Paraneoplastic pityriasis rubra pilaris heralding onset of new hematologic malignancy
Authors: Ruby B. Kwak, Farhaan Hafeez, Christine Lian, Vinod E. Nambudiri
Journal: American Journal of Hematology (2020)

A 72-year-old woman who was recently diagnosed with high-risk myelodysplastic syndrome (MDS) presented with a 1-month history of a diffuse pink, scaly, and pruritic rash. She first noticed mild skin eruptions primarily on her chest 6 months prior to presentation. The rash spread progressively to most of the bilateral arms, torso, proximal thighs, and eventually the bilateral palms. Her face, feet, nails, and mucosal surfaces were spared. The lesions never bled, ulcerated, or formed blisters. There were no other symptoms except for mild fatigue for several weeks. She had no new medications or recent exposure to allergenic materials, or a history of similar cutaneous eruptions in the past. She had been found to have new leukopenia and anemia at a routine clinic visit 4 months prior (approximately 2 months after the onset of her initial rash). One week prior to presentation, she had undergone a bone marrow biopsy that suggested high-risk MDS. She was relatively asymptomatic except for the cutaneous eruptions, which she had not been evaluated for until this presentation. On exam, the arms, chest, back, and thighs revealed numerous pink-orange patches with diffuse scales (Image 1A-C). Her palms demonstrated light pink-brown papules and plaques with waxy hyperkeratosis (Image 1D). Skin biopsies demonstrated spongiotic dermatitis with pityriasiform scale and a superficial perivascular lymphocytic infiltrate, comprised mostly of lymphocytes and scattered eosinophils (Image 2A-C). The clinical and pathologic findings were consistent with a diagnosis of pityriasis rubra pilaris (PRP), and she was diagnosed with paraneoplastic PRP secondary to her hematologic malignancy. She was initiated on decitabine for her MDS and was treated with topical betamethasone 0.05% cream and topical urea for symptom relief. Her cutaneous symptoms were mostly resolved following the second cycle of decitabine and 2 months of topical therapy (Image 1E,F). Pityriasis rubra pilaris is an inflammatory papulosquamous dermatosis characterized by hyperkeratotic follicular papules, orange-red plaques with scales, and palmoplantar hyperkeratosis. Well-demarcated areas of sparing and erythroderma are also common findings.1 Pathogenesis is unknown, however, an up-regulation of the tumor necrosis factor (TNF) alpha has been postulated as a possible cause.2 Abnormal vitamin A metabolism, infection, and genetic predispositions are additional factors thought to cause PRP.1 Skin biopsies are typically obtained to aid in the diagnosis of PRP, which requires clinical and histopathologic correlation. Biopsy classically demonstrates alternating orthokeratosis and parakeratosis of the stratum corneum, perivascular lymphohistiocytic infiltrate in the dermis, epidermal acanthosis, focal hypergranulosis, thick supra-papillary plates and an intact granular layer.1 Various non-classical features have also been described including dermal eosinophilia (as seen in this patient), lichenoid infiltrates, and acantholysis.1 Paraneoplastic PRP is a rarely occurring phenomenon, with fewer than 20 cases reported in the literature. It is rarely associated with hematologic malignancies. In all but one case, paraneoplastic PRP was associated with solid organ malignancies such as hepatocellular carcinoma, renal cell carcinoma, and colon cancer.3-6 One prior case described PRP in association with acute leukemia of undifferentiated type.7 Our case demonstrates the first reported case of paraneoplastic PRP in association with MDS. The pathogenesis of paraneoplastic PRP is poorly understood. It is thought that the paraneoplastic manifestations of the skin may be driven by the overproduction of growth factors by the underlying malignancy. In addition, the immunologic responses triggered by underlying cancer and the antigen cross-reactivity with the skin are thought to be implicated.8 Treatments for PRP may include topical corticosteroids, oral retinoids (vitamin A derivatives), methotrexate, anti-TNF-alpha inhibitors, cyclosporine, azathioprine, and phototherapy.1 Unfortunately, their use is largely based on anecdotal evidence and case reports, as there is no FDA approved PRP treatment currently available. Management of paraneoplastic PRP generally has treatment of the underlying malignancy as the primary approach, with topical agents added for symptomatic relief such as in this patient. Chemotherapy, radiotherapy, and surgical resections targeted at the underlying malignancy were shown to be effective in clearing the cutaneous symptoms.3 We present this case to highlight the recognition of this uncommon cutaneous eruption as a paraneoplastic dermatosis.