CED
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Eosinophilic follicular reaction induced by Demodex folliculorum mite: a different disease from eosinophilic folliculitis ~ oz2 and R. Botella-Estrada2 V. Sabater-Marco,1 B. Escutia-Mun 1
Department of Pathology, University General Hospital, Valencia, Spain; and 2Department of Dermatology, University Hospital La Fe, Valencia, Spain
doi:10.1111/ced.12566
Summary
Eosinophilic folliculitis (EF) is an idiopathic dermatitis included in the spectrum of eosinophilic pustular follicular reactions. Demodex folliculorum has been implicated as contributing to the pathogenesis of human immunodeficiency virus-associated EF, but it has not been described outside this context. We present an immunocompetent 65-year-old white man with a 5-year history of recurrent pruritic erythematous and oedematous lesions on his face, neck and scalp. Histopathologically, an eosinophilic microabcess with Demodex folliculorum mite within a pilosebaceous follicle was seen, and considered the causal agent. There were also accumulations of eosinophil granules on collagen bundles, and flame figure formations in the dermis. We believe that ‘eosinophilic follicular reaction’ is an appropriate term to describe this case of EF induced by D. folliculorum and thus distinguish it from the idiopathic form of EF. Moreover, this case suggests that D. folliculorum can sometimes induce an eosinophilic immune reaction.
Eosinophilic folliculitis (EF) is an idiopathic dermatitis first described by Ofuji et al.1 in immunocompetent patients. It is part of the spectrum of eosinophilic pustular follicular reactions. However, there are patients with similar clinical and histopathological findings to EF in which the causative agent has been demonstrated. This context raises issues about the proper terminology for this condition.
Report A 65-year-old white man presented with a 5-year history of a recurrent pruritic eruption involving his face, neck and scalp. On physical examination, erythematous and oedematous plaques of different sizes were seen on the patient’s temple, cheek and retroauricular area (Fig. 1a). There were also erythematous follicular Correspondence: Dr Vicente Sabater-Marco, Department of Pathology, University General Hospital, Avenida Tres Cruces s/n, 46014, Valencia, Spain E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 30 July 2014
ª 2015 British Association of Dermatologists
papules and some follicular scales on his neck (Fig. 1b), but no pustules were seen. The clinical diagnosis was follicular mucinosis or lupus erythematosus tumidus. Laboratory data were within the normal range. Serum analysis for human immunodeficiency virus (HIV) antibody, antinuclear antibody and extractable nuclear antibody, and anti-DNA and antihistone antibodies were negative. Histopathological examination of a skin biopsy identified a severe inflammatory infiltrate in the superficial dermis, composed of lymphocytes and large numbers of eosinophils. The inflammatory infiltrate was focused around hair follicles, and some showed spongiosis at the level of the isthmus. In the interfollicular dermis, there was accumulation of eosinophil granules on collagen bundles and flame figure formations (Fig. 2a). In one of the histological sections, an eosinophilic microabscess containing a Demodex folliculorum mite was seen inside a pilosebaceous follicle (Fig. 2b). A diagnosis of eosinophilic follicular reaction (EFR) induced by D. folliculorum was made, and the patient was treated with topical corticosteroids and oral indomethacin 25 mg twice daily. After 2 weeks of treatment, the lesions showed clinical improvement, and they had fully resolved a month later.
Clinical and Experimental Dermatology (2015) 40, pp413–415
413
Eosinophilic follicular reaction by Demodex V. Sabater-Marco et al.
(a)
(a)
(b)
(b)
Figure 2 (a) Lymphocytic infiltration of follicular isthmus with
Figure 1 (a) Erythematous and oedematous plaques on the
temple, cheek and retroauricular area; (b) erythematous follicular papules and follicular scales on the neck.
Classic EF or Ofuji disease1 is a rare chronic and relapsing inflammatory disease seen predominantly in East Asian and occasionally in white populations. It is most common in men in the third and fourth decades of life, and it manifests as an eruption of sterile pustules, papules, and circinate or serpiginous plaques on the face, trunk and extremities. In addition, immunosuppression-associated EF and infancy-associated EF are distinguished. The literature is replete with reports of patients having similar clinical and histopathological findings to classic EF. In a 2007 literature review, Sufyan et al.2 reported some cases of EF associated with drug therapy, haematological malignancies and silicone injections. Various infections and infestations have been identified as a cause of EF, including larva migrans and scabies mites.3 Most of these cases have been included in a miscellaneous group, possibly because the designation of EF it does not seem justified.
