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Hemophagocytic lymphohistiocytosis in a patient with Goodpasture's syndrome: a rare clinical association.

Basnet A, Cholankeril MR - Am J Case Rep (2014)

Bottom Line: This was initially attributed to the immunosuppressive effect of hydroxychloroquine.Here, we present a rare case of Goodpasture's syndrome with overlap and pauci-immune vasculitis, which may have triggered the HLH.This correlation has not been described before in the literature.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Trinitas Regional Medical Center, Seton Hall University of Graduate Medical Education, Elizabeth, USA.

ABSTRACT

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome. HLH can occur in the setting of an autoimmune disease, chronic immunosuppression, malignancy, and infection. We discuss a rare case of a young woman who was diagnosed with Goodpasture's syndrome that was most likely complicated by HLH. To the best of our knowledge, this is the first report of HLH in the setting of this rare autoimmune disease.

Case report: A 31-year-old woman who was diagnosed with Goodpasture's syndrome 7 years prior presented with febrile neutropenia. She was initially receiving treatment with azathioprine and prednisone, which was subsequently switched to hydroxychloroquine. Over time, she had developed polyarthritis and was later diagnosed with MPO-ANCA-positive vasculitides. On this admission, her clinical status deteriorated from persistent pancytopenia. This was initially attributed to the immunosuppressive effect of hydroxychloroquine. A bone marrow biopsy was performed and revealed hypercellular bone marrow without any cytogenetic abnormalities. Due to a prolonged pancytopenia thought to be of autoimmune etiology, treatment with high-dose steroids was initiated. With the persistent febrile episodes, hepatosplenomegaly on examination, and laboratory workup that revealed hyperferritinemia and pancytopenia, HLH syndrome was suspected. A repeat bone marrow biopsy confirmed this diagnosis with the presence of hemophagocytosis, demonstrated by the presence of histiocytes engulfing erythroid cells. She also met 5 of 8 diagnostic criteria, which confirmed the diagnosis of HLH. The patient eventually died despite aggressive treatment with high-dose steroid therapy for her autoimmune disorder, as well intravenous antibiotics and supportive care for her underlying infections.

Conclusions: HLH is a syndrome marked by a hyper-inflammatory state aggravated by specific triggers. To make the diagnosis of HLH, at least 5 of the 8 criteria must be met. Treatment involves suppression of the overwhelming inflammatory response by the use of immunomodulators. The mortality rate can range from 50-90% due to delayed recognition and onset of treatment. Here, we present a rare case of Goodpasture's syndrome with overlap and pauci-immune vasculitis, which may have triggered the HLH. This correlation has not been described before in the literature.

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H/E stain of bone marrow, demonstrating histiocytes with hemophagocytosis (engulfing erythrocytes indicated by the arrow) and with CD-68 staining positive cells in the insert. (Image courtesy of Dr. Heidi Fish).
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f3-amjcaserep-15-431: H/E stain of bone marrow, demonstrating histiocytes with hemophagocytosis (engulfing erythrocytes indicated by the arrow) and with CD-68 staining positive cells in the insert. (Image courtesy of Dr. Heidi Fish).

Mentions: Despite normal bone marrow biopsy results, she continued to have pancytopenia. High-dose steroid treatment was initiated for possible chronic immunosuppression caused by her auto-immune condition. She was found to be anemic during this time and laboratory work-up had revealed an elevated ferritin level of 6275 ng/ml. As very few diseases cause an elevated ferritin level, HLH was suspected in the differential. For this, a fibrinogen level was measured and was found to be elevated at 426 mg/dl with a normal serum triglyceride of 153 mg/dl. Her elevated fibrinogen may have been in response to her inflammatory state from her underlying infection. With the persistent febrile episodes, hepatosplenomegaly on examination, persistent pancytopenia, and a suspicion of a hemophagocytic syndrome (HLH), a repeat bone marrow biopsy was performed. Biopsy results now demonstrated normocellular marrow for her age, with increased number of histiocytes with hemophagocytosis identified. There was no evidence of overt myelodysplasia, increase in myeloblasts, plasma cell dyscrasia, or lymphoma. Histiocytes were also highlighted by immunohistochemical stain for CD68 and demonstrated to have been engulfing erythroid cells. Flow cytometry on the aspirate showed no abnormal myeloid maturation, increase in blasts, or clonal population. Cytogenetics was also found to be normal (Figure 3). With these findings, our patient met 5 out of 8 criteria required for the diagnosis of HLH. This included: persistent fevers, hepatosplenomegaly, hyperferritinemia, pancytopenia, and bone marrow demonstration of hemophagocytic cells. Subsequently, she was started on high-dose steroid therapy and she improved modestly. Within 1 week, she once again developed worsening pancytopenia. At this point, she was given intravenous cyclophosphamide for her diagnosed HLH. Her clinical condition continued to deteriorate despite these aggressive efforts and she could not tolerate any further therapy aside from high-dose steroid. She eventually died from hypoxic respiratory failure with worsening pneumonia, secondary to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa.


