Secondary ADRs Related to Therapeutic Immunosuppression

Bacterial infections often contribute to morbidity and mortality associated with therapeutic immunosuppression.14,16 A wide range of bacteria, including odontopathic, peri-odontopathic, and transient pathogens of the oral flora may manifest as ulcerative lesions. The normal signs of infection such as inflammation are not always obvious, with pain, fever, and the presence of a lesion observed most consistently (Figure 18).

Figure 18. Coagulase-negative Staphylococcal Infection in a Patient with Leukemia Undergoing Chemotherapy.

Photo of coagulase-negative staphylococcal infection in a patient with leukemia undergoing chemotherapy.

Therapeutic immunosuppression is often complicated by fungal infections such as those associated with the Candida sp.14,16 Oral candidiasis may appear as white, raised, or cottage cheese-like growths that can be scraped off, leaving a red and sometimes hemorrhagic base. Via deglutition, droplet aspiration, or the hematological route oral candidiasis may spread to the esophagus or lungs; and, eventually, may affect all organ systems (Figures 19 and 20).

Figure 19.

Photo of severe oral infection with candidal organisms in a patient undergoing immunotherapy prior to bone marrow transplantation.

Figure 20.

Photo of severe dermal and nail infection with candidal organisms in a patient undergoing immunotherapy prior to bone marrow transplantation.

Severe oral, dermal, and nail infection with candidal organisms in a patient undergoing immunotherapy prior to bone marrow transplantation.

Viral infections in patients undergoing therapeutic immunosuppression include recurrent herpes simplex virus (HSV) infections affecting the lips and intraoral tissues (Figure 21).16 The ulcerations are quite painful. The optimal period of observation for the detection of recurrent HSV infections is during the 7- to 14-day period following immunosuppression. Primary HSV infections account for less than 2% of infections in this patient population.

Figure 21. Atypical Herpes Labialis Secondary to the Reactivation of the Latent HSV in a Patient with Leukemia Undergoing Chemotherapy.

Photo of atypical herpes labialis secondary to the reactivation of the latent HSV in a patient with leukemia undergoing chemotherapy.

Herpes zoster (HZ) is a common clinical manifestation of immunosuppression-induced reactivation of the latent varicella zoster virus.16 It is a localized, painful vesicular rash with an erythematous base restricted to skin and mucosal tissues and follows the distribution of a branch of the trigeminal nerve (Figures 22 and 23). Lesions are usually unilateral, deeper seated and more closely aggregated than those associated with chickenpox.

Figure 22.

Photo of herpes zoster infection involving the maxillary and ophthalmic divisions of the trigeminal nerve secondary to the reactivation of the latent VZV in a patient with leukemia undergoing chemotherapy.

Figure 23.

Photo of herpes zoster infection involving the maxillary and ophthalmic divisions of the trigeminal nerve secondary to the reactivation of the latent VZV in a patient with leukemia undergoing chemotherapy.

Herpes zoster infection involving the maxillary and ophthalmic divisions of the trigeminal nerve secondary to the reactivation of the latent VZV in a patient with leukemia undergoing chemotherapy.

Epstein-Barr virus (EBV) infection has been associated with a wide range of syndromes in solid organ transplant recipients. In the oral cavity, the EBV has been causally related to hairy leukoplakia, characteristically found on the lateral borders of the tongue in patients with therapeutic immunosuppression (Figure 24). As noted earlier, the EBV is an oncogenic virus, which when reactivated may also cause secondary malignancies.

Figure 24. Hairy Leukoplakia Secondary to the Reactivation of the Latent EBV in a Patient on Therapeutic Immunosuppression Following Renal Transplantation.

Photo of hairy leukoplakia secondary to the reactivation of the latent EBV in a patient on therapeutic immunosuppression following renal transplantation.

Secondary malignancies related to therapeutic immunosuppression in susceptible individuals include de novo squamous cell carcinoma of the skin and lip (Figure 25).16 Secondary malignancies related to immunosuppression-induced reactivation of oncogenic viruses include Kaposi sarcoma (Figure 26), lymphoproliferative diseases (Figure 27), Hodgkin's and non-Hodgkin’s lymphomas, and spindle-cell sarcoma (Figure 28).16

Figure 25. Squamous Cell Carcinoma of the Lip in a Patient 2 Years After Renal Transplantation.

Photo of squamous cell carcinoma of the lip in a patient 2 years after renal transplantation.

Figure 27. Epstein-Barr Virus-related Lymphoproliferative Disease in a Patient 3 Years After Renal Transplantation.

Photo of Epstein-Barr virus-related lymphoproliferative disease in a patient 3 years after renal transplantation.

Figure 26. Human Herpesvirus-8-related Kaposi Sarcoma of the Palate in a Patient 4 years After Renal Transplantation.

Photo of human herpesvirus-8-related Kaposi sarcoma of the palate in a patient 4 years after renal transplantation.

Figure 28. Epstein Barr Virus-related Spindle Cell Sarcoma in a Patient 4 Years After Renal Transplantation.

Photo of Epstein Barr virus-related spindle cell sarcoma in a patient 4 years after renal transplantation.