414
Clinical and Experimental Dermatology (2015) 40, pp413–415
spongiosis. The superficial dermis shows infiltration of lymphocytes and eosinophils next to flame figures (haematoxylin and eosin, original magnification 9 50); (b) Eosinophilic microabscess and Demodex folliculorum mite occupying the follicular infundibulum (haematoxylin and eosin, original magnification 9 200).
‘Eosinophilic pustular follicular reaction’ (EPFR) is a term that was first used by Magro and Crowson in 19944 to describe a condition with the characteristic morphological findings of EF but not exclusive to that entity. EPFR represents an excessive immediate or delayed-type hypersensitivity reaction to varous stimuli. In accordance with this concept, we believe this term is adequate to describe the majority of EF cases with known cause, and to distinguish these from idiopathic or classic EF. D. folliculorum is a mite that resides exclusively in the hair follicle infundibulum. When it is present in excessive numbers or penetrates into the dermis, it triggers a perifollicular inflammatory reaction composed of lymphocytes and histiocytes, often with abundant neutrophils and occasionally with multinucleated histiocytes.5 Demodex mites have been implicated in rosacea, especially the ocular, granulomatous and papulopustular subtypes, as well as in perioral dermatitis, particularly in cases secondary to topical corticosteroid
ª 2015 British Association of Dermatologists
Eosinophilic follicular reaction by Demodex V. Sabater-Marco et al.
use.6 In addition, Demodex has been identified in the lesional skin of patients infected with HIV, contributing to the pathogenesis of this type of EF.7 However, D. folliculorum as an aetiological agent of EFR has not been described in immunocompetent patients. Our patient was an immunocompetent 65-year-old man, who presented with pruritic erythematous and oedematous plaques, as well as follicular scales and papules, with a predilection for seborrhoeic areas of the face. Histopathological examination of a skin biopsy revealed a D. folliculorum mite within a follicular eosinophilic microabscess, and flame figures in the dermis. These findings suggest an exaggerated hypersensitivity reaction to the mite, and the diagnosis of ‘eosinophilic follicular reaction’ seems to describe this condition best. Eosinophilic infiltration with flame figures is a distinctive tissue reaction pattern that may be found in Wells syndrome and other diseases such as eczema, prurigo, insect bite, diffuse erythema, tinea and bullous pemphigoid.8 Histopathologically, the flame figures are characterized by a diffuse eosinophilic infiltration and foci of granular material surrounding collagen bundles in the dermis. They are formed by intense eosinophil degranulation with consequent release of major basic protein, which is a potent cytotoxic mediator of injury to parasites. The pathogenesis in this case of EFR is somewhat similar to that seen in papulopustular rosacea.9 In the first stage, a specific immune defect against Demodex allows the proliferation of the mite in the pilosebaceous follicle. In the second stage, some mites penetrate into the dermis; this could trigger an exaggerated immune response that leads to eosinophilic infiltration with flame figure formation. Demodex folliculitis is an entity frequently encountered in daily dermatology practice. Currently, its diagnosis can be confirmed by techniques that measure the mite density in cutaneous lesions of the face, such as standardized skin surface biopsy and direct microscopic examination.10 In our case, the diagnosis of EFR induced by D. folliculorum was suggested by skin biopsy. This method allowed us to explore the composition of the perifollicular infiltrate and to identify the mite. The treatment of EFR induced by D. folliculorum is based on the use of acaricidal drugs. Ivermectin is a synthetic broad-spectrum antiparasitic that has been used in a patient infected with HIV, improving the reaction.7 In our patient’s case, owing to the presence of morphological changes in the dermis suggesting a delayed hypersensitivity reaction, we decided to treat him with topical corticosteroids and oral indomethacin, which resulted in disappearance of the lesions.
ª 2015 British Association of Dermatologists
In conclusion, D. folliculorum mite may manifest clinically and histopathologically as an EF; however, the condition is actually EFR.
Learning points EFR is an adequate term to describe EF cases
with known cause and to distinguish them from idiopathic or classic EF. D. folliculorum is an intradermal parasite that thrives in the human pilosebaceous follicle. It is involved in rosacea and exceptionally may be the causal agent of EFR. In EFR induced by D. folliculorum, eosinophilic infiltration with flame figure formation in the dermis suggests an exaggerated immune response against the mite.
