Gardner–Diamond syndrome and the role of washed red cell intradermal test: A transfusion medicine perspective

While the aetiology remains unclear, the role of transfusion medicine specialists deserves renewed attention, particularly concerning the intradermal injection of autologous washed RBCs based on the hypothesis of auto-erythrocyte sensitization [6, 7]. A positive test is indicated by the development of a localized, tender ecchymotic lesion at the injection site within 24 h, while unaffected by control injections (e.g., saline) [8]. While washing may remove or alter the phosphatidylserine expression and potentially lower sensitivity, it improves specificity by removing plasma proteins and complement. This rationale follows Gardner and Diamond's original method, although comparative studies with whole blood could further clarify diagnostic yield. We present a case that underscores the diagnostic contribution of transfusion medicine specialists in such settings. A 43-year-old man came to the dermatology department with a history of recurrent, painful red patches over the legs of 3 months' duration (Figure 1). The lesions appeared spontaneously, associated with burning sensations, resolving over 8–12 days with transient hyperpigmentation. There was no history of trauma, bleeding diathesis, anticoagulant use or relevant family history. Vitamin C levels were not assessed, as routine testing is not standard practice; moreover, the patient had no clinical features suggestive of deficiency, making this unlikely. However, the patient had developed depressive symptoms following his mother's death 5 months earlier and was on antidepressants, which is considered a potential precipitating factor [9]. Cutaneous examination revealed a few ecchymotic patches at various stages, from bright erythematous to fading colour over bilateral thighs and legs. Initial investigations, including complete blood count, coagulation profile and antinuclear antibody tests, were unremarkable. Given the absence of an identifiable organic cause and the patient's history of depression, psychogenic purpura was considered. The transfusion medicine department prepared autologous washed RBCs (Figure 2) as follows: Under aseptic conditions in a laminar airflow hood, 2–4 mL of EDTA blood was centrifuged at 2500–3000 rpm for 5 min. Plasma was discarded, and two-thirds of the volume was replaced with sterile normal saline. The RBCs were gently resuspended and centrifuged again. This washing step was repeated two to three times. The final RBC pellet was resuspended in 0.1 mL sterile saline for immediate intradermal diagnostic use. The washed RBCs were injected intradermally by the dermatology team. A non-tender, non-indurated ecchymotic response was observed at the injection site within 24 h, thus making the test negative (Figure 1). This was our first institutional use of the test; although negative, it provided diagnostic direction and underscored its potential value in excluding the rare syndrome. Despite limited sensitivity and variable reproducibility, the intradermal washed RBC test, when interpreted within a multidisciplinary framework, provides diagnostic direction and reduces unnecessary investigations. A saline injection was used as a negative control; however, the absence of a standardized positive control limits reproducibility, as controls for rare diseases are not readily available. Moreover, the involvement of a transfusion medicine specialist in such non-traditional diagnostic applications emphasizes the specialty's expanding clinical relevance, and more such diagnostic applications are to be explored. Documenting such institutional experiences may aid in developing standardized diagnostic algorithms. As the specialty evolves beyond conventional blood support roles, its contribution to rare disease diagnosis and interdepartmental collaboration warrant greater recognition. Transfusion medicine specialists should be actively integrated into diagnostic teams addressing unexplained purpura, not only for their technical capabilities but also for their contribution to evidence-based and resource-appropriate diagnostic strategies. Informed consent was obtained from the patient. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. V.A.: writing-original draft, formal analysis, resources. A.V.N. and A.K.M.: resources, data curation. D.U.B. and A.R.: conceptualization, validation, supervision, writing-review and editing. D.K.: methodology, writing-review & editing. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.