Microcytic Anemia and Celiac Disease Preceding Pulmonary Symptoms in Lane-Hamilton Syndrome

Abstract

History and Case PresentationPatient is a 36 year old white male with a history of chronic microcytic anemia and tobacco use. He could not recall any pertinent family history. His chronic anemia started at age 29, at which time he had no pulmonary symptoms. Representative laboratory studies included HGB 7.7 HCT 27.2 MCV 60.7 FE/TIBC of 13/428 with albumin of 3.2. He was diagnosed with iron deficiency, and received multiple intravenous iron infusions. These therapies briefly increased his hematocrit, however, he consistently required PRBC transfusions within 1-2 months of receiving intravenous iron, as he would again become anemic with microcytosis; he estimated that he had received approximately 30 units of PRBCs since age 29. Dyspnea on exertion was first noticed at age 34, which progressively worsened and was associated with occasional episodes of blood tinged sputum and cough, but never frank hemoptysis. Pulmonary function tests in 2016 were reportedly normal, and there were no abnormalities on CXR.Multiple EGDs and colonoscopies were performed without any evidence of bleeding. Duodenal biopsies with villous flattening were first noted in 2014. Patient adhered to a gluten free diet for two months immediately following his diagnosis of celiac sprue and reported that his anemia stabilized, however he stopped the diet for unclear reasons.He presented to our facility in May of 2017 with intermittent sharp chest pain, severe dyspnea on exertion, and lightheadedness. Initial HGB was 7.2 HCT 24.7 MCV 59.2 WBC 6700 PLT 104000. Iron studies obtained prior to transfusion reveal Fe/TIBC of 17/253, ferritin 90, albumin 1.8. Peripheral smear was consistent with iron deficiency, with mild to moderate anisopoikilocytosis. Absolute reticulocyte count the day after admission was 0.104 with HCT of 21.7.He had a similar presentation 8 months prior, in October 2016. CT chest was remarkable for ground-glass opacities, pulmonary fibrosis, emphysema, and mild bilateral hilar adenopathy. There was nephrotic range proteinuria, and albumin was 1.9. He was given ferric gluconate with improvement in his symptoms, and was discharged four days later with HGB of 9.2. He was lost to follow up until May, and did not receive scheduled EBUS and lung biopsy. Repeat CT scan was performed on second admission, showing interval progression of peripheral fibrosis and honeycombing (Image 1).Investigations in 2017 included an EGD/colonoscopy, with single duodenal biopsy finding of increased intraepithelial lymphocytes, with preserved villous architecture, h. pylori negative. Tissue transglutaminase IgA was >250 U/mL and anti-gliadin IgA was 26 U/mL. Genetic testing revealed HLA DQ2 serotype. There was no evidence of CHF or pulmonary HTN on Echo. Hemoglobin electrophoresis revealed no abnormal hemoglobin migration and physiologic HbA2 and HbF levels. B12 and folate levels were within normal limits. Lung biopsy revealed alveolar filling with numerous hemosiderin laden macrophages, in background of alveolar pneumoconiosis and phlebosclerosis, (image 2, high magnification).He was administered PRBCs and ferric gluconate, and discharged with instructions to initiate gluten-free diet, as well undergo renal biopsy to evaluate nephrotic syndrome.DiscussionLane-Hamilton Syndrome (LHS), the association of Idiopathic Pulmonary Hemosiderosis (IPH), celiac disease, and microcytic anemia is an extremely rare clinical entity with 15 worldwide cases described in adults. When patient presented with microcytic anemia, ferritin was consistently in the normal range, while remaining iron studies including Fe/TIBC and transferrin saturation were consistent with iron deficiency when corrected for proteinuria and transferrin loss. Historic CBC and iron studies revealed a clear iron deficiency pattern as described. Parenteral iron infusion did improve hematocrit on multiple presentations, but response was transient. Celiac disease was proven by biopsy and serology. Hemosiderin deposition was found on lung biopsy without a plausible alternate etiology. These features are consistent with known characteristics of LHS. While iron deficiency resistant to iron supplementation has been described without inital pulmonary findings in children with IPH, to our knowledge, iron deficiency with celiac disease preceding the development of IPH by such a long interval has not heretofore been described in adult LHS. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.