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# Ibrutinib-related stellar hematomas of the palms and soles

Naia Oillarburu, Loic Ysebaert, Caroline Protin, Ariadna Ortiz-brugues, Sarah Baali, Estelle Parriel, Vincent Sibaud

► To cite this version:

Naia Oillarburu, Loic Ysebaert, Caroline Protin, Ariadna Ortiz-brugues, Sarah Baali, et al.. Ibrutinib-related stellar hematomas of the palms and soles. American Journal of Hematology, 2024, 100 (5), pp.894 - 896. 10.1002/ajh.27514. inserm-05247435

HAL Id: inserm-05247435

https://inserm.hal.science/inserm-05247435v1

Submitted on 9 Sep 2025

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# Ibrutinib-related stellar hematomas of the palms and soles

Naia Oillarburu<fnref n="1" /> ID | Loic Ysebaert<fnref n="2" /> ID | Caroline Protin<fnref n="2" /> | Ariadna Ortiz-Brugues<fnref n="1" /> | Sarah Baali<fnref n="1" /> | Estelle Parriel<fnref n="1" /> | Vincent Sibaud<fnref n="1" />

Correspondence

Naia Oillarburu, Department of Oncodermatology, Institut Universitaire du Cancer-Oncopole, 1 avenue Irène Joliot Curie, 31059 Toulouse, France.

Email: n.oillarburu@gmail.com

<figure><img src="image_3.png" /><figcaption>**FIGURE 1** Stellar punctiform hemorrhagic lesions on the palms, located on the thenar and hypothenar eminences and the fingertips.</figcaption></figure>

Bruton's tyrosine kinase (BTK) inhibitors represent a major break-
through in the treatment of chronic lymphocytic leukemia (CLL) or
other B cell malignancies (e.g., mantle cell lymphoma, Waldenstrom's
macroglobulinemia, marginal zone lymphoma), and graft versus host
disease (GVHD). Ibrutinib is the first-in-class oral small-molecule BTK
inhibitor that acts by covalent and irreversible binding to BTK, a
Transient Erythroblastopenia of Childhood (TEC) family non-receptor
tyrosine kinase. Although ibrutinib presents a favorable safety profile,
it can be associated with adverse events, including dermatological tox-
icities which affect more than one third of patients.<fnref n="1" /> In this context,
the progressive development of hematomas and bruising is clearly
the most representative dermatological toxicity associated with BTK
inhibitors, but a wide range of other skin manifestations have been
also reported, including bacterial/fungal skin infections, folliculitis,
maculopapular rash, eczema-like reactions, brittle nails with onychoschi-
zia and onycholysis, paronychia, pruritus/xosis, mild to moderate
alopecia, stomatitis, or panniculitis.<fnref n="1" />⁻⁴

We describe here for the first time a new dermatological adverse
event related to ibrutinib, with the occurrence in two patients of vas-
cular lesions in the form of diffuse stellar hematomas involving the
palms and soles exclusively.

A 76-year-old female patient was diagnosed with CLL in January 2008. She was treated with a geno-identical allograft in July 2008 at the age of 59 years old, complicated by cutaneous graft versus host disease and sequellar hypogammaglobulinemia. Her CLL relapsed in 2017, with hyperlymphocytosis of approximately 100 G/L and no palpable tumor syndrome. The characteristics of her CLL showed a karyotype with a t(3; 12) translocation, no ATM or P53 gene deletion, negative molecular biology, and mutated IGVH status. BTK inhibitor ibrutinib was introduced at a total dose of 420 mg once a day. In December 2019, total dose was decreased to 280 mg/day due to atrial fibrillation.

Then, ibrutinib was stopped in October 2020 for fungal sinusitis
(mucormycosis) with secondary bacterial superinfection. Resumption

<footnote n="1">¹Department of Oncodermatology, Institut Universitaire du Cancer-Oncopole, Toulouse, France</footnote>

<footnote n="2">²Department of Hematology, Institut Universitaire du Cancer-Oncopole, Toulouse, France</footnote>
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of ibrutinib was decided in August 2021, 140 mg/d reduced to 1 dose every other day.

