44

CASE 44


FG, a 42-year-old patient with fulminant cardiac failure secondary to acute viral myocarditis, receives a heart (via UNOS) from a trauma victim. You are aware incidentally that the lungs, liver, and kidneys of the same donor have been used in other transplants around the globe.


The postoperative course for this patient is essentially unremarkable, and he is discharged home at 10 days after transplantation on a conventional immunosuppressive drug regimen. He returns through the emergency department 7 days later in acute respiratory distress, with oxygen saturation less than 85% and febrile. What are your thoughts, and what will you do?



QUESTIONS FOR GROUP DISCUSSION



1. Tissue rejection is of concern for any transplant patient. Explain this patient’s workup to investigate whether his symptoms are caused by hyperacute/ acute rejection.

2. Review the immunology of acute rejection and consider whether the kinetics suggest this is a likely cause of the clinical presentation. How is acute rejection generally treated? Would a biopsy help here? Discuss the rationale for the use of each of the following as therapy for acute rejection: (a) intravenous anti-CD3 antibodies and (b) anti-CD25 antibodies.

3. Early chronic rejection is a (less likely) possibility. How would the pathophysiology of chronic rejection help us understand a presentation of acute respiratory failure?

4. If a diagnosis of “rejection” is not supported by the results obtained, what other considerations come to mind in patients on potent immunosuppressive therapy?

5. Malignancies and drug toxicity are important considerations. Are these likely to account for the predominant symptoms seen at this time after transplantation? How might this patient develop such an early appearing malignancy (consider donor origin)?

6. Direct drug toxicity reactions are certainly a consideration. Often an idiosyncratic drug (hypersensitivity) reaction, independent of common drug toxicities, will lead to respiratory complications. Is this likely with a patient on high doses of corticosteroids?

7. You should consider (early) the likelihood of infectious complications. Discuss the type of infections to which this patient is susceptible and the potential source of these infections.

8. Transplant patients are at increased risk of death from severe acute respiratory syndrome (SARS) compared with the normal population. Explain. Also, why is SARS of particular concern for this particular patient?


RECOMMENDED APPROACH



Implications/Analysis of Family History


We are not provided with any family history for the patient.



Implications/Analysis of Clinical History


The myocarditis as the cause of his cardiac failure is a potential issue. Could this infection have recurred causing failure of the transplanted organ with resultant respiratory failure (secondary to cardiac failure)? History regarding possible CMV (cytomegalovirus/ human herpes virus 5) status before the transplant is worth knowing, as is the patient’s drug history (any risk factors for HIV [human immunodeficiency virus] or other unsuspected pathogens?).



Acute and Chronic Rejection


Acute rejection is certainly the most likely initial explanation readily correlated with symptoms and presentation. However a biopsy failed to find any evidence for this: there were no signs of lymphocyte infiltration into the organ, no biochemical markers of cardiac cell death (elevated cardiac enzymes), and no changes in the electrocardiogram.


Chronic rejection occurs with release of a variety of mediators, including fibroblast growth factor and endothelial growth factor, which can cause an insidious fibrosing/proliferative reaction relatively refractory to immunosuppressive treatment. This could affect the heart, causing secondary lung failure (and the respiratory distress). However, the kinetic picture (<4 weeks after transplant) does not suggest this as a likely explanation.



Organ-Specific Damage


The most likely organ-specific damage to be seen in this patient (4 weeks after transplant) is the heart. However, all markers of cardiac biochemistry/function look normal. The organ affected is the lung (not transplanted). Moreover, this patient has a fever not yet explained.


While we treat symptoms (urgent provision of respiratory support; workup of infectious causes) it is time to “expand our net” to include other diagnoses.



Implications/Analysis of Laboratory Investigation


Routine blood work, physical examination, electrocardiogram, and serum levels of cardiac enzymes should be initiated at this time. As noted, a number of cardiac enzymes (e.g., troponin I, creatine phosphokinase, creatine kinase) are released when heart tissue is damaged. Measurement of cardiac muscle enzymes was normal, as was the electrocardiogram, ruling out killing (lysis) of heart cells as the cause of this patient’s problem. You were unable to maintain this patient’s oxygen saturation above 90% without providing artificial breathing support (intubation and ventilation). A chest radiograph shows “patchy” infiltrates throughout the lung fields.



Side Effects of Drug Therapy


Could this disorder represent one of a possible number of side effects of the treatment he received for the transplant? In general, we know that chronically immunosuppressed populations show an increased frequency of malignancy, drug toxicity, and infections (Fig. 44-1).


image

FIGURE 44-1 Vascular sheathing, edema, necrosis, and hemorrhage of the retina, characteristic of cytomegalovirus retinitis.


(From Fireman P, Slavin R: Atlas of Allergies, 2nd ed. St. Louis, Mosby, 1996.)

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Jun 18, 2016 | Posted by in IMMUNOLOGY | Comments Off on 44

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