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Case Report/Case Series |

Demodex Folliculitis Mimicking Acute Graft-vs-Host Disease FREE

Jonathan Cotliar, MD1; Olga Frankfurt, MD2
[+] Author Affiliations
1Departments of Dermatology and Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois
2Division of Hematology-Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois
JAMA Dermatol. 2013;149(12):1407-1409. doi:10.1001/jamadermatol.2013.5891.
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Published online

Importance  Acute graft-vs-host disease (GVHD) typically requires high-dose systemic steroids as first-line treatment. Like drug eruptions, viral exanthema, and toxic erythema of chemotherapy, Demodex folliculitis is a clinical mimicker of acute GVHD and requires nonimmunosuppressive therapy. This case of Demodex folliculitis mimicking acute GVHD highlights the need for skin biopsy in patients who have undergone a stem cell transplant with eruptions on the head and neck.

Observations  A 46-year-old white woman with a history of Fms-like tyrosine kinase 3 acute myeloid leukemia presented to the dermatology clinic with a 5-day history of a nonpruritic eruption on her face and neck 28 days after undergoing a double umbilical cord blood hematopoietic stem cell transplant (HSCT). Findings from the skin biopsy demonstrated a deep dermal lymphocytic infiltrate adjacent to follicular units along with an abundance of Demodex mites noted within the hair follicles consistent with Demodex folliculitis. Oral ivermectin, 12 mg, was given, and the eruption cleared within 24 hours.

Conclusions and Relevance  To our knowledge, this is only the fifth reported case of Demodex folliculitis following HSCT, but the first ever reported to be successfully treated with oral ivermectin. Demodex folliculitis should be added to the differential diagnosis of skin eruptions that arise after HSCT.

Figures in this Article

Acute graft-versus-host disease is the major cause of nonrelapse morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Herein, we describe a case of demodex folliculitis mimicking acute cutaneous graft-vs-host disease.

A 46-year-old white woman with a history of Fms-like tyrosine kinase 3 acute myeloid leukemia presented to the dermatology clinic with a 5-day history of a nonpruritic eruption on her face and neck 28 days after undergoing a double umbilical cord blood hematopoietic stem cell transplant (HSCT) following conditioning with fludarabine, cyclophosphamide, thiotepa, and total-body irradiation. Immunosuppressive medications included mycophenolate mofetil, 750 mg twice daily, and cyclosporine, 200 mg twice daily. There had been no recent change to these medications, and the erythematous eruption was not accompanied by cough, shortness of breath, fevers, nausea, diarrhea, abdominal pain, or rhinorrhea.

The physical examination was notable for findings of patchy and confluent erythema of the face and neck (Figure 1A) without ocular, oral, or genital lesions. The rest of the patient’s skin was clear.

Place holder to copy figure label and caption
Figure 1.
Demodex Folliculitis Mimicking Acute Graft-vs-Host Disease

A, Patient on the day of presentation with erythema of the face and neck. B, Patient 2 weeks after initial presentation following a single dose of oral ivermectin.

Graphic Jump Location

Laboratory evaluation revealed a white blood cell count of 2900/μL (reference range, 3500-10 500/μL), a hemoglobin level of 10.3 g/dL (reference range, 11.6-15.4 g/dL), a platelet count of 53 × 103/μL (reference range, 140 × 103/μL to 390 × 103/μL), and an absolute neutrophil count of 19 000/μL (reference range, 1500-8000/μL). (To convert white blood cell count and neutrophil count to ×109/L, multiply by 0.001; to convert platelet count to ×109/L, multiply by 1.0; to convert hemoglobin to grams per liter, multiply by 10.0.) Results from serum chemical analyses were all within normal range.

Based on the timing of onset, distribution, and morphologic characteristics of the eruption, clinical grade I acute cutaneous graft-vs-host disease (GVHD) was suspected. A skin biopsy performed to confirm this suspicion, however, revealed an unremarkable epidermis with a deep dermal lymphocytic infiltrate adjacent to follicular units along with an abundance of Demodex mites noted within the hair follicles (Figure 2). A diagnosis of Demodex folliculitis was rendered. The patient was given a single oral dose of ivermectin, 12 mg, which resulted in complete resolution of her skin lesions within 24 hours, and her skin remained clear at her follow-up visit 2 weeks later (Figure 1B).

Place holder to copy figure label and caption
Figure 2.
Skin Biopsy of Demodex Folliculitis Mimicking Acute Graft-vs-Host Disease

Skin biopsy demonstrating perifollicular lymphocytic inflammation and Demodex mites within the hair follicle (hematoxylin-eosin, original magnification ×10).

