Hritish lournal of Dermatology (1992) 126, 392-394.
Eosinophilic pustular folliculitis in an HIV-positive man: response to cetirizine D.W.S.HARRIS. L.OSTLERE. C.BUCKLEY. M.JOHNSON* AND M.H.A.RUSTIN Departments of IJermalohmt and 'Thoriicic Medicine, The Royal h'ree Ilospitu! and School of Medicine. Umdon NW i 2Qii. U.K. Accepted for publication 7 November 1991
Summary
Eosinophilic pustular follicuiitis is a rare condition which is bein(i increasingly reported in HIVpositive patients. Many therapies have been used to treat this condition. We report the tirst succe.ssful use of the H| antihistamine cetirizine to treat the condition and postulate that the specific antieosinophilic action of this drug may explain the beneficial clinical effect seen in our patient.
Case report A fi2-year-old homosexual man who was diagnosed HIV-positive in July 1990. presented to the dermatology department in January 1991 with a 2-week history of an itchy eruption affecting the face, particularly the cheeks, lateral aspects of the neck, and the trunk and limbs. He reported that this had been a recurrent problem for the previous i months and had only partially responded to moderately potent topical corticosteroids. Examination revealed multiple 1-2-nim diameter follicular erythematous papules on hair-bearing areas of Ihe face (Fig. 1) and chest. Some of the lesions were pustular and others were in groups. Several displayed an annular configuration with central clearing. The oral mucosa. palms and soles were normal. I'here was no evidence of organomegaiy or lymphadenopathy. Viral, bacterial and fungal cultures of swabs and scrapings from pustules and skin were negative. The haemoglobin was 12-4 g/dl. white cell count 2 9 x l()''/l (neutrt)phils b i% lymphocytes 32% and monocytes 5%) and platelets 282 x lO^'/l. The aspartate transaminase was 47 IJ/I (normal range S-4()) but otherwise the biochemical screen was normal. A biopsy of a lesion on the side of the neck showed an inilammatory infiltrati- composed of eosinophils. tieutrophils and mononudear cells within the tollicular epithelium, sebaceous glands and perifollicular region (Fig. 2). In several areas there was spongiosis. dermal oedema and a perivascular infiltrate containing many eostnophils which extended into the subcutaneous fat. Periodic acid-Schiff and Gram stains were negative. Correspondence: D.W.S.Harris.
392
Figure 1. l-ollicular papulo-pustular eruption over tbe right side of the neck extending on to tbe cheek.
EOSINOPHILIC PUSTULAR FOLLICULITIS
393
Figure 2. Chronic inllaminalory eel! inlHtrate of mainly eosinophils and lymphocytes invading the infunttibulum of the hair follicle, with areas of spongiosis ( x 4001.
The rash was treated with mild and potent topical corticosteroids applied twice daily, and oral tcrfenadine I 20 mg b.d. with no bciieiit. This trcatmL-nt was stopped after 3 weeks and cetirizine U) mg b.d. was commenced in view of the pro po rule ranee of eosinophils in the intlammutory intiltrate and the known effects of this drtig on eosinophils. Improvement in the rash and pnuittis was noticed within 48 h and there was complete resolution within 12 days. In July 1990 he developed pulmonary tuberculosis. In October 1990 he developed a left subnrbital swelling and teslicuhir enlargement and was found to have a high grade B-cell lymphoma. He was initially treated with chemotherapy and later with radiotherapy for CNS relapse. He died from CNS itivolvement in April 1991.
Discussion Eosinophilic pustular foliiculitis was first described in Japanese patients by Ise and Ofuji' in 1965. It is characterized by crops of sterile follicular pustules on erythenialous papules, and typically affects the lace. trunk and proximal extremities. The lesions become Lonlluent. forming indurated plaques with a tendency to central healing. The lesions are pruritic. They are not associated with any systemic upset. A moderate leucocytosis and eosinophilia occurs together with a raised serum IgH in the majority of patients. High titres of circulating IgG and IgM have been found directed to the cytoplasm of the basal cells of the epidermis and the outer root sheath of hair follicles.- Intercellular IgG
deposition has been reported in the lower epidermis from
lesional and non-iesional skin.' although several workers have found no evidence of positivt; immunofluorescence.'*"' Kosinophilic pustular foliiculitis must be differentiated from other pustular conditions of which the most common is a diffuse pustular dermatophytosis. Other differential diagnoses include follicular impetigo, nummular eczema, pustular psoriasis and subcomeal pustular dermatosis. The pathogenesis of Ofuji's disease is unknown. It has been postulated to be a hypersensitivity phenomenon to the house dust mite Dermatophagoitles pteronyssinus or possibly the follicle mite Demodex foUiculorum.'' The propensity for the condition to affect HIV sufferers has been noted.' and it raises the question of whether the immunodeficient state confers exaggerated sensitivity to a skin saprophyte or dermiitophyte. Numerous treatments have been tried in this condition including systemic and topical steroids, dapsone*^ oxyphenbutazone."* indomethacin,'" aspirin, minocycline. colchicine. glycyrrhizin. isotretinoin and UVB phototherapy.' ' This is the first reported used of cetirizine. a new Hi blocking drug in treating the condition. Cetirizine is the major human metabolite of hydroxyzine. being formed by oxidation of the primary alcoholic side-chain to a carboxylic moiety. In addition to conventional antihistamine properties'^ it was noted that cetirizine blocked the migration of eosinophils on to a skin window 24 h after antigen challenge, a phenomenon not explained by 11] blockade.'' Other studies have shown that cetirizine
394
D.W.S.HARRIS et al.
