SS usually manifests in adults, ages 50 to 60 years, but may rarely occur in the pediatric population. Some reports suggest a female predominance, although other studies fail to confirm this.³ In fact, the male-to-female ratio is equal in the pediatric population and in patients with malignancies.⁴

Six main types of SS are known: classic/idiopathic, autoimmune disease–associated, postinfectious, malignancy-associated (MA-SS), pregnancy-associated (PA-SS), and drug-associated (DA-SS). Autoimmune-associated disorders include systemic lupus erythematosus, dermatomyositis, Hashimoto thyroiditis, Crohn disease, ulcerative colitis, Behçet disease, pemphigus vulgaris, rheumatoid arthritis, and Sjögren syndrome.³ Infections have been documented in about 25% of SS cases.³ Respiratory viral infections are more common, except for the pediatric population prior to 2 months of life, when bacterial infections predominate.⁴ Other associated infections include tuberculosis, parvovirus B19, sporotrichosis, tularemia, hepatitis B and C.^5,6,7

MA-SS comprises 30% of patients with SS.⁸ SS lesions may herald the initial onset of the malignancy or may precede the cancer diagnosis for many years. SS may be a sign of recurrence, but chemotherapy-induced SS should be excluded. Hematologic malignancies represent 85% of all MA-SS cases, with acute myelogenous leukemia (AML) being the most common. SS is seen in about 1% of patients with AML either before or after the diagnosis is made.⁹ In over 50% of patients with AML-associated SS, myelodysplastic syndrome (MDS) precedes AML; complex cytogenetics (mutations in -5/del(5q) and FLT3) and therapy-related AML are among the other AML associations.⁹ Other hematologic disorders, such as chronic myelogenous leukemia (CML), essential thrombocytemia, and polycythemia vera (PV); paraproteinemias (multiple myeloma [MM] and monoclonal gammopathy of undetermined significance [MGUS]); chronic lymphocytic leukemia (CLL), some anemias (Fanconi anemia, aplastic anemia, and other refractory anemias), hairy cell leukemia, Hodgkin disease, and diffuse large B-cell lymphoma, are less frequent.^{10,11,12,13,14} SS in patients with Fanconi anemia and PV may indicate progression of the disease with evolution to MDS and AML.^15,16 Solid tumors associated with SS include genitourinary malignancies (ovarian, bladder, prostate, cervical cancers), breast carcinoma, and less frequently, papillary thyroid carcinoma and lung cancer.⁷

PA-SS comprises less than 2% of SS cases. It may appear in any stage of pregnancy, and often recurs during the same or subsequent pregnancies.¹⁷ A normal delivery is expected, although early miscarriage may rarely occur in fulminant SS.^18,19,20

A diagnosis of DA-SS requires fulfilling appropriate SS criteria plus a temporal relationship between drug intake and eruption.²¹ Multiple drugs may cause SS, with granulocyte colony-stimulating factor (G-CSF), vaccines (smallpox, BCG, influenza, and pneumococcal), and all-trans-retinoid acid (ATRA) being most common.²² Other miscellaneous drugs that were reported to cause SS include antivirals (acyclovir, abacavir), antibiotics (trimethoprim–sulfasalazine, minocycline), imatinib, bortezomib, hydralazine, furosemide, azathioprine, celecoxib, clonazepam, lorazepam, diazepam, amoxapine, and oral contraceptives.

The incidence of idiopathic SS is ∼11%; however, as this group often includes parainflammatory and postinfectious cases, the true incidence of idiopathic SS is not known. Longer follow-up may be needed to reveal an underlying condition.²³

The pathogenesis of SS is unknown. Observations that may have etiologic implications include the findings of elevated levels of G-CSF in patients with active SS (compared with inactive disease), interleukin-1 (IL-1), IL-2, and interferon-γ stimulation of G-CSF production by macrophages and decreased apoptosis of neutrophils in women, aggravated by progesterone.^24,25,26

Clinically, SS lesions have a predilection for the head, extremities (upper > lower), and dorsal hands, but may occur anywhere.⁷ Photodistribution may occur (Fig. 58-1). Oral, ocular, and/or genital mucosal involvement is not common, but may occur, especially in MA-SS, in which widespread involvement is frequent.²⁷ Morphologically, SS lesions are tender erythematous–violaceous papules, nodules, or plaques (Fig. 58-1B–E). Less commonly, the lesions may be targetoid or figurate (Fig. 58-1F), pseudovesicular, or bullous, or may mimic panniculitis (Fig. 58-1G), which clinically is nearly identical to erythema nodosum if on the lower extremities. SS may also mimic cellulitis and necrotizing fasciitis.²⁸ The subtype of SS, termed “neutrophilic dermatosis of the dorsal hands (NDDH),” is usually localized to the area of dorsal hands and fingers, where it presents as tender hemorrhagic, bullous, ulcerated, pseudopustular, or pseudovesicular plaques (Fig. 58-1H), and is frequently biopsied with a suspicion of infection.²⁹