Importance: Granuloma annulare is typically a benign, self-limited disease. Atypical presentations have been reported in association with systemic disease, including malignancy. Such patients may require additional diagnostic studies to assess for underlying malignancy. We report a patient with extensive sporotrichoid granuloma annulare-like dermatitis in association with systemic B-cell lymphoma.

Observations: An 83-year-old man with a three-year history of progressive sporotrichoid annular plaques and nodules on the arm developed ipsilateral retroauricular palpable lymphadenopathy, the latter consistent with B-cell lymphoma. Multiple skin biopsies of the plaques and nodules revealed granuloma annulare-like dermatitis. Lesions were unresponsive to intralesional and intramuscular corticosteroids, antibiotics, and antifungal agents, but rapidly improved following initiation of rituximab to treat his underlying lymphoma.

Conclusions and Relevance: Atypical presentations of granuloma annulare including granuloma annulare-like dermatitis warrant evaluation for systemic malignancy in a subset of patients.

Anti-CD20 monoclonal antibodies (mAbs) have revolutionized the therapy of B cell lymphomas, but are only partially effective. While current genetic engineering and efforts are yielding mAbs with enhanced antibody-dependent cellular functions, these improvements are largely incremental and do not result in altering the tumor microenvironment and host immune cells to favor immune-mediated tumor destruction. We hypothesize that the efficacy of anti-lymphoma mAbs can be improved by linking these precise tumor-targeting vehicles to immunomodulatory substances for release within the tumor microenvironment. Toll-like receptor 9 (TLR9) agonist CpG oligodeoxynucleotides (ODN) are prime candidates for boosting anti-lymphoma immunity. Thus we aimed to characterize the activity and mechanisms of action of anti-CD20-CpG conjugates in a syngeneic immunocompetent model for B cell lymphomas.

We confirmed that anti-CD20-CpG conjugates can be purified from unconjugated antibody and CpG while maintaining biological activity. Confocal microscopy studies with fluorescently-labeled conjugates revealed cellular uptake on human CD20 expressing mouse lymphoma cells, suggesting CpG is able to enter the cell even when targeting a non-internalizing target. Lastly, conjugates had superior normal B cell depletion efficiency compared to rituximab; even in more resistant B cell compartments such as the peritoneal cavity.