Granulocyte colony-stimulating factor as a cause of acute leucocytoclastic vasculitis with anti-Ro and anti-La antibodies

Background

Granulocyte colony-stimulating factor (G-CSF) is a myeloid growth factor that stimulates neutrophil proliferation and is commonly used in patients undergoing chemotherapy for solid and haematological malignancies.1 Serious dermatological side effects of G-CSF include Sweet’s syndrome and exacerbations of pre-existing inflammatory disorders such as psoriasis.2 Acute leucocytoclastic vasculitis (ALV) is an extremely rare complication of G-CSF therapy, having been reported in less than 10 patients receiving G-CSF treatment.3 No previous reports have described an association between ALV and anti-Ro or anti-La antibodies. Here, we describe the first case, to our knowledge, of G-CSF induced ALV associated with anti-Ro and anti-La antibodies. Our case illustrates how patients with skin of colour may have atypical presentations of G-CSF-induced ALV, and therefore, clinicians should have a high index of clinical suspicion in this patient population.

Case presentation

A man in his 50s presented with a 1-day history of rapidly progressive painful ankle swelling and darkening of his ankles and soles. This started 3 days after daily G-CSF injections for management of leucopenia. His leucopenia was secondary to melphalan and bortezomib, cyclophosphamide and dexamethasone chemotherapy with an autograft for IgG kappa multiple myeloma. He denied any other rashes, photosensitivity, oral ulcers, arthralgias, chest pain, shortness of breath, haematuria, dry eyes or dry mouth. A medical history was notable for treated pulmonary sarcoidosis, glucose-6-phosphate dehydrogenase deficiency, and resolved hepatitis B. Medications included acyclovir as prophylaxis for varicella zoster virus infection and omeprazole.

Examination revealed bilateral ankle oedema which was exquisitely tender to palpation. There were hyperpigmented macules and patches on both palms, lateral malleoli, and plantar surfaces of the feet (figure 1). Systemic examination was unremarkable.

Figure 1

(A) Hyperpigmentation of ankles with ankle oedema. (B) Clear fluid filled blister over the lateral malleolus. (C) Hyperpigmented macules on the plantar surfaces of the feet.

Investigations

Laboratory investigations showed a haemoglobin of 9.6 g/L (normal range 13.5–17.5 g/L), white cell count of 26×10⁹ /L (normal range 4–11 × 10⁹ /L), neutrophils of 15.5×10⁹ /L (normal range 2.0–7.5 × 10⁹ /L), C reactive protein of 27.6 mg/L (normal range <3.0 mg/L) and serum ACE of 70 U/L (normal range <40 U/L). Renal function was within normal limits. An autoimmune screen showed a raised speckled antinuclear antibody titre (1:640, normal range <1:40) and raised anti-Ro and anti-La antibody levels (>100 U/mL, normal range <20 U/mL), which were negative on previous testing prior to the development of ALV. Rheumatoid factor, antibodies to double-stranded DNA, other extractable nuclear antibodies (Sm, RNP, Scl-70, Jo1), antineutrophil cytoplasmic antibody (ANCA) and cryoglobulins were all negative. Viral serology was negative for hepatitis B surface antigen and positive for antibodies against hepatitis B core antigen and against hepatitis B surface antigen, indicating a resolved infection. Complement levels were normal. X-rays and ultrasound of the ankles were unremarkable. Serum and urine electrophoresis and bone marrow trephine showed no evidence of residual monoclonal gammopathy or myeloma.

Incisional biopsy from the ankle revealed full-thickness epidermal necrosis with vascular thrombosis affecting the capillaries, mural fibrinoid change and neutrophils with leucocytoclasia (figure 2). This was consistent with a diagnosis of ALV with secondary epidermal infarction.

Figure 2

(A) Largely intact epidermis on the right side with infarcted epidermis on the left side resulting in pale staining and loss of cell definition. The underlying dermal vessels are mostly packed with thrombus (H&E×10). (B) Typical focus of acute leucocytoclastic vasculitis (H&Ex20).

Differential diagnosis

The differential diagnosis included other causes of vasculitis including cutaneous sarcoidosis, ANCA-associated vasculitis, systemic lupus erythematosus (SLE), Sjögren syndrome and mixed cryoglobulinaemia. However, the temporal association between G-CSF and the onset of symptoms, which was consistent with previous reports,3 and the rapid improvement after G-CSF discontinuation, pointed to G-CSF as the most likely culprit of the vasculitis. Furthermore, the patient’s sarcoidosis was well controlled, and he denied any classical symptoms of connective tissue disorders. Negative laboratory evaluation also helped exclude ANCA-associated vasculitis and mixed cryoglobulinaemia.

Treatment

G-CSF was discontinued. He was started on a 2-week course of oral prednisolone, and morphine and paracetamol for analgesia.

Outcome and follow-up

He made a rapid clinical improvement and was discharged on a tapering course of prednisolone 2 days after starting treatment. Full resolution of the rash was achieved after 2 weeks.