inlluences the pathogenesis of the late-phase reaction by causing a significant reduction in the inflammatory cell intiltrate. both eosinophilic and basophilic components, and in addition profotindly depresses the production of i'CJUj.'^ Administration of cetirizine at therapeutic concentration has been shown lo produce signiHcant inhibition of local eosinophil accumulation in response to compound 48/80.'^ Eosinophil chemotaxis induced by N-f()rmyl-Met-I,eu-Phe (FMLP) and platelet-activating factor (PAl-) is potently inhibited by the drug:'^ there is no evidence to support any PAF receptor-blocking activity."' In conclusion, the inliibitory effect of cetirizine on eosinophil migration appears to be an action independent of its potent anti-H[ effect. We believe that these unique properties may have been responsible for the clinical improvement seen in our patient.
References 1 Ise S. Ofuji S. Subcorneal pustular dermatosis: A follicular variant? Arch Dermatol iyfi5; 92: If)9-71. 2 Nunzi \-.. Parodi A. Rehora A. Ofuji's disease: high circulating titers of Igt; and IgM directed to basal cytopla.sm. / Am Acad Dermatol 1985; 12: 2M-7i. i Vakilzadeh 1-, Suter L, Knop ]. Macher E. Eosinophilic pustulosis with pemphigus-like antibody. Dermatoiogica 1981; 162: 26S-72. 4 Hoist R. Eosinophilif pustular loliiculitis: Report of a iiuropean case. BrJ Dennatol 1976: 95: 661-4.
5 Orfanos CR. Sterry W. Sterile eosinophile Pustulose. Dermatoiogica 1978: 1S7: I9J-2(1S. (i Cutler TP. [ktsinophilic pustular folliculilis. Clin l-^xp Dermatol
1981; 6: 327-32. 7 Soeprono FF. Sehinella RA. Fosinophilic pustular folliculitis in patients with acquired immunodeticiency syndrome. Report of three cases. J Am Acad Dfrmatol 1986; 14: 102(1-2. S Ofuji S. Ogino A. I lorio T el
Eosinophilic pustular folliculitis in an HIV-positive man: response to cetirizine D.W.S.HARRIS. L.OSTLERE. C.BUCKLEY. M.JOHNSON* AND M.H.A.RUSTIN Departments of IJermalohmt and 'Thoriicic Medicine, The Royal h'ree Ilospitu! and School of Medicine. Umdon NW i 2Qii. U.K. Accepted for publication 7 November 1991
Summary
Eosinophilic pustular follicuiitis is a rare condition which is bein(i increasingly reported in HIVpositive patients. Many therapies have been used to treat this condition. We report the tirst succe.ssful use of the H| antihistamine cetirizine to treat the condition and postulate that the specific antieosinophilic action of this drug may explain the beneficial clinical effect seen in our patient.
Case report A fi2-year-old homosexual man who was diagnosed HIV-positive in July 1990. presented to the dermatology department in January 1991 with a 2-week history of an itchy eruption affecting the face, particularly the cheeks, lateral aspects of the neck, and the trunk and limbs. He reported that this had been a recurrent problem for the previous i months and had only partially responded to moderately potent topical corticosteroids. Examination revealed multiple 1-2-nim diameter follicular erythematous papules on hair-bearing areas of Ihe face (Fig. 1) and chest. Some of the lesions were pustular and others were in groups. Several displayed an annular configuration with central clearing. The oral mucosa. palms and soles were normal. I'here was no evidence of organomegaiy or lymphadenopathy. Viral, bacterial and fungal cultures of swabs and scrapings from pustules and skin were negative. The haemoglobin was 12-4 g/dl. white cell count 2 9 x l()''/l (neutrt)phils b i% lymphocytes 32% and monocytes 5%) and platelets 282 x lO^'/l. The aspartate transaminase was 47 IJ/I (normal range S-4()) but otherwise the biochemical screen was normal. A biopsy of a lesion on the side of the neck showed an inilammatory infiltrati- composed of eosinophils. tieutrophils and mononudear cells within the tollicular epithelium, sebaceous glands and perifollicular region (Fig. 2). In several areas there was spongiosis. dermal oedema and a perivascular infiltrate containing many eostnophils which extended into the subcutaneous fat. Periodic acid-Schiff and Gram stains were negative. Correspondence: D.W.S.Harris.
392
Figure 1. l-ollicular papulo-pustular eruption over tbe right side of the neck extending on to tbe cheek.
