Thyroid and Adrenal Dysfunction in Hemoglobinopathies Before and After Allogeneic Hematopoietic Cell Transplant.

Purpose: To determine the rate and clinical characteristics associated with abnormal thyroid and adrenal function in recipients of nonmyeloablative hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) and beta-thalassemia. Methods: We retrospectively reviewed patients who enrolled in 4 nonmyeloablative HCT regimens with alemtuzumab and total body irradiation (TBI). Baseline and annual post-HCT data were compared, which included age, sex, sickle phenotype, thyroid panel (total T3, free T4, thyroid stimulating hormone, antithyroid antibodies), cortisol level, ACTH stimulation testing, ferritin, medications, and other relevant medical history. Results: Among 43 patients in haploidentical transplant and 84 patients in the matched related donor protocols with mostly SCD, the rate of any thyroid disorder pre-HCT was 3.1% (all subclinical hypothyroidism) and post-HCT was 29% (10 hypothyroidism, 4 Grave's disease, and 22 subclinical hypothyroidism). Ninety-two (72%) patients had ferritin >1000 ng/dL, of which 33 patients (35.8%) had thyroid dysfunction. Iron overload was noted in 6 of 10 patients with hypothyroidism and 12 of 22 patients with subclinical hypothyroidism.Sixty-one percent were on narcotics for pain control. With respect to adrenal insufficiency (AI) pre-HCT, 2 patients were maintained on corticosteroids for underlying rheumatologic disorder and 8 had AI diagnosed during pre-HCT ACTH stimulation testing (total 10, 7.9%). Post-HCT, an additional 4 (3%) developed AI from corticosteroid use for acute graft vs host disease, Evans syndrome, or hemolytic anemia. Conclusion: Although iron overload was common in SCD, thyroid dysfunction pre-HCT related to excess iron was less common. Exposure to alemtuzumab or TBI increased the rates of thyroid dysfunction post-HCT. In contrast, AI was more common pre-HCT, but no risk factor was identified. AI post-HCT was infrequent and associated with corticosteroid use for HCT-related complications.

Nodular amyloidosis presenting like a primary scarring alopecia.

Nodular amyloidosis (NA) is a rare type of primary localized cutaneous amyloidosis in which light chain amyloid deposits in the skin without concurrent systemic involvement. We report a challenging case of NA on the scalp, mimicking primary scarring alopecia, in a relatively young and healthy 36-year-old man. In addition to a nonspecific clinical appearance with a broad differential, NA can be a difficult diagnosis because it may require ancillary testing, such as liquid chromatography-tandem mass spectrometry to type the amyloid protein, and hematology-oncology workup to exclude systemic disease. Pathologists can highlight the importance of systemic evaluation in their reports to ensure patients receive appropriate management.

Increased Rates of Rhabdomyolysis in Male Hematopoietic Cell Transplantation Recipients Taking Sirolimus and Trimethoprim/Sulfamethoxazole.

Hematopoietic cell transplantation (HCT) offers long-term cure against early morbidity and mortality of hemoglobinopathies, such as sickle cell disease (SCD) and beta-thalassemia. Following HCT, sirolimus is an immunosuppressant used to prevent graft-versus-host disease (GVHD) while receiving trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jirovecii prophylaxis and other antimicrobial agents (including acyclovir). One rare adverse event associated with both drugs is rhabdomyolysis, defined as creatine kinase (CK) elevation at least 5 to 10 times the upper limit of normal. This study was conducted to evaluate the rate of and risk factors for developing rhabdomyolysis in the post-HCT setting. Across 4 haploidentical and matched related donor (MRD) nonmyeloablative protocols, CK levels were prospectively monitored and patients were retrospectively identified for rhabdomyolysis. The rhabdomyolysis was graded based on the severity of CK elevation and other organ injury. At diagnosis, patients were queried for concurrent medication use (ie, sirolimus, TMP-SMX, acyclovir, or statins), sex, age, donor genotype, and time from transplantation. Among 127 patients with mostly SCD, rhabdomyolysis occurred in 22 (17%), including 2 recipients of haploidentical donor HCT and 20 recipients of MRD HCT. The time to the development of rhabdomyolysis was 61 and 73 days for the 2 recipients of haploidentical HCT and a median of 73 days for the MRD HCT recipients. Among the 22 patients who developed rhabdomyolysis, 20 (91%) were receiving sirolimus (2 haploidentical HCT recipients and 18 MRD HCT recipients), and 14 (64%) were also receiving TMP-SMX (all in the MRD HCT group). Seventy-five percent of the haploidentical donors and 69% of the MRDs had sickle cell trait. All but 2 patients with rhabdomyolysis were male. No patients who developed rhabdomyolysis were receiving statins at any point. Higher-than-expected rates of rhabdomyolysis were found post-transplantation for patients with SCD and beta-thalassemia. Contributing risk factors included immunosuppression with sirolimus, TMP-SMX, male sex, and sickle trait donor. These factors differ from the excessive muscle strain or injury, seizures, infections, or HMG-CoA inhibitors typically identified in non-HCT recipients.

