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Case 35-2019: a 66-Year-Old Man with Pancytopenia and Rash

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Case 35-2019: a 66-Year-Old Man with Pancytopenia and Rash The new england journal of medicine Case Records of the Massachusetts General Hospital Founded by Richard C. Cabot Eric S. Rosenberg, M.D., Editor Virginia M. Pierce, M.D., David M. Dudzinski, M.D., Meridale V. Baggett, M.D., Dennis C. Sgroi, M.D., Jo‑Anne O. Shepard, M.D., Associate Editors Kathy M. Tran, M.D., Case Records Editorial Fellow Emily K. McDonald, Sally H. Ebeling, Production Editors Case 35-2019: A 66-Year-Old Man with Pancytopenia and Rash Marcela V. Maus, M.D., Ph.D., Mark B. Leick, M.D., Kristine M. Cornejo, M.D., and Valentina Nardi, M.D.​​ Presentation of Case Dr. Joshua Salvi (Medicine): A 66-year-old man with a history of pancytopenia was From the Departments of Medicine transferred to this hospital in the winter for evaluation of pancytopenia and rash. (M.V.M., M.B.L.) and Pathology (K.M.C., V.N.), Massachusetts General Hospital, The patient had been well until 1 year before admission, when episodic fevers and the Departments of Medicine (M.V.M., began to occur. Approximately 3 months before admission, fevers with a tempera- M.B.L.) and Pathology (K.M.C., V.N.), Har‑ ture of up to 38.3°C increased in frequency and severity and coincided with shak- vard Medical School — both in Boston. ing chills. Scattered papules developed on the arms and legs; the lesions were N Engl J Med 2019;381:1951-60. initially deeply erythematous, but over a period of several days, the discoloration DOI: 10.1056/NEJMcpc1909627 faded and the skin sloughed. There was no associated pruritus, and febrile epi- Copyright © 2019 Massachusetts Medical Society. sodes did not coincide with worsening of the skin lesions. Two months before admission, episodes of orthostatic hypotension and dizzi- ness developed. The patient was admitted to other hospitals on two occasions for recurrent lightheadedness. Laboratory evaluation reportedly revealed a normal level of corticotropin in the blood and a normal increase in the serum cortisol level after intravenous administration of cosyntropin. The white-cell count was 850 per microliter (reference range, 4200 to 9900), the hemoglobin level 9.2 g per deciliter (reference range, 13.0 to 17.4), the platelet count 61,000 per microliter (reference range, 140,000 to 440,000), and the mean corpuscular volume 89 fl (reference range, 82 to 100). The blood levels of aspartate aminotransferase and alanine amino- transferase were elevated. Serologic tests for hepatitis A, B, and C viruses and for human immunodeficiency virus (HIV) type 1 and type 2 were negative. The fer- ritin level was 12,620 ng per milliliter (reference range, 30 to 400), but subsequent testing for the HFE mutation most often associated with hemochromatosis was negative. Nineteen days before the ferritin level was measured, the iron level was 67 μg per deciliter (12 μmol per liter) (reference range, 45 to 182 μg per deciliter [8 to 33 μmol per liter]), the total iron-binding capacity 143 μg per deciliter (26 μmol per liter) (reference range, 261 to 478 μg per deciliter [47 to 86 μmol per liter]), the transferrin saturation 47% (reference range, 20 to 55), the folate level 18.3 ng per milliliter (41 nmol per liter) (reference range, 6 to 20 ng per milliliter [14 to n engl j med 381;20 nejm.org November 14, 2019 1951 The New England Journal of Medicine Downloaded from nejm.org on November 13, 2019. For personal use only. No other uses without permission. Copyright © 2019 Massachusetts Medical Society. All rights reserved. The new england journal of medicine Table 1. Laboratory Data.* 8 Days before Reference Range, Admission, Reference Range, On Admission, Variable Other Hospital Other Hospital This Hospital† This Hospital Hemoglobin (g/dl) 13–17.4 9.2 13.5–17.5 9.8 Hematocrit (%) 38–50 26.1 41.0–53.0 28.2 Mean corpuscular volume (fl) 82–100 89.4 80.0–100.0 89.5 Platelet count (per μl) 140,000–440,000 58,000 150,000–400,000 51,000 White‑cell count (per μl) 4200–9900 800 4500–11,000 940 Differential count (%) Neutrophils 47–80 56 40–70 65.5 Lymphocytes 14–46 28 22–44 22.0 Monocytes 5–13 14 4–11 9.9 Reactive lymphocytes <1 2 0–8 Immature granulocytes 0 1.3 Erythrocyte morphologic features Presence of microcytes, Presence of burr cells macrocytes, ovalocytes, and schistocytes polychromasia, schisto‑ cytes, acanthocytes, and teardrop cells International normalized ratio 0.9–1.2 1.7 0.9–1.1 1.3 Partial‑thromboplastin time (sec) 24–36 70 Fibrinogen (mg/dl) 160–450 42 150–400 148 Thrombin time (sec) 11–15 38.8 D‑Dimer (ng/ml) <230 712 <500 4165 Lactate dehydrogenase (U/liter) 94–250 1,106 110–210 1301 Ferritin (ng/ml) 30 –400 13,026 20–300 29,600 Triglycerides (mg/dl) <150, fasting 