Graphic Jump Location

The role of Demodex mites, regular inhabitants of the human pilosebaceous unit, in the pathogenesis of skin disease is somewhat controversial; argument exists as to whether these parasites comprise normal skin flora and do not directly contribute to the development of inflammatory skin eruptions or whether they can be directly implicated as opportunistic pathogens, able to induce dermatoses of the head and neck with clinical variability.1 The evidence for demodicosis in papulopustular rosacea, granulomatous-like rosacea, and blepharitis is compelling, at least in subsets of patients with these conditions.2 Both the degree of Demodex mite infestation3 and serum immunoreactivity to Demodex-associated proteins4 have been demonstrated in patients with rosacea. Most recently, Demodex mite colonization has been determined to be increased in patients with cancer who are taking epidermal growth factor receptor inhibitors5 as well as in an annular facial eruption in an otherwise healthy female.6

Our case is the fifth reported case of Demodex folliculitis mimicking acute cutaneous GVHD in patients following HSCT. In the 4 cases described herein, all Demodex-associated eruptions were presumed to be acute GVHD as well. Lotze et al7 noted a 42-year-old woman with myelofibrosis who developed confluent erythema of the face and neck on day 24 following a matched unrelated HSCT. Skin biopsy findings showed dense perifollicular inflammation with Demodex mites surrounding the hair follicles. Repeated application of hexachlorocyclohexane lotion was able to clear the eruption over the course of 3 weeks. Aisa et al8 reported 2 female patients with chronic myelogenous leukemia who developed pruritic eruptions on the cheeks and jawline on day 110 after undergoing HSCT. Both eruptions were also presumed to be acute GVHD, but skin biopsy results revealed Demodexfolliculorum. Both patients’ skin cleared in 3 to 4 weeks with topical sulfur. Román-Curto et al9 reported the most recent case of demodicidosis mimicking acute GVHD in a 33-year-old woman with acute lymphoblastic leukemia who developed a desquamative facial eruption on day 197 following a matched unrelated HSCT. Skin biopsy results confirmed the presence of Demodex folliculitis, and the lesions cleared with permethrin, 5% ointment, and the combination of topical and oral metronidazole given over 2 months.

Like the aforementioned cases, the present one highlights the need to perform routine skin biopsies in patients after undergoing HSCT who develop eruptions on the head and neck, even when there is a high suspicion of acute GVHD. While more common mimickers of acute GVHD, such as drug eruptions, viral exanthema, toxic erythema of chemotherapy, drug-induced photosensitivity, or photodermatitis are more routinely misdiagnosed as acute GVHD in this patient population, Demodex-associated folliculitis must also be included in the differential diagnosis. Although the presence of Demodex mites within the epidermis does not always demonstrate pathogenicity, skin scraping with use of potassium hydroxide staining for microscopic examination may have precluded skin biopsy, in this case if a high density of mites was observed. Although ours is the fifth reported case of Demodexfolliculorum in a post-HSCT patient, to our knowledge it is the first to be treated successfully with oral ivermectin. The rapid clearance of lesions in our patient following the single dose of ivermectin suggests that this modality may be more efficacious than the protracted courses of topicals and other oral agents given to patients in the 4 previous cases noted.

Corresponding Author: Jonathan Cotliar, MD, Department of Dermatology, Northwestern University, 676 N St Clair, Ste 1600, Chicago, IL 60611 (j-cotliar@northwestern.edu).

Published Online: October 16, 2013. doi:10.1001/jamadermatol.2013.5891.

Author Contributions: Both authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Cotliar, Frankfurt.

Acquisition of data: Both authors.

Analysis and interpretation of data: Both authors.

Drafting of the manuscript: Both authors.

Critical revision of the manuscript for important intellectual content: Both authors.

Administrative, technical, or material support: Both authors.

Study supervision: Cotliar.

Conflict of Interest Disclosures: Dr Cotliar serves on the advisory board of Therakos Inc and has received honoraria. No other disclosures are reported.

Additional Contributions: We thank Pedram Gerami, MD, and Michael Sidiropoulos, MD, both with the Department of Dermatology, Northwestern University Feinberg School of Medicine, for interpretation of the skin biopsy and taking photographs of the slides, respectively.

