http://informahealthcare.com/jdt ISSN: 0954-6634 (print), 1471-1753 (electronic) J Dermatolog Treat, Early Online: 1–2 ! 2015 Informa UK Ltd. DOI: 10.3109/09546634.2015.1024599
CASE REPORT
Intravenous human immunoglobulin for treatment of folliculitis decalvans Nuriah Ismail, Nicola Ralph, and Gillian Murphy
J Dermatolog Treat Downloaded from informahealthcare.com by Nyu Medical Center on 05/20/15 For personal use only.
Department of Dermatology, Beaumont Hospital, Dublin, Ireland
Abstract
Keywords
We report a case of folliculitis decalvans (FD) successfully treated with intravenous human immunoglobulin (HIG). Many conventional treatments with topical agents and oral antibiotics had failed to achieve disease remission, treatment with HIG at a dose of 2 g/kg for the first month, reduced to 1 g/kg for second to fourth months was therefore started, which resulted in rapid improvement and ultimately complete resolution of FD. Clinical improvement was noted after the first infusion of HIG and remission of inflammation was achieved after the fourth infusion. Disease remission was sustained for six months following the last HIG infusion. The exact mechanism of action of HIG is poorly understood. However, it is thought to act as an immunomodulatory agent by altering different components of immune functions. To our knowledge, this is the first case reported in the literature of FD successfully treated with intravenous HIG.
Cicatricial alopecia, folliculitis decalvans, human immunoglobulin, IVIG, scarring alopecia
Introduction Folliculitis decalvans (FD) is a rare inflammatory disorder predominantly occurring in young and middle-aged adults with a slight preponderance of the male gender. It usually affects the vertex and occipital area of the scalp, with areas of erythema, follicular hyperkeratosis, erosions, crusts and scarring alopecia causing pain, itching and burning sensations on the scalp (1). FD is a highly distressing condition that is usually resistant to many treatments.
Report A 29-year old Caucasian male presented with a six year history of recurrent cicatricial alopecia with purulent and tufted folliculitis at the vertex of the scalp (Figure 1). He had multiple disappointing treatments over the years including topical and oral steroids and long-term oral antibiotics. Dermatological examination revealed no concomitant skin diseases and review of systems was unremarkable for any immunodeficiency diseases. Laboratory investigations of full blood count, renal and liver profile, anti-nuclear antibody, anti-extractable nuclear antigens, complement level, serum protein electrophoresis and immunoglobulins were all within normal range except for marginally low lymphocyte count at 1.3 109/L (normal range 1.5–4.0 109/L). Diagnostic skin punch biopsy was carried out and histology showed follicular and perifollicular rupture with a marked predominantly neutrophilic acute and chronic inflammatory infiltrate in the superficial and mid-dermis. Periodic acid-Schiff (PAS) stain preparation showed no fungal element. A diagnosis
History Received 7 January 2015 Revised 27 January 2015 Accepted 27 January 2015 Published online 23 March 2015
of FD was made. The patient had previously taken a combination of rifampicin and clindamycin, both at a dosage of 300 mg twice daily for three months with no clinical improvement. Repeated swabs on the area showed persistent Staphylococcus aureus growth that was sensitive to all the antibiotics tested. The patient was commenced on oral flucloxacillin at a dose of 500 mg four times a day, despite which he continued to have refractory deep and inflammatory papules, erythema and suppurative patches of alopecia. On the basis of case series of intramuscular use of immunoglobulin (2), the decision was made to commence him on immunoglobulin. We chose the intravenous rather than the intramuscular route as a method of administration of human immunoglobulin (HIG). The reason for this was the intramuscular route can be painful for the patient as reported from the case series (2). The patient was started on monthly infusions of FlebogammaÕ , a HIG which is an off-label treatment for FD at a dose of 2 g per kilogram (g/kg) for the first month, reduced to 1 g/kg for second to fourth months. Concomitant treatment with oral flucloxacillin was discontinued after the third infusion of HIG. Overall, the patient had four infusions with a total dose of 425 g of HIG over this four-month period (patient’s bodyweight 85 kg). The patient started to show clinical improvement after the first infusion of HIG, with less erythema, scaling and suppuration of the affected scalp. He complained of a transient headache after the first high-dose infusion. He had no other side effects of the treatment. Disease remission was noted after the fourth infusion of HIG (Figure 2). The patient continued to use only cicloprox olamine shampoo after the infusion. Complete resolution of FD was sustained for six months after the last infusion of HIG.