EOSINOPHILIC PUSTULAR FOLLICULITIS
393
Figure 2. Chronic inllaminalory eel! inlHtrate of mainly eosinophils and lymphocytes invading the infunttibulum of the hair follicle, with areas of spongiosis ( x 4001.
The rash was treated with mild and potent topical corticosteroids applied twice daily, and oral tcrfenadine I 20 mg b.d. with no bciieiit. This trcatmL-nt was stopped after 3 weeks and cetirizine U) mg b.d. was commenced in view of the pro po rule ranee of eosinophils in the intlammutory intiltrate and the known effects of this drtig on eosinophils. Improvement in the rash and pnuittis was noticed within 48 h and there was complete resolution within 12 days. In July 1990 he developed pulmonary tuberculosis. In October 1990 he developed a left subnrbital swelling and teslicuhir enlargement and was found to have a high grade B-cell lymphoma. He was initially treated with chemotherapy and later with radiotherapy for CNS relapse. He died from CNS itivolvement in April 1991.
Discussion Eosinophilic pustular foliiculitis was first described in Japanese patients by Ise and Ofuji' in 1965. It is characterized by crops of sterile follicular pustules on erythenialous papules, and typically affects the lace. trunk and proximal extremities. The lesions become Lonlluent. forming indurated plaques with a tendency to central healing. The lesions are pruritic. They are not associated with any systemic upset. A moderate leucocytosis and eosinophilia occurs together with a raised serum IgH in the majority of patients. High titres of circulating IgG and IgM have been found directed to the cytoplasm of the basal cells of the epidermis and the outer root sheath of hair follicles.- Intercellular IgG
deposition has been reported in the lower epidermis from
lesional and non-iesional skin.' although several workers have found no evidence of positivt; immunofluorescence.'*"' Kosinophilic pustular foliiculitis must be differentiated from other pustular conditions of which the most common is a diffuse pustular dermatophytosis. Other differential diagnoses include follicular impetigo, nummular eczema, pustular psoriasis and subcomeal pustular dermatosis. The pathogenesis of Ofuji's disease is unknown. It has been postulated to be a hypersensitivity phenomenon to the house dust mite Dermatophagoitles pteronyssinus or possibly the follicle mite Demodex foUiculorum.'' The propensity for the condition to affect HIV sufferers has been noted.' and it raises the question of whether the immunodeficient state confers exaggerated sensitivity to a skin saprophyte or dermiitophyte. Numerous treatments have been tried in this condition including systemic and topical steroids, dapsone*^ oxyphenbutazone."* indomethacin,'" aspirin, minocycline. colchicine. glycyrrhizin. isotretinoin and UVB phototherapy.' ' This is the first reported used of cetirizine. a new Hi blocking drug in treating the condition. Cetirizine is the major human metabolite of hydroxyzine. being formed by oxidation of the primary alcoholic side-chain to a carboxylic moiety. In addition to conventional antihistamine properties'^ it was noted that cetirizine blocked the migration of eosinophils on to a skin window 24 h after antigen challenge, a phenomenon not explained by 11] blockade.'' Other studies have shown that cetirizine
394
D.W.S.HARRIS et al.
inlluences the pathogenesis of the late-phase reaction by causing a significant reduction in the inflammatory cell intiltrate. both eosinophilic and basophilic components, and in addition profotindly depresses the production of i'CJUj.'^ Administration of cetirizine at therapeutic concentration has been shown lo produce signiHcant inhibition of local eosinophil accumulation in response to compound 48/80.'^ Eosinophil chemotaxis induced by N-f()rmyl-Met-I,eu-Phe (FMLP) and platelet-activating factor (PAl-) is potently inhibited by the drug:'^ there is no evidence to support any PAF receptor-blocking activity."' In conclusion, the inliibitory effect of cetirizine on eosinophil migration appears to be an action independent of its potent anti-H[ effect. We believe that these unique properties may have been responsible for the clinical improvement seen in our patient.
References 1 Ise S. Ofuji S. Subcorneal pustular dermatosis: A follicular variant? Arch Dermatol iyfi5; 92: If)9-71. 2 Nunzi \-.. Parodi A. Rehora A. Ofuji's disease: high circulating titers of Igt; and IgM directed to basal cytopla.sm. / Am Acad Dermatol 1985; 12: 2M-7i. i Vakilzadeh 1-, Suter L, Knop ]. Macher E. Eosinophilic pustulosis with pemphigus-like antibody. Dermatoiogica 1981; 162: 26S-72. 4 Hoist R. Eosinophilif pustular loliiculitis: Report of a iiuropean case. BrJ Dennatol 1976: 95: 661-4.
5 Orfanos CR. Sterry W. Sterile eosinophile Pustulose. Dermatoiogica 1978: 1S7: I9J-2(1S. (i Cutler TP. [ktsinophilic pustular folliculilis. Clin l-^xp Dermatol
1981; 6: 327-32. 7 Soeprono FF. Sehinella RA. Fosinophilic pustular folliculitis in patients with acquired immunodeticiency syndrome. Report of three cases. J Am Acad Dfrmatol 1986; 14: 102(1-2. S Ofuji S. Ogino A. I lorio T el