Elston  DM.  Demodex mites: facts and controversies. Clin Dermatol. 2010;28(5):502-504.
PubMed   |  Link to Article
Hsu  CK, Hsu  MM, Lee  JY.  Demodicosis: a clinicopathological study. J Am Acad Dermatol. 2009;60(3):453-462.
PubMed   |  Link to Article
Zhao  YE, Wu  LP, Peng  Y, Cheng  H.  Retrospective analysis of the association between Demodex infestation and rosacea. Arch Dermatol. 2010;146(8):896-902.
PubMed
O’Reilly  N, Menezes  N, Kavanagh  K.  Positive correlation between serum immunoreactivity to Demodex-associated Bacillus proteins and erythematotelangiectatic rosacea. Br J Dermatol. 2012;167(5):1032-1036.
PubMed   |  Link to Article
Gerber  PA, Kukova  G, Buhren  BA, Homey  B.  Density of Demodexfolliculorum in patients receiving epidermal growth factor receptor inhibitors. Dermatology. 2011;222(2):144-147.
PubMed   |  Link to Article
Martinez-Diaz  GJ, Clark  KM, Vasquez  JG, English  JC  III.  Facial erythematous annular plaques: a case of annular Demodex facial dermatitis? J Am Acad Dermatol. 2012;67(6):e268-e269.
PubMed   |  Link to Article
Lotze  C, Krüger  WH, Kiefer  T,  et al.  Facial rash mimicking cutaneous acute graft-versus-host disease after allogeneic stem cell transplantation for osteomyelofibrosis: was Demodex the culprit? Bone Marrow Transplant. 2006;37(7):711-712.
PubMed   |  Link to Article
Aisa  Y, Mori  T, Tanikawa  A,  et al.  Demodicidosis as a cause of facial eruption developing early after allogeneic hematopoietic stem cell transplantation. Transpl Int. 2008;21(12):1192-1193.
PubMed   |  Link to Article
Román-Curto  C, Meseguer-Yebra  C, Cañueto  J,  et al.  Demodicidosis simulating acute graft-versus-host disease after allogeneic stem cell transplantation in one patient with acute lymphoblastic leukemia. Transpl Infect Dis. 2012;14(4):387-390.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.
Demodex Folliculitis Mimicking Acute Graft-vs-Host Disease

A, Patient on the day of presentation with erythema of the face and neck. B, Patient 2 weeks after initial presentation following a single dose of oral ivermectin.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Skin Biopsy of Demodex Folliculitis Mimicking Acute Graft-vs-Host Disease

Skin biopsy demonstrating perifollicular lymphocytic inflammation and Demodex mites within the hair follicle (hematoxylin-eosin, original magnification ×10).

Graphic Jump Location

Tables

References

Elston  DM.  Demodex mites: facts and controversies. Clin Dermatol. 2010;28(5):502-504.
PubMed   |  Link to Article
Hsu  CK, Hsu  MM, Lee  JY.  Demodicosis: a clinicopathological study. J Am Acad Dermatol. 2009;60(3):453-462.
PubMed   |  Link to Article
Zhao  YE, Wu  LP, Peng  Y, Cheng  H.  Retrospective analysis of the association between Demodex infestation and rosacea. Arch Dermatol. 2010;146(8):896-902.
PubMed
O’Reilly  N, Menezes  N, Kavanagh  K.  Positive correlation between serum immunoreactivity to Demodex-associated Bacillus proteins and erythematotelangiectatic rosacea. Br J Dermatol. 2012;167(5):1032-1036.
PubMed   |  Link to Article
Gerber  PA, Kukova  G, Buhren  BA, Homey  B.  Density of Demodexfolliculorum in patients receiving epidermal growth factor receptor inhibitors. Dermatology. 2011;222(2):144-147.
PubMed   |  Link to Article
Martinez-Diaz  GJ, Clark  KM, Vasquez  JG, English  JC  III.  Facial erythematous annular plaques: a case of annular Demodex facial dermatitis? J Am Acad Dermatol. 2012;67(6):e268-e269.
PubMed   |  Link to Article
Lotze  C, Krüger  WH, Kiefer  T,  et al.  Facial rash mimicking cutaneous acute graft-versus-host disease after allogeneic stem cell transplantation for osteomyelofibrosis: was Demodex the culprit? Bone Marrow Transplant. 2006;37(7):711-712.
PubMed   |  Link to Article
Aisa  Y, Mori  T, Tanikawa  A,  et al.  Demodicidosis as a cause of facial eruption developing early after allogeneic hematopoietic stem cell transplantation. Transpl Int. 2008;21(12):1192-1193.
PubMed   |  Link to Article
Román-Curto  C, Meseguer-Yebra  C, Cañueto  J,  et al.  Demodicidosis simulating acute graft-versus-host disease after allogeneic stem cell transplantation in one patient with acute lymphoblastic leukemia. Transpl Infect Dis. 2012;14(4):387-390.
PubMed   |  Link to Article

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