Hemophagocytic lymphohistiocytosis in a patient with Goodpasture's syndrome: a rare clinical association.

Basnet A, Cholankeril MR - Am J Case Rep (2014)

H/E stain of bone marrow, demonstrating histiocytes with hemophagocytosis (engulfing erythrocytes indicated by the arrow) and with CD-68 staining positive cells in the insert. (Image courtesy of Dr. Heidi Fish).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4199464&req=5

f3-amjcaserep-15-431: H/E stain of bone marrow, demonstrating histiocytes with hemophagocytosis (engulfing erythrocytes indicated by the arrow) and with CD-68 staining positive cells in the insert. (Image courtesy of Dr. Heidi Fish).
Mentions: Despite normal bone marrow biopsy results, she continued to have pancytopenia. High-dose steroid treatment was initiated for possible chronic immunosuppression caused by her auto-immune condition. She was found to be anemic during this time and laboratory work-up had revealed an elevated ferritin level of 6275 ng/ml. As very few diseases cause an elevated ferritin level, HLH was suspected in the differential. For this, a fibrinogen level was measured and was found to be elevated at 426 mg/dl with a normal serum triglyceride of 153 mg/dl. Her elevated fibrinogen may have been in response to her inflammatory state from her underlying infection. With the persistent febrile episodes, hepatosplenomegaly on examination, persistent pancytopenia, and a suspicion of a hemophagocytic syndrome (HLH), a repeat bone marrow biopsy was performed. Biopsy results now demonstrated normocellular marrow for her age, with increased number of histiocytes with hemophagocytosis identified. There was no evidence of overt myelodysplasia, increase in myeloblasts, plasma cell dyscrasia, or lymphoma. Histiocytes were also highlighted by immunohistochemical stain for CD68 and demonstrated to have been engulfing erythroid cells. Flow cytometry on the aspirate showed no abnormal myeloid maturation, increase in blasts, or clonal population. Cytogenetics was also found to be normal (Figure 3). With these findings, our patient met 5 out of 8 criteria required for the diagnosis of HLH. This included: persistent fevers, hepatosplenomegaly, hyperferritinemia, pancytopenia, and bone marrow demonstration of hemophagocytic cells. Subsequently, she was started on high-dose steroid therapy and she improved modestly. Within 1 week, she once again developed worsening pancytopenia. At this point, she was given intravenous cyclophosphamide for her diagnosed HLH. Her clinical condition continued to deteriorate despite these aggressive efforts and she could not tolerate any further therapy aside from high-dose steroid. She eventually died from hypoxic respiratory failure with worsening pneumonia, secondary to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa.

Bottom Line: This was initially attributed to the immunosuppressive effect of hydroxychloroquine.Here, we present a rare case of Goodpasture's syndrome with overlap and pauci-immune vasculitis, which may have triggered the HLH.This correlation has not been described before in the literature.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Trinitas Regional Medical Center, Seton Hall University of Graduate Medical Education, Elizabeth, USA.

ABSTRACT

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome. HLH can occur in the setting of an autoimmune disease, chronic immunosuppression, malignancy, and infection. We discuss a rare case of a young woman who was diagnosed with Goodpasture's syndrome that was most likely complicated by HLH. To the best of our knowledge, this is the first report of HLH in the setting of this rare autoimmune disease.

Case report: A 31-year-old woman who was diagnosed with Goodpasture's syndrome 7 years prior presented with febrile neutropenia. She was initially receiving treatment with azathioprine and prednisone, which was subsequently switched to hydroxychloroquine. Over time, she had developed polyarthritis and was later diagnosed with MPO-ANCA-positive vasculitides. On this admission, her clinical status deteriorated from persistent pancytopenia. This was initially attributed to the immunosuppressive effect of hydroxychloroquine. A bone marrow biopsy was performed and revealed hypercellular bone marrow without any cytogenetic abnormalities. Due to a prolonged pancytopenia thought to be of autoimmune etiology, treatment with high-dose steroids was initiated. With the persistent febrile episodes, hepatosplenomegaly on examination, and laboratory workup that revealed hyperferritinemia and pancytopenia, HLH syndrome was suspected. A repeat bone marrow biopsy confirmed this diagnosis with the presence of hemophagocytosis, demonstrated by the presence of histiocytes engulfing erythroid cells. She also met 5 of 8 diagnostic criteria, which confirmed the diagnosis of HLH. The patient eventually died despite aggressive treatment with high-dose steroid therapy for her autoimmune disorder, as well intravenous antibiotics and supportive care for her underlying infections.

Conclusions: HLH is a syndrome marked by a hyper-inflammatory state aggravated by specific triggers. To make the diagnosis of HLH, at least 5 of the 8 criteria must be met. Treatment involves suppression of the overwhelming inflammatory response by the use of immunomodulators. The mortality rate can range from 50-90% due to delayed recognition and onset of treatment. Here, we present a rare case of Goodpasture's syndrome with overlap and pauci-immune vasculitis, which may have triggered the HLH. This correlation has not been described before in the literature.

Show MeSH
Related in: MedlinePlus