Systemic Lupus Erythematosus–associated Neutrophilic Dermatosis: A Review and Update Allison R. Larson, MD, and Scott R. Granter, MD Abstract: Neutrophilic dermatoses are a rare manifestation of systemic lupus erythematosus (SLE). In recent years, a growing body of literature describes a pathologic spectrum of neutrophilic infiltrates that may be seen in lupus patients. It is particularly important to recognize that neutrophilic dermatoses can be the initial manifestation of SLE in a third of patients. We were able to identify 47 patients with SLE associated with neutrophilic tissue reactions. In this review, we describe the histologic and clinical features of these cases in the hope that increased awareness of this unusual manifestation of SLE will generate prompt diagnosis and improved patient care. Key Words: lupus, neutrophils, bullous lupus, Sweet syndrome (Adv Anat Pathol 2014;21:248–253) BACKGROUND Neutrophilic infiltrates of skin in the setting of lupus patients with bullous systemic lupus erythematosus (SLE) and leukocytoclastic vasculitis are well documented. 1 However, most dermatopathology texts do not consider cutaneous involvement by SLE in the histologic differential diagnosis of neutrophilic inflammatory dermatoses in nonbullous or nonvasculitic lesions. Nevertheless, there is a growing body of literature documenting cell-rich Sweet- like neutrophilic reactions as well as a small number of patients with skin lesions characterized by paucicellular neutrophilic dermal infiltrates. We and others have encountered some patients with moderately cellular neu- trophilic infiltrates in the setting of SLE that bridge the gap between these extremes, providing evidence that there is a spectrum of neutrophilic dermatoses that may be seen in SLE patients. CLINICAL FINDINGS We identified 47 lupus patients with neutrophilic der- matoses in the literature (Table 1). 2–16 Forty-one patients (87%) were female, ranging in age from newborn infants to 67 years old (mean age, 36.96 y). Six patients (13%) were male. A neutrophilic dermatosis was a presenting symptom in 15 patients (32%). In most patients the lesions were violaceous, pink, or erythematous in color, and were most commonly described as papules and plaques. The extrem- ities were involved in 83% of patients, trunk in 60%, and the face or head and neck region in 23% of patients. In addition to patients with SLE, patients with hydralazine- induced lupus and neonatal lupus may also develop or present with neutrophilic dermatoses. 17–20 We were able to identify 4 patients with hydralazine-induced lupus who developed Sweet-like tissue reactions as a presenting symptom (Table 2). The lesions, like those associated with SLE, were described as papules or plaques and involved the face or head and neck area in all 4 patients, the extremities in 2 patients, and the trunk in 1 patient. Of note, 3 of the 4 patients were male and only 1 was female. Three cases of neonatal lupus were identified and included 2 females and 1 male (Table 3). 21,22 The lesions were a presenting clinical feature in all 3 patients. In keeping with SLE-associated neutrophilic tissue reactions, the lesions were described as erythematous and macules, papules, or plaques. HISTOPATHOLOGIC SPECTRUM The lesions show a spectrum range from paucicellular neutrophilic infiltrates in 12 patients (26%) often limited to the papillary dermis, to cell-rich Sweet-like neutrophilic tissue reactions in 24 (52%) patients. Ten patients (22%) fell somewhere in the middle of this spectrum with mod- erately cellular infiltrates (Table 1 and Fig. 1). In patients for whom detailed pathologic descriptions were available, interface changes were seen in 22 patients and dermal mucin was seen in 7. Basement membrane thickening was seen in only 1 patient. Follicular plugging was documented in 1 patient. One case in our series showed a minute discrete focus resembling neutrophilic and gran- ulomatous dermatitis in a background of an otherwise typical neutrophilic dermatosis. Immunofluorescence testing was performed in 14 patients, and immunoreactants at the dermal epidermal junction were seen in the biopsies from 7 patients (50%). CONCLUSIONS In 1972, Fryha et al 23 reported the case of a 37-year- old woman with glomerular renal disease, butterfly rash, and a cutaneous neutrophilic infiltrate consistent with Sweet syndrome. Because the patient did not have anti- nuclear antibodies at the time, she did not meet strict cri- teria for a diagnosis of SLE at that time. In addition, the authors also argue that the biopsy showing Sweet syndrome did not support a diagnosis of SLE—in fact, they posit the histologic findings argued against it. Of course, if the patient did indeed have SLE, the authors would have no way of knowing of an association with neutrophilic tissue reactions as this would be the first case documented. We believe in retrospect that this patient likely represents the From the Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston MA. The authors have no funding or conflicts of interest to disclose. Reprints: Scott R. Granter, MD, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St. J-820, Jimmy Fund Building, Boston, MA 02115 (e-mail: sgranter@partners.org). Copyright r 2014 by Lippincott Williams & Wilkins REVIEW ARTICLE 248 | www.anatomicpathology.com Adv Anat Pathol  Volume 21, Number 4, July 2014