In addition, minocycline has been reported as a possible cause of drug-induced Sweet syndrome.^18-19

Appropriate treatment of NDDH may be delayed because of misdiagnosis. Six of the 7 patients in the present report were originally believed to have cutaneous infections. Systemic antibiotics were given without benefit. Histologic findings, such as neutrophilic infiltrates and pseudoepitheliomatous hyperplasia, may also mimic infection.

CONCLUSIONS

Corresponding author and reprints: David J. DiCaudo, MD, Mayo Clinic Scottsdale, 13400 E Shea Blvd, Scottsdale, AZ 85259.