A 47-year-old man comes to the physician with skin changes and joint pain. He underwent human leukocyte antigen-matched allogeneic stem cell transplant for acute myeloid leukemia from his sister 1 year ago and was treated with methotrexate, sirolimus, and prednisone postoperatively. Prednisone was tapered off and stopped 6 months ago. Two months ago, he noticed progressively worsening skin changes. He has difficulty using his fingers and complains of small joint pain. He currently uses artificial tears for eye dryness and albuterol as needed for mild intermittent asthma.
Vital signs are within normal limits. Skin examination shows extensive skin thickening with areas of hypopigmentation (Exhibit). The hand joints have limited mobility without redness or swelling. The remainder of the examination is within normal limits.
Laboratory results are as follows:

Which of the following is the most likely diagnosis?

Question

A 47-year-old man comes to the physician with skin changes and joint pain.  He underwent human leukocyte antigen-matched allogeneic stem cell transplant for acute myeloid leukemia from his sister 1 year ago and was treated with methotrexate, sirolimus, and prednisone postoperatively.  Prednisone was tapered off and stopped 6 months ago.  Two months ago, he noticed progressively worsening skin changes.  He has difficulty using his fingers and complains of small joint pain.  He currently uses artificial tears for eye dryness and albuterol as needed for mild intermittent asthma.
Vital signs are within normal limits.  Skin examination shows extensive skin thickening with areas of hypopigmentation (Exhibit).  The hand joints have limited mobility without redness or swelling.  The remainder of the examination is within normal limits.
Laboratory results are as follows:

Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec193a_983d_62cd_853d_31dda5759f37_MD0002_00 This patient's clinical presentation suggests chronic graft-versus-host-disease (GVHD). GVHD occurs when transplanted non-identical donor immune cells (usually T lymphocytes) recognize the transplant recipient cells (host) as foreign and initiate an immune reaction. Acute GVHD occurs within 100 days of hematopoietic cell transplantation (HCT); chronic GVHD can occur any time after HCT. Acute GVHD involves strong inflammatory components; chronic GVHD has more autoimmune and fibrotic features. Acute GVHD presents with a painful maculopapular rash that can progress to toxic epidermal necrolysis, abdominal pain, diarrhea, and elevated liver enzymes (eg, bilirubin, alkaline phosphatase). This syndrome typically occurs within a median time of 19 days after HCT. Risk factors include human leukocyte antigen mismatch or unrelated donor, gender disparity (eg, female donor to male recipient), and lack of prophylactic GVHD regimen (eg, methotrexate, cyclosporine). Chronic GVHD resembles an autoimmune vascular disease and can occur in up to 50% of HCT patients at any time after transplant (median of 201 days post HCT). Risk factors include older age of donor/recipient, prior acute GVHD, or seropositive cytomegalovirus in either donor or recipient. Patients usually present with a skin rash resembling lichen planus or scleroderma with areas of hypo- or hyperpigmentation. Other features include increased liver function tests (eg, bilirubin, alkaline phosphatase), dry oral mucosa with ulcerations, dry eyes with possible cataracts, bronchiolitis obliterans, esophageal webs/strictures, and fasciitis or joint strictures. Diagnosis is usually clinical but may require skin or gastrointestinal biopsy. Glucocorticoids are preferred for acute GVHD. Localized therapy (eg, topical steroids for skin involvement, cyclosporine eye drops) is preferred for limited chronic GVHD. Extensive chronic GVHD requires systemic steroids with cyclosporine or tacrolimus. (Choice A) Eosinophilic fasciitis usually presents with acute, marked, symmetrical, nonpitting edema that spares the hands and feet. The edema eventually resolves and is replaced by skin induration and puckering with orange peel (peau d'orange) texture. There is also prominent peripheral eosinophilia. (Choice C) Nephrogenic systemic fibrosis/dermatopathy is a rare syndrome that occurs in patients with acute/chronic kidney disease who are exposed to gadolinium contrast. It involves the skin (with bilateral fibrotic, indurated papules) and other systemic organs. This patient's stable creatinine and absence of contrast exposure make this less likely. (Choice D) Skin changes in systemic sclerosis include telangiectasias, sclerodactyly, digital ulcers, and calcinosis cutis. Patients may also report vascular symptoms such as Raynaud phenomenon, gastrointestinal symptoms such as gastroesophageal reflux, or shortness of breath suggesting lung involvement. Educational objective: Acute graft-versus-host disease occurs within 100 days of hematopoietic stem cell transplant; chronic graft- versus-host disease can occur at any time. The skin, liver, and gastrointestinal tract are most commonly affected. Treatment includes steroids for both acute and chronic disease. __________ References: Graft-versus-host disease. (http://www.ncbi.nlm.nih.gov/pubmed/19282026) Concise review: acute graft-versus-host disease: immunobiology, prevention, and treatment. (http://www.ncbi.nlm.nih.gov/pubmed/23283494) How I conduct a comprehensive chronic graft-versus-host disease assessment. (http://www.ncbi.nlm.nih.gov/pubmed/21719600)

A 47-Year-Old Man Comes to the Physician with Skin Changes