Leukemia Cutis As an Early Presentation or Relapsing Manifestation of Chronic Lymphocytic Leukemia

Introduction Cutaneous infiltration (Leukemia cutis) by CLL is regarded as specific sign of skin involvement, these findings can vary in presentations; they can be localized or generalized in the form of erythematous papules, plaques, nodules, and large tumors, however ulceration is uncommon. Skin lesions in general can be seen in 25% of patients with CLL. It is unclear what is the impact of cutaneous infiltration by CLL on prognosis, mainly because most cases are sporadic, either in case reports or series, with no consistency in the modality of treatment. Patients and methods A systematic search of the Medline database (PubMed), Google Scholar was performed to identify English language articles published from Jan 2000 to June 2019 with the following search terms: Leukemia cutis - CLL, cutaneous - CLL, skin - CLL, cutaneous - chronic lymphocytic leukemia, skin - chronic lymphocytic leukemia. Only patients with confirmed CLL Leukemia cutis were included in this analysis. Results A total of 56 cases were identified, with median age of 66 years (range from 39-90), of these cases 43 (76.8%) were males and 12 (21.4%) were females, with ratio of 3.6 : 1. Head and neck were the most common involved sites, interestingly it was very common on the earlobes, followed by trunk and extremities. The most common clinical presentation was papulonodular skin lesions, others like erythematous patches were seen, but ulceration was uncommon. Most cases had leukemia cutis as the initial presentation of CLL. The median time before relapse with skin involvement was 5.5 years (range 1 to 21 years). Most patients were diagnosed at early stage. Majority were treated with chemotherapy, others managed by observation, local radiotherapy or chemoimmunotherapy. In general, 35 (62.5%) cases had cutaneous response to treatment (25 CR and 10 PR). Discussion CLL skin infiltration is not uncommon, but it is not well described in the literature, here in our review we revisited specific cutaneous infiltration by CLL, we emphasized on Leukemia cutis rather than general secondary skin manifestations in CLL. Many cases had CLL skin involvement at the site of old herpetic lesions, which raises the hypothesis of monoclonal B-cells antigenic recruitment, rather than true metastasis. Most presentations came as first sign of the disease, and mostly in early stage. It was also observed that skin infiltration by CLL does not affect prognosis, as most patients attained complete or partial remission with very low progression rate. Because of the rarity of the disease, treatment modalities varied widely, and there was no consensus on treatment, yet all treatment modalities resulted in cutaneous response rate of 62.5%. The best modality of treatment in cutaneous CLL is based on the staging, lesions distribution (localized vs. generalized) and co-morbidities. Conclusion Leukemia cutis is rare but rather a recognized complication of CLL, most likely presents as papulonodular lesions as initial sign of the disease, furthermore most patients present in early stage, it is observed that all patients ≤60 year old had early stage disease, patients with early stage and localized leukemia cutis can benefit from observation alone strategy, on the other hand all patients with advanced stage were >60 year old, and intervention in these patients is warranted, in other situations treatment is individualized based on staging, lesions distribution (localized vs. generalized) and comorbidities. Leukemia cutis did not affect the prognosis of the disease. Disclosures No relevant conflicts of interest to declare.

Copovidone-related Cutaneous Response in the Dog

A cutaneous response (localized swelling and/or erythema of the skin) has been noted in dog toxicology studies in which multiple, unrelated compounds were administered orally with copovidone as a vehicle. The response has been noted in studies with 6 different test items that are structurally unrelated and span several different therapeutic indications spanning an approximate 6-year period (2009–2015). A factor common among the studies is the formulation—a copovidone amorphous solid dispersion (ASD). Cutaneous responses have not been observed in dogs administered non-ASD formulations of the same test items but have occasionally been noted in placebo (copovidone control) dogs. Polyvinylpyrrolidone (a polymer of one of the primary components of copovidone) has been reported to result in similar findings in dogs when administered by the intravenous route. Considerations for the role of copovidone and the potential role of histamine in the cutaneous changes are outlined.