Iron Screening in Alopecia Areata Patients May Catch Hereditary Hemochromatosis Early
Hereditary hemochromatosis (HHC), a disorder of iron overload, presents with clinical phenotypic heterogeneity. Complications can be mitigated with early intervention. The association between HHC and alopecia areata (AA) is unknown. We report 4 patients with HHC concurrent with AA. In 2 patients, the HHC diagnosis was revealed from the results of laboratory iron studies as part of an alopecia consultation workup. Alopecia areata may be a rare early cutaneous manifestation of HHC in individuals with a predisposition for autoimmunity; however, the genetic relationship between the 2 disorders is currently unknown. Patients at high risk for HHC such as those with a family history and/or those who fit the demographic profile may benefit from laboratory iron screening if they present to the clinic with AA.
Practice Points
- Hereditary hemochromatosis (HHC) is a disorder of iron overload that presents with clinical phenotypic heterogeneity. Complications can be mitigated with early intervention.
- Alopecia areata (AA) may be a rare early cutaneous manifestation of HHC in individuals with a predisposition for autoimmunity; therefore, it is important to evaluate iron status as part of the AA workup.
Patient 2—A 55-year-old White man was referred for evaluation and treatment of alopecia universalis. He had a medical history of skin cancer and vitiligo. He attempted contact immunotherapy with diphenylcyclopropenone scalp treatment but stopped due to intolerable inflammation. Intervention with a topical steroid and topical minoxidil was unsuccessful, but use of triamcinolone acetonide steroid injection on the scalp and topical bimatoprost 0.03% on the eyebrows produced satisfactory results.
The patient’s alopecia workup revealed a ferritin level of 422 ng/mL (reference range, 30–400 ng/mL), which prompted a hematology consultation for further evaluation. Notably, the patient ate red meat several times a week, used iron skillets, and denied receiving blood transfusions. His social habits included 3 alcoholic beverages a night, 5 days a week. Ultrasonography of the liver was recommended to assess potential damage from iron overload and alcohol consumption; the results suggested chronic liver disease, not definitive for cirrhosis, and no evidence of hepatocellular carcinoma. Genetic analysis later revealed the heterozygous H63D variant; therapeutic phlebotomy was recommended.
Patient 3—A 22-year-old White man presented with AA involving his facial beard. He had a medical history of vitiligo and psoriasis and a family history of AA as well as other autoimmune diseases including Hashimoto thyroiditis, psoriasis, eczema, and autoimmune hepatitis. Diphenylcyclopropenone treatment was not successful.
Laboratory studies revealed mildly elevated transaminase and ferritin levels. The patient also presented to the gastroenterologist for evaluation of abdominal pain. Subsequent hematology evaluation confirmed the presence of compound heterozygous C282Y and H63D mutations in the HFE gene, and the patient’s mother was later determined to be homozygous for the C282Y mutation with no elevated ferritin level. The patient’s ferritin level at diagnosis was approximately 500 ng/mL (reference range, 22–322 ng/mL); he required a modest number of therapeutic phlebotomies to normalize his ferritin level.
Patient 4—A 62-year-old White woman presented for evaluation and treatment of patchy hair loss on the scalp of 7 months’ duration. She was subsequently diagnosed with AA. After unsuccessful treatment with a triamcinolone acetonide steroid injection, topical immunotherapy with diphenylcyclopropenone was recommended. The patient achieved full hair regrowth after 35 treatments administered at 3-week intervals.
The patient had a medical history of HHC, including homozygosity for the C282Y mutation, and a family history of HHC in 1 sister. Treatment was therapeutic phlebotomy.
Comment
HHC in the Setting of AA—We presented 4 White patients with both HHC and AA. A PubMed search of articles indexed for MEDLINE using the terms HHC and AA yielded only 1 other reported case of newly identified HHC in a 56-year-old man who presented with pigmented purpuric dermatitis and AA that affected the beard.10 Because HHC is the most common genetic disorder identified in White individuals and has a varied clinical presentation, the documentation of AA may be an important cutaneous clue to help clinicians diagnose HHC early.
Iron Overload in Patients With HHC—The genetic association between HHC and AA, if any, is unknown. What is known is that iron overload can catalyze reactive oxygen species, which can overwhelm cellular antioxidant capacities at particular levels and cause injury to its constituents.11 Data show that the levels of oxidative stress are elevated in the scalp of patients with AA compared to controls and increased 2-fold during the early phase of disease vs late-phase disease.12 Thus, it is possible that increased iron levels in HHC may contribute to AA in genetically susceptible individuals by direct toxicity that ultimately results in the AA hair disorder that is CD8+ T-cell mediated.
Data show that 78% (31/40) of men and 36% (14/39) of women identified with homozygous C282Y mutations determined from family genetic analyses exhibited iron overload.13 In general, a normal life expectancy is possible for patients promptly treated with appropriate therapeutic phlebotomies.14 Thus, early diagnosis and appropriate therapy can prevent consequences of iron overload, which include cirrhosis, diabetes mellitus, and cardiomyopathy.13Iron Screening in the Alopecia Workup—Our cases illustrate how iron screening tests as part of the alopecia workup identified a cohort of White patients with iron overload and subsequently led to an early diagnosis of HHC. The calculated 2% lifetime risk for developing AA highlights the importance of evaluating iron status as part of the AA workup, particularly for White men, and the potential health benefit from early diagnosis of HHC. Limitations of this case series included its retrospective nature and small patient number.