Erythrodermic Psoriasis Causing Uric Acid Crystal Nephropathy.

BACKGROUND: Erythrodermic psoriasis is a rare and severe variant of psoriasis. It is characterized by widespread skin erythema, scaling, pustules, or exfoliation of more than 75% of the body's surface area. This condition has life-threatening complications to include hemodynamic, metabolic, immunologic, and thermoregulatory disturbances. One metabolic complication, hyperuricemia, occurs from rapid keratinocyte differentiation and infiltration of inflammatory cells into psoriatic lesions. Although renal injury caused by shunting of blood to the skin has been reported, there are no reports of erythrodermic psoriasis causing crystal-induced nephropathy. We present a case of erythrodermic psoriasis and hyperuricemia complicated by uric acid crystal nephropathy. CASE PRESENTATION: A 57-year-old male with long-standing psoriatic arthritis presented with diffuse scaling of his skin. He was being treated with adalimumab, leflunomide, and topical clobetasol, but had recently stopped taking his medications. Physical exam revealed yellow scaling covering his entire body with underlying erythema and tenderness without mucosal involvement. Labs were notable for a creatinine of 3.3 mg/dL, with no prior history of renal disease, and uric acid of 12.7 mg/dL. He was admitted to the intensive care unit given >80% of body surface area involvement and acute renal failure. Despite aggressive fluid resuscitation, renal function did not improve, and creatinine peaked at 4.61 mg/dL. Urine microscopy showed diffuse polymorphic uric acid crystals, consistent with uric acid crystal-induced nephropathy. He was started on rasburicase, urinary alkalinization, and fluids. His renal function improved dramatically; urine output, uric acid, and electrolytes normalized. He was discharged on topical clobetasol and leflunomide and started on secukinumab with little to no skin involvement. CONCLUSION: This case presents the rare complication of crystal-induced nephropathy in a patient with erythrodermic psoriasis. Uric acid crystal nephropathy is well described in diseases with rapid cell turnover such as tumor lysis syndrome. It is thought that rapid keratinocyte differentiation and inflammatory infiltration of psoriatic lesions produced life-threatening electrolyte abnormalities similar to tumor lysis syndrome. Early recognition of this rare complication is critical, and aggressive fluid resuscitation, urine alkalinization, and uric acid lowering agents should be administered immediately.

Metronidazole caused profound drug-induced immune thrombocytopenia.

Metronidazole is commonly prescribed and has not been known to cause drug-induced immune thrombocytopenia. We have provided clinical and laboratory evidence with DDabs that metronidazole can cause drug-induced immune thrombocytopenia (DITP). Providers must be aware of metronidazole causing DITP because recognition of thrombocytopenia is critical and cessation of the drug should occur promptly.

Next-Generation Gene Sequencing Differentiates Hypoplastic Myelodysplastic Syndrome from Aplastic Anemia.

Hypoplastic Myelodysplastic Syndrome (h-MDS) comprises 15% of all MDS and has traditionally been difficult to distinguish from aplastic anemia (AA) by current testing. Accurate differentiation is important because treatment and prognosis differ. Since the publication of the 2008 World Health Organization classification of MDS, next-generation DNA sequencing has discovered novel mutations strongly associated with AA and MDS. Recent research supports the utility of identifying these mutations in the diagnosis and management of MDS; however, use of next-generation sequencing is not yet recommended in guidelines and the study is not routinely performed. We present a case where next-generation sequencing performed on a peripheral blood specimen aided the diagnosis and management of a 74-year-old man with h-MDS. This case adds to the growing body of evidence supporting the utility of next-generation DNA sequencing in the evaluation of MDS and h-MDS, particularly when diagnosis remains unclear after standard testing.