References 1 Ofuji S, Ogino A, Horio T et al. Eosinophilic pustular folliculitis. Acta Derm Venereol 1970; 50: 195–203. 2 Sufyan W, Tan KB, Wong ST, Lee YS. Eosinophilic pustular folliculitis. Arch Pathol Lab Med 2007; 131: 1598–601. 3 Opie KM, Heenan PJ, Delaney TA, Rohr JB. Two cases of eosinophilic pustular folliculitis associated with parasitic infestations. Australas J Dermatol 2003; 44: 217–19. 4 Magro CM, Crowson AN. Eosinophilic pustular follicular reaction: a paradigma of immune dysregulation. Int J Dermatol 1994; 33: 172–8. 5 Hsu CK, Hsu MM, Lee JY. Demodicosis: a clinicopathological study. J Am Acad Dermatol 2009; 60: 453–62. 6 Bonnar E, Eustace P, Powell FC. The Demodex mite population in rosacea. J Am Acad Dermatol 1993; 28: 443–8. 7 Nara T, Katoh N, Inoue K et al. Eosinophilic folliculitis with a Demodex folliculorum infestation successfully treated with ivermectin in a man infected with human immunodeficiency virus. Clin Exp Dermatol 2009; 34: e981–3. 8 Wood C, Miller AC, Jacobs A et al. Eosinophilic infiltration with flame figures. A distinctive tissue reaction seen in Wells’ syndrome and other diseases. Am J Dermatopathol 1986; 8: 186–93. 9 Forton FM. Papulopustular rosacea, skin immunity and Demodex: pityriasis folliculorum as a missing link. J Eur Acad Dermatol Venereol 2012; 26: 19–28. 10 Askin U, Seckin D. Comparison of the two techniques for measurement of the density of Demodex folliculorum: standardized skin surface biopsy and direct microscopic examination. Br J Dermatol 2010; 162: 1124–6.
Clinical and Experimental Dermatology (2015) 40, pp413–415
415
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
Eosinophilic follicular reaction induced by Demodex folliculorum mite: a different disease from eosinophilic folliculitis ~ oz2 and R. Botella-Estrada2 V. Sabater-Marco,1 B. Escutia-Mun 1
Department of Pathology, University General Hospital, Valencia, Spain; and 2Department of Dermatology, University Hospital La Fe, Valencia, Spain
doi:10.1111/ced.12566
Summary
Eosinophilic folliculitis (EF) is an idiopathic dermatitis included in the spectrum of eosinophilic pustular follicular reactions. Demodex folliculorum has been implicated as contributing to the pathogenesis of human immunodeficiency virus-associated EF, but it has not been described outside this context. We present an immunocompetent 65-year-old white man with a 5-year history of recurrent pruritic erythematous and oedematous lesions on his face, neck and scalp. Histopathologically, an eosinophilic microabcess with Demodex folliculorum mite within a pilosebaceous follicle was seen, and considered the causal agent. There were also accumulations of eosinophil granules on collagen bundles, and flame figure formations in the dermis. We believe that ‘eosinophilic follicular reaction’ is an appropriate term to describe this case of EF induced by D. folliculorum and thus distinguish it from the idiopathic form of EF. Moreover, this case suggests that D. folliculorum can sometimes induce an eosinophilic immune reaction.
Eosinophilic folliculitis (EF) is an idiopathic dermatitis first described by Ofuji et al.1 in immunocompetent patients. It is part of the spectrum of eosinophilic pustular follicular reactions. However, there are patients with similar clinical and histopathological findings to EF in which the causative agent has been demonstrated. This context raises issues about the proper terminology for this condition.