Three years later, during a follow-up visit asymptomatic stellar vascular lesions on the palms and to a lesser extent to the soles were noticed. These punctiform hemorrhagic lesions were distributed bilaterally. On the hands, the lesions were predominantly located on the thenar and hypothenar eminences and the fingertips (Figure 1).

A 73-year-old patient suffered from CLL since January 2014. CLL was characterized by a 17p deletion and non-mutated IGHV status. She was treated in first-line therapy with combination of rituximab and PI3K inhibitor idelalisib from January to September 2016 which had to be discontinued due to severe toxicity (i.e., grade IV neutropenia and colitis). Second-line therapy with ibrutinib was introduced on year later, at a dose of 420 mg/day, followed by a dose reduction (140 mg/day) after several episodes of skin and osteoarticular infections.

In June 2024, similar vascular stellar lesions of the palms, localized to the thenar eminence of both hands were individualized. No vascular lesions were noted on soles (Figure 1).

For these two patients, the lesions were totally asymptomatic and not associated with other hemorrhagic manifestations of the treatment except mild bruising on the arms. No other individualized clinical, biological, and pharmaceutical triggering factors (except BTK inhibitor exposure) were individualized. Dermoscopy revealed similar aspects in both cases with confluent petechial purpuric lesions and a glomerular appearance in some areas (Figure 2). Ibrutinib therapy was continued at the same dose.

Petechiae and hematomas are the most common cutaneous adverse events of BTK inhibitors, affecting roughly a quarter of patients.¹ These lesions tend to develop more frequently in elderly patients with epidermal atrophy and dermatoporosis, with a privileged

bilateral distribution in areas of repeated microtrauma and/or chronic UV exposure such as the lateral aspect of the forearms and less commonly the trunk.¹,² They are possibly favored by concomitant use of systemic corticosteroids, antiplatelet agents, and oral anticoagulants. These lesions are promoted by a selective inhibition of platelet signaling and downstream functions of the glycoprotein VI receptor induced by ibrutinib, which strongly affects platelet adhesion on von Willebrand factor (VWF).⁵,⁶ In the same way, patients exposed to ibrutinib present an increased risk of bleeding,⁶ particularly older men with lower platelet count and on multiple anticoagulant therapies. Low grade skin bleeding has shown a dose-dependent response³; therefore, transient discontinuation of ibrutinib should be considered for dermatologic surgery, for example, three days before and after surgery.⁷,⁸

We can speculate that palmoplantar lesions developing in the two patients we have described are related to the same underlying vascular mechanism and are triggered by repeated localized microtraumas. The palmar predominance of these newly individualized hematomas could potentially be explained by the much greater plantar thickness of the stratum corneum with protective effects. Although its overall incidence has yet to be determined, it can be assumed that this newly described skin toxicity often goes unnoticed and is in practice fairly frequent. However, such stellar hematomas do not require specific treatment, only reassurance of the patients and their relatives. Finally, because next-generation BTK inhibitors such as acalabrutinib or zanubrutinib are able to interact with platelet aggregation⁹ and can also induce similar ecchymoses and bruising, we can speculate that development of such palmoplantar stellar hematomas may be also observed with these more selective targeted therapies.¹,¹⁰

<figure><img src="image_5.png" /><figcaption>FIGURE 2 Confluent petechial purpuric lesions and a glomerular appearance in dermoscopy.</figcaption></figure>
## CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

## DATA AVAILABILITY STATEMENT

The data support the findings on this study are available from the corresponding author upon reasonable request.

## ORCID

Naia Oillarburu https://orcid.org/0009-0004-4049-3097

Loic Ysebaert https://orcid.org/0000-0001-8478-5623

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**How to cite this article:** Oillarburu N, Ysebaert L, Protin C, et al. Ibrutinib-related stellar hematomas of the palms and soles. *Am J Hematol*. 2025;100(5):894-896. doi:10.1002/ajh.27514