ACDIS insight: Understanding graft-versus-host disease

by Lynette Byerly, BSN, RN, CCDS, CCS

Graft-versus-host disease (GVHD) is an immune-mediated complication that occurs when donor immune cells, specifically T lymphocytes, attack the tissues of the recipient (host). It is most commonly associated with bone marrow and hematopoietic stem cell transplantation, though it can occur following blood transfusion or any organ transplant containing white blood cells. GVHD can occur even when a donor and a recipient are well-matched; the greater the mismatch, the higher the risk.

Clinical presentation

GVHD presents in two distinct forms based on timing of onset:

• Acute GVHD appears within two months of transplantation and may affect:
  
  • Skin (rash on palms and soles, potentially progressing to desquamation)
  • Gastrointestinal tract (bloody diarrhea)
  • Liver (elevated bilirubin)
• Chronic GVHD occurs more than three months after transplant and produces a similar skin rash, along with mouth lesions, hair loss, and liver and lung damage.

Acute GVHD may progress into the chronic form, which can persist for years. Both forms increase susceptibility to infection.

Treatment typically involves corticosteroids, immunosuppressants, antibiotics, and immunoglobulins. Ruxolitinib is a kinase inhibitor blocking JAK1 and JAK2 (Janus kinase proteins that regulate cell growth, immune responses, and blood cell production) signaling pathways; approved for acute GVHD in patients with inadequate response to corticosteroids.

Transfusion-associated GVHD

According to the American Hospital Association (AHA) ICD-9-CM Coding Clinic, Fourth Quarter 2008, pp. 97-100, in the section titled “Graft Versus Host Disease,” GVHD associated with blood transfusion is rare but carries a high mortality rate following transplantation. This occurs because, under normal circumstances, donor lymphocytes are destroyed by the recipient's immune system before mounting a response.

However, immunodeficient recipients or specific partial Human Leukocyte Antigen (HLA) matching (as with first-degree relative donors) can allow this protective response to fail. Onset occurs within three to 30 days post-transfusion, with manifestations similar to bone marrow-related GVHD.

While no effective treatments exist, gamma irradiation of cellular blood components can help prevent transfusion-associated GVHD.

ICD-10-CM/PCS coding considerations

For a patient with peripheral neuropathy secondary to chronic GVHD, since no direct index pathway exists to code G63, Polyneuropathy in diseases classified elsewhere, the correct code assignment is:

• T86.09, Other complications of bone marrow transplant
• D89.811, Chronic graft-versus-host disease
• G63, Polyneuropathy in diseases classified elsewhere

Bronchiolitis obliterans and bronchiolitis obliterans syndrome, a known complication of GVHD, can occur after hematopoietic stem cell transplantation, leading to significant respiratory issues. Subcategory J44.8, Other specified chronic obstructive pulmonary disease, includes:

• J44.81, Bronchiolitis obliterans and bronchiolitis obliterans syndrome

Bronchiolitis obliterans (BO) is an obstructive lung disease affecting the bronchioles, the smallest airways in the lungs, characterized by inflammation, damage, and scarring. It can result from infections, inhalation of toxic chemicals, or systemic/autoimmune disease.

Most commonly, however, it occurs as a pulmonary manifestation of chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation, or as a manifestation of chronic lung allograft dysfunction after lung transplantation. When BO occurs following lung or hematopoietic stem cell transplantation, it is referred to as bronchiolitis obliterans syndrome.

T-cell depleted hematopoietic stem cells for transplantation

PCS Table 302 (Administration) includes the substance value U, Stem Cells, T-cell Depleted Hematopoietic, for use with body part values 3 (Peripheral Vein) or 4 (Central Vein). This substance is reported with one of three qualifier values to specify the allogeneic donor source:

• 2 (Allogeneic, Related)
• 3 (Allogeneic, Unrelated)
• 4 (Allogeneic, Unspecified)

Allogeneic hematopoietic stem cell transplants are used to treat blood cancers such as leukemia, multiple myeloma, and certain lymphomas. Sources include HLA-identical sibling donors, other related donors, and unrelated donors. The risk of GVHD is increased when cells come from unrelated or other related donors compared to HLA-identical sibling donors. T-cell depleted stem cell transplants are one method to reduce GVHD risk; the depletion procedure occurs following apheresis and prior to infusion of the cells.

Coding scenario: liver transplant with acute GVHD

A patient develops a generalized macular rash, diarrhea, and ascites on day 50 following an orthotopic liver transplant, with a skin biopsy confirming acute GVHD via donor lymphocytes.

Under ICD-10-CM guidance, this scenario was coded as follows (with given information):

• T86.49, Other complications of liver transplant
• D89.810, Acute graft-versus-host disease
• L53.9, Unspecified erythematous condition (macular rash)
• R19.7, Diarrhea, unspecified
• R18.8, Other ascites
• 0HB0XZX, Excision of skin, external approach, diagnostic (skin biopsy)

Under current ICD-10-CM/PCS guidelines, the underlying transplant complication, the GVHD diagnosis, and each associated manifestation (skin disorder, diarrhea, ascites) should all be reported, along with the appropriate root operation code for the skin biopsy.

Important coding principle

Disease relapse (such as hematopoietic or lymphatic malignancy) following bone marrow or stem cell transplant is not classified as a transplant complication. Only regimen-related problems, including GVHD, graft rejection, infection, and gastrointestinal or hepatic complications are coded as complications. Relapse cases should instead be coded with the appropriate malignancy code and a code identifying the organ or tissue replaced by transplant, with the reason for the encounter (e.g., admission for chemotherapy) as the principal/first-listed diagnosis.

Editor’s note: Byerly is a CDI education specialist at ACDIS/HCPro. Contact her at lynette.byerly@hcpro.com.