Report A 65-year-old white man presented with a 5-year history of a recurrent pruritic eruption involving his face, neck and scalp. On physical examination, erythematous and oedematous plaques of different sizes were seen on the patient’s temple, cheek and retroauricular area (Fig. 1a). There were also erythematous follicular Correspondence: Dr Vicente Sabater-Marco, Department of Pathology, University General Hospital, Avenida Tres Cruces s/n, 46014, Valencia, Spain E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 30 July 2014
ª 2015 British Association of Dermatologists
papules and some follicular scales on his neck (Fig. 1b), but no pustules were seen. The clinical diagnosis was follicular mucinosis or lupus erythematosus tumidus. Laboratory data were within the normal range. Serum analysis for human immunodeficiency virus (HIV) antibody, antinuclear antibody and extractable nuclear antibody, and anti-DNA and antihistone antibodies were negative. Histopathological examination of a skin biopsy identified a severe inflammatory infiltrate in the superficial dermis, composed of lymphocytes and large numbers of eosinophils. The inflammatory infiltrate was focused around hair follicles, and some showed spongiosis at the level of the isthmus. In the interfollicular dermis, there was accumulation of eosinophil granules on collagen bundles and flame figure formations (Fig. 2a). In one of the histological sections, an eosinophilic microabscess containing a Demodex folliculorum mite was seen inside a pilosebaceous follicle (Fig. 2b). A diagnosis of eosinophilic follicular reaction (EFR) induced by D. folliculorum was made, and the patient was treated with topical corticosteroids and oral indomethacin 25 mg twice daily. After 2 weeks of treatment, the lesions showed clinical improvement, and they had fully resolved a month later.
Clinical and Experimental Dermatology (2015) 40, pp413–415
413
Eosinophilic follicular reaction by Demodex V. Sabater-Marco et al.
(a)
(a)
(b)
(b)
Figure 2 (a) Lymphocytic infiltration of follicular isthmus with
Figure 1 (a) Erythematous and oedematous plaques on the
temple, cheek and retroauricular area; (b) erythematous follicular papules and follicular scales on the neck.
Classic EF or Ofuji disease1 is a rare chronic and relapsing inflammatory disease seen predominantly in East Asian and occasionally in white populations. It is most common in men in the third and fourth decades of life, and it manifests as an eruption of sterile pustules, papules, and circinate or serpiginous plaques on the face, trunk and extremities. In addition, immunosuppression-associated EF and infancy-associated EF are distinguished. The literature is replete with reports of patients having similar clinical and histopathological findings to classic EF. In a 2007 literature review, Sufyan et al.2 reported some cases of EF associated with drug therapy, haematological malignancies and silicone injections. Various infections and infestations have been identified as a cause of EF, including larva migrans and scabies mites.3 Most of these cases have been included in a miscellaneous group, possibly because the designation of EF it does not seem justified.
414
Clinical and Experimental Dermatology (2015) 40, pp413–415
spongiosis. The superficial dermis shows infiltration of lymphocytes and eosinophils next to flame figures (haematoxylin and eosin, original magnification 9 50); (b) Eosinophilic microabscess and Demodex folliculorum mite occupying the follicular infundibulum (haematoxylin and eosin, original magnification 9 200).
‘Eosinophilic pustular follicular reaction’ (EPFR) is a term that was first used by Magro and Crowson in 19944 to describe a condition with the characteristic morphological findings of EF but not exclusive to that entity. EPFR represents an excessive immediate or delayed-type hypersensitivity reaction to varous stimuli. In accordance with this concept, we believe this term is adequate to describe the majority of EF cases with known cause, and to distinguish these from idiopathic or classic EF. D. folliculorum is a mite that resides exclusively in the hair follicle infundibulum. When it is present in excessive numbers or penetrates into the dermis, it triggers a perifollicular inflammatory reaction composed of lymphocytes and histiocytes, often with abundant neutrophils and occasionally with multinucleated histiocytes.5 Demodex mites have been implicated in rosacea, especially the ocular, granulomatous and papulopustular subtypes, as well as in perioral dermatitis, particularly in cases secondary to topical corticosteroid
ª 2015 British Association of Dermatologists
Eosinophilic follicular reaction by Demodex V. Sabater-Marco et al.