378 40–150 685 Haptoglobin (mg/dl) 25–200 <20 30–200 <10 Sodium (mmol/liter) 133–145 127 135–145 127 Albumin (g/dl) 3.2–5.2 2.0 3.3–5.0 1.8 Globulin (g/dl) 2.0–3.5 2.6 1.9–4.1 3.2 Total bilirubin (mg/dl) 0–1 1.7 0.0–1.0 2.9 Alkaline phosphatase (U/liter) 39–117 500 45–115 604 Aspartate aminotransferase (U/li‑ 0–37 316 10–40 399 ter) Alanine aminotransferase (U/liter) 0–40 141 10–55 119 γ‑Glutamyl transferase (U/liter) 7–51 615 * To convert the values for triglycerides to millimoles per liter, multiply by 0.01129. To convert the values for bilirubin to micromoles per liter, multiply by 17.1. † Reference values are affected by many variables, including the patient population and the laboratory methods used. The ranges used at Massachusetts General Hospital are for adults who are not pregnant and do not have medical conditions that could affect the results. They may therefore not be appropriate for all patients. 45 nmol per liter]), and the vitamin B12 level 861 pg raphy revealed a small amount of pericholecystic per milliliter (635 pmol per liter) (reference range, fluid and mild edema in the right paracolic gut- 193 to 986 pg per milliliter [142 to 727 pmol per ter that suggested an infiltrative process; the liter]). Magnetic resonance cholangiopancreatog- biliary ducts appeared normal, and no intrahe- 1952 n engl j med 381;20 nejm.org November 14, 2019 The New England Journal of Medicine Downloaded from nejm.org on November 13, 2019. For personal use only. No other uses without permission. Copyright © 2019 Massachusetts Medical Society. All rights reserved. Case Records of the Massachusetts General Hospital A B D C Figure 1. Bone Marrow Biopsy Specimen and Aspirate. Hematoxylin and eosin staining of a core biopsy specimen (Panel A) and May–Grünwald–Giemsa staining of aspirate (Panels B and C) obtained at the other hospital show numerous histiocytes with engulfed erythroid elements (Panel B) and mature red cells (Panel C). Immunohistochemical staining for CD163 shows histiocytes filled with intracyto‑ plasmic red cells (Panel D). Dashed lines outline hemophagocytic histiocytes. patic iron deposition was seen. The orthostatic nically poor quality but showed normal biven- hypotension abated, but did not fully resolve, tricular function; valvular dysfunction was not after the administration of intravenous fluids. assessed. Radiography of the chest revealed atelec- The patient was discharged home and was in- tasis but was otherwise normal. Computed to- structed to follow up with his primary care mography (CT) of the chest, performed after the physician. administration of intravenous contrast material, Eight days before admission, orthostatic hypo- revealed small bilateral pleural effusions and no tension recurred. The patient was readmitted to evidence of lymphadenopathy; CT of the abdo- one of the other hospitals, where he reported on- men and pelvis revealed normal hepatic paren- going lightheadedness and generalized weakness. chyma, a moderate amount of ascites, mild The temperature was 36.6°C, the pulse 91 beats splenomegaly, and no evidence of lymphade- per minute, the blood pressure 119/71 mm Hg nopathy. Positron-emission tomography (PET) while the patient was in the supine position from the skull base to the thighs, performed (75/48 while he was standing), the respiratory after the administration of intravenous 18F-fluoro- rate 16 breaths per minute, the oxygen satura- deoxyglucose (FDG) tracer, revealed homoge- tion 95% while he was breathing ambient air, neous FDG uptake in the spleen, and there was and the weight 74.9 kg. He was pale, appeared no evidence of hypermetabolism in the abdomi- ill, and had marked edema of the legs and peri- nal or pelvic lymph nodes. orbital region. Scattered nummular and erosive The patient was transferred to this hospital lesions with overlying eschar were noted on both for further evaluation and management of possi- feet, both forearms, and the medial right thigh; ble hemophagocytic lymphohistiocytosis (HLH). petechiae were also seen on the arms and chest. Dr. Valentina Nardi: Examination of a bone The remainder of the examination was normal. marrow biopsy specimen and aspirate that were Laboratory test results are shown in Table 1. An obtained at the other hospital revealed maturing antibody-based screening test for Lyme disease trilineage hematopoiesis and mildly hypercellu- was negative, as were nucleic acid tests for babesia, lar marrow with many histiocytes and numerous ehrlichia, anaplasma, adenovirus, and cytomega- engulfed erythroid elements in the cytoplasm. lovirus. Histoplasma and aspergillus antigens The findings were consistent with hemophago- were not detected in the blood. Cultures of the cytosis, with no evidence of infection or lym- blood were negative. phoma (Fig. 1).
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