We report a case of adult staphylococcal scalded skin syndrome (SSSS) superimposed on acute graft-vs-host disease (GVHD) and discuss the unique histologic features of both conditions seen on skin biopsy.
A man in his 60s with a history of myelodysplastic syndrome underwent a matched unrelated donor hematopoietic stem cell transplant (HSCT) after conditioning with fludarabine and total-body irradiation. Prophylaxis against GVHD included cyclosporine A, 175 mg, and mycophenolate mofetil, 1000 mg, both given orally twice daily. On day 35 after HSCT, the patient developed nontender erythematous macules and papules on the thighs, which subsequently spread to the trunk and extremities. The patient later developed diarrhea and mildly elevated serum total bilirubin levels (1.5 mg/dL). Skin and colon biopsies confirmed acute GVHD, and the patient was treated with intravenous methylprednisolone, 200 mg/d, with resolution of symptoms.
On day 144 after HSCT, the patient developed diarrhea and mildly tender diffusely scattered erythematous macules and papules on the trunk, neck, face, and extremities, along with acute kidney injury (creatinine, 2.94 mg/dL). Owing to a recent fever, the patient began treatment with intravenous linezolid, 600 mg, twice daily and intravenous cefepime, 2 g/d. Treatment with intravenous methylprednisolone, 100 mg/d, was also started for suspected recurrent acute GVHD. On day 146, the skin lesions progressed to diffuse erythroderma with large areas of superficial desquamation, most notable on the proximal, flexural regions of the arms and thighs (Figure 1).
Erythroderma with large areas of superficial desquamation, most notable in intertriginous and flexural regions.
Skin biopsy from the right thigh revealed superficial interface dermatitis, prominent vacuolar degeneration of the basal layer, and satellite cell necrosis with superimposed subcorneal splitting and acantholysis (Figure 2). A diagnosis of GVHD with coexisting SSSS was made based on the clinical findings and histopathologic changes. Blood cultures remained negative, and the diarrhea and desquamative changes improved under treatment with systemic steroids and intravenous vancomycin. The patient’s condition deteriorated secondary to a pulmonary embolism and pneumonia, and intubation was required. After discussions with the patient’s family, medical treatment was discontinued. Respiratory support was removed, and the patient died on day 154.
Epidermal keratinocytes undergoing apoptosis secondary to graft-vs-host disease with superimposed subcorneal layer separation and acantholysis (hematoxylin-eosin, original magnification ×400).
Acute GVHD involving the skin can range from patchy erythema to erythroderma with diffuse desquamation. Clinical differentiation of severe acute GVHD from other desquamative eruptions, including SSSS, is difficult because they have similar physical findings. Although SSSS is more common in children, renal impairment and Staphylococcus aureus burden caused by immunosuppression are major predisposing factors for SSSS in adults.1 In these patients, early diagnosis and management of SSSS is critical because treatment with corticosteroids for presumed GVHD may worsen SSSS, and mortality can be as high as 54%.2,3 Clinically, both SSSS and acute GVHD manifest as desquamative dermatoses, though the desquamation seen in SSSS is an immediate phenomenon, and desquamation in acute GVHD typically follows the erythematous or morbilliform component that heralds the disease.
Accurate differentiation of acute GVHD from SSSS requires histologic examination. Whereas GVHD demonstrates vacuolar degeneration of the basal layer and satellite cell necrosis, SSSS is characterized by acantholysis and intraepidermal splitting. Rapid diagnosis of SSSS may also be achieved with frozen-sectioning of a skin biopsy specimen demonstrating granular layer cleavage.4 Given our patient’s medication regimen, drug hypersensitivity reactions were also considered. However, the facial and palmar involvement, history of diarrhea, and skin biopsy findings strongly suggested acute GVHD and coexisting SSSS.5
Although 1 other case of SSSS in a patient with a history of cutaneous GVHD exists,6 to our knowledge, ours is the first reported case of acute GVHD and coexistent SSSS. Despite the clinical similarities, the 2 conditions have unique histologic features, and skin biopsy should be performed in HSCT patients to delineate the diagnosis when appropriate.
Corresponding Author: Jonathan A. Cotliar, MD, Robert H. Lurie Comprehensive Cancer Center, Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N St Clair St, Ste 1600, Chicago, IL 60611 (firstname.lastname@example.org).
Published Online: October 22, 2014. doi:10.1001/jamadermatol.2014.2546.
Conflict of Interest Disclosures: None reported.
Thomas C, Yazdan P, Cotliar JA. Coexistence of Staphylococcal Scalded Skin Syndrome and Acute Graft-vs-Host Disease. JAMA Dermatol. 2015;151(3):343-345. doi:10.1001/jamadermatol.2014.2546