use.6 In addition, Demodex has been identified in the lesional skin of patients infected with HIV, contributing to the pathogenesis of this type of EF.7 However, D. folliculorum as an aetiological agent of EFR has not been described in immunocompetent patients. Our patient was an immunocompetent 65-year-old man, who presented with pruritic erythematous and oedematous plaques, as well as follicular scales and papules, with a predilection for seborrhoeic areas of the face. Histopathological examination of a skin biopsy revealed a D. folliculorum mite within a follicular eosinophilic microabscess, and flame figures in the dermis. These findings suggest an exaggerated hypersensitivity reaction to the mite, and the diagnosis of ‘eosinophilic follicular reaction’ seems to describe this condition best. Eosinophilic infiltration with flame figures is a distinctive tissue reaction pattern that may be found in Wells syndrome and other diseases such as eczema, prurigo, insect bite, diffuse erythema, tinea and bullous pemphigoid.8 Histopathologically, the flame figures are characterized by a diffuse eosinophilic infiltration and foci of granular material surrounding collagen bundles in the dermis. They are formed by intense eosinophil degranulation with consequent release of major basic protein, which is a potent cytotoxic mediator of injury to parasites. The pathogenesis in this case of EFR is somewhat similar to that seen in papulopustular rosacea.9 In the first stage, a specific immune defect against Demodex allows the proliferation of the mite in the pilosebaceous follicle. In the second stage, some mites penetrate into the dermis; this could trigger an exaggerated immune response that leads to eosinophilic infiltration with flame figure formation. Demodex folliculitis is an entity frequently encountered in daily dermatology practice. Currently, its diagnosis can be confirmed by techniques that measure the mite density in cutaneous lesions of the face, such as standardized skin surface biopsy and direct microscopic examination.10 In our case, the diagnosis of EFR induced by D. folliculorum was suggested by skin biopsy. This method allowed us to explore the composition of the perifollicular infiltrate and to identify the mite. The treatment of EFR induced by D. folliculorum is based on the use of acaricidal drugs. Ivermectin is a synthetic broad-spectrum antiparasitic that has been used in a patient infected with HIV, improving the reaction.7 In our patient’s case, owing to the presence of morphological changes in the dermis suggesting a delayed hypersensitivity reaction, we decided to treat him with topical corticosteroids and oral indomethacin, which resulted in disappearance of the lesions.
ª 2015 British Association of Dermatologists
In conclusion, D. folliculorum mite may manifest clinically and histopathologically as an EF; however, the condition is actually EFR.
Learning points EFR is an adequate term to describe EF cases
with known cause and to distinguish them from idiopathic or classic EF. D. folliculorum is an intradermal parasite that thrives in the human pilosebaceous follicle. It is involved in rosacea and exceptionally may be the causal agent of EFR. In EFR induced by D. folliculorum, eosinophilic infiltration with flame figure formation in the dermis suggests an exaggerated immune response against the mite.
References 1 Ofuji S, Ogino A, Horio T et al. Eosinophilic pustular folliculitis. Acta Derm Venereol 1970; 50: 195–203. 2 Sufyan W, Tan KB, Wong ST, Lee YS. Eosinophilic pustular folliculitis. Arch Pathol Lab Med 2007; 131: 1598–601. 3 Opie KM, Heenan PJ, Delaney TA, Rohr JB. Two cases of eosinophilic pustular folliculitis associated with parasitic infestations. Australas J Dermatol 2003; 44: 217–19. 4 Magro CM, Crowson AN. Eosinophilic pustular follicular reaction: a paradigma of immune dysregulation. Int J Dermatol 1994; 33: 172–8. 5 Hsu CK, Hsu MM, Lee JY. Demodicosis: a clinicopathological study. J Am Acad Dermatol 2009; 60: 453–62. 6 Bonnar E, Eustace P, Powell FC. The Demodex mite population in rosacea. J Am Acad Dermatol 1993; 28: 443–8. 7 Nara T, Katoh N, Inoue K et al. Eosinophilic folliculitis with a Demodex folliculorum infestation successfully treated with ivermectin in a man infected with human immunodeficiency virus. Clin Exp Dermatol 2009; 34: e981–3. 8 Wood C, Miller AC, Jacobs A et al. Eosinophilic infiltration with flame figures. A distinctive tissue reaction seen in Wells’ syndrome and other diseases. Am J Dermatopathol 1986; 8: 186–93. 9 Forton FM. Papulopustular rosacea, skin immunity and Demodex: pityriasis folliculorum as a missing link. J Eur Acad Dermatol Venereol 2012; 26: 19–28. 10 Askin U, Seckin D. Comparison of the two techniques for measurement of the density of Demodex folliculorum: standardized skin surface biopsy and direct microscopic examination. Br J Dermatol 2010; 162: 1124–6.
Clinical and Experimental Dermatology (2015) 40, pp413–415
415
