Faculty Bibliography

LEARNING OBJECTIVE #1: Review Cutaneous Leukocytoclastic Vasculitis and its association with malignancy CASE: A 70 year-old man with diabetes presented with a lower extremity rash for two days. Five weeks prior to presentation, he experienced pharyngitis and rhinorrhea, resolving spontaneously. Two weeks later, he began to feel generalized weakness and fatigue. Two days prior to presentation, he had intense pruritus of his feet, and shortly thereafter developed purple lesions on the plantar surfaces, at which point he presented to the hospital. On presentation, physical exam showed multiple tender erythematous and violaceous nonblanchable macules coalescing on his lower extremities and back. Laboratory evaluation was notable for creatinine 1.0mg/dL, c-reactive protein 40mg/L and erythrocyte sedimentation rate 130mm/hr. Anti-nuclear antibody, rheumatoid factor, P-ANCA, C-ANCA, SS-A/SS-B, IgA and cryoglobulin were negative. C3 was normal and C4 was slightly elevated. Infectious evaluation was negative for hepatitis B and C, with an elevated antistreptolysin O. Skin biopsy showed leukocytoclastic vasculitis, though direct immunofluorescence was unavailable. Our patient was diagnosed with Cutaneous Leukocytoclastic Vasculitis (CLV) once other connective tissue disorders were excluded and with reassurance that visceral organs were not affected. This case was likely related to a recent respiratory infection, however underlying malignancy was not excluded. The patient received oral steroids, and was discharged to complete a malignancy work-up. IMPACT: This case reminds us to consider associations between pathologies. For this patient, it was not sufficient to make the diagnosis of CLV, but we had to appreciate its association with malignancy in order to thoroughly manage this patient. DISCUSSION: Cutaneous LuekocytoclasticVasculitis (CLV) is a small vessel vasculitis limited to the skin. The pathophysiology is poorly understood, however it may be due to immune complex deposition and neutrophil migration resulting in the release of free radicals. CLV may be precipitated by infection, malignancy, medication or deemed idiopathic. Patients present with non-pruritic purpura predominantly in dependent areas, and may report constitutional symptoms. Pathologically, lesions appear as neutrophilic infiltration of the small vessels, and direct immunofluorescence reveals immune complex deposition containing C3, IgM, IgA and IgG. The diagnosis is made after excluding other vasculitides with visceral involvement. CLV may be considered a paraneoplastic process due to its association with malignancy. One study showed that 16 of 421 patients with CLV (3.8%) had an underlying malignancy, and the vasculitis appeared an average of 17 days before malignancy was diagnosed. Both solid organ and hematologic malignancies have been implicated, including chronic lymphocytic leukemia, urinary and gastrointestinal malignancies. CLV may also be associated with infections, including HIV, beta-hemolytic streptococcus, and endocarditis

A 49-year-old woman with cholangiocarcinoma metastatic to the lungs presented with new-onset unrelenting headaches. A lumbar puncture revealed malignant cells consistent with leptomeningeal metastasis from her cholangiocarcinoma. Magnetic resonance imaging (MRI) of the brain revealed leptomeningeal enhancement. An intrathecal (IT) catheter was placed and IT chemotherapy was initiated with methotrexate. Her case is notable for the rarity of cholangiocarcinoma spread to the leptomeninges, the use of IT chemotherapy with cytologic and potentially symptomatic response, and a possible survival benefit in comparison to previously reported cases of leptomeningeal carcinomatosis secondary to cholangiocarcinoma.