Discussion Correspondence: Nuriah Ismail, Department of Dermatology, Beaumont Hospital, Dublin 9, Ireland. Tel: +353 0 18092752. Fax: +353 0 18093370. E-mail: [email protected]
FD is an uncommon neutrophilic inflammation of the scalp characterised by painful, recurrent follicular exudation progressing to primary cicatricial alopecia (1). It was first described by
2
N. Ismail et al.
J Dermatolog Treat Downloaded from informahealthcare.com by Nyu Medical Center on 05/20/15 For personal use only.
Figure 1. Pre-treatment with human immunoglobulin.
J Dermatolog Treat, Early Online: 1–2
It consists primarily of the antibody immunoglobulin G (IgG) with small amounts of IgM, IgA and other serum proteins. HIG can be given via intravenous, subcutaneous or intramuscular route. Literature review of the role of intravenous immunoglobulin in the treatment of FD revealed no previous reports of its use. Goo et al. reported good response of 63 patients treated with intramuscular HIG for recalcitrant suppurative diseases, three of them had a diagnosis of FD (2). HIG has been used in various dermatological diseases, some with very little understanding of its exact pharmacodynamics on the diseases. HIG is thought to act as an immunomodulatory and anti-inflammatory agent by altering different components of immune functions, with innate and adaptive pathways in immune systems being potentially targeted. It was well described in patients with Kawasaki disease for which treatment with HIG led to reduction in inflammatory markers (6). Studies for which many were in vitro or animal models showed decrease in the production of proinflammatory cytokines, the down-regulation of adhesion molecules and the neutralisation of superantigens (7). Generally, the dosage of HIG used to treat autoimmune and inflammatory diseases is four to five times higher than those used in patients with immunodeficiency states (8). HIG is generally well tolerated; with common adverse effects including headache and alteration of blood pressure during infusion. More rare and severe complications including renal failure, thrombosis, pulmonary embolism and stroke have also been reported. In IgA-deficient patients, anaphylaxis has been reported (9). In conclusion, we report a case of FD successfully treated with intravenous HIG. Given the fact that the patient only responded after the HIG was commenced and the improvement was sustained after oral flucloxacillin was discontinued, showed that HIG contributed to the therapeutic effect. We propose larger prospective studies are needed to evaluate the use of HIG in the treatment of FD.
Declaration of interest The authors report no declaration of interest. Figure 2. Post-treatment with human immunoglobulin.
References Quinquaud on case of ‘‘folliculite e´pilante et destructive des regions velues’’ in 1888 (3). Brocq et al. in 1905 later coined the term ‘‘folliculitis decalvans’’ and distinguished it from other types of cicatricial alopecia. The aetiology of FD remains unclear. It was thought to be due to abnormal host response to S. aureus although this remains controversial (4). One hypothesis outlined the role of S. aureus in hair follicles infection causing local inflammation with recruitment of neutrophils and several other pro-inflammatory and profibrotic mediators in perifollicular dermis leading to fibrosis (5). Antimicrobial agents remain the first-line therapy for FD with or without microbiological evidence on the swab culture from these lesions. The disease tends to be chronic and recurrent in the majority of patients and anti-staphylococcal treatments are not always effective. Other treatments used for FD are topical, intralesional and oral steroids, topical antiseptic substances, isotretinoin and dapsone with variable response (1). HIG is a blood product with concentrated antibody-containing solution prepared from plasma obtained from human donors.
1. Otberg N, Kang H, Alzolibani AA, et al. Folliculitis decalvans. Dermatol Ther. 2008;21:238–44. 2. Goo B, Chung HJ, Chung WG, et al. Intramuscular immunoglobulin for recalcitrant suppurative diseases of the skin: a retrospective review of 63 cases. Br J Dermatol. 2007;157:563–8. 3. Quinquaud E. Folliculite e´pilante et destructive des regions values. Bull Mem Soc Hop Paris. 1888;5:395–8. 4. Powell JJ, Dawber RPR, Gatter K. Folliculitis decalvans including tufted folliculitis: clinical, histological and therapeutic findings. Br J Dermatol. 1999;140:328–33. 5. Chiarini C, Torchia D, Bianchi B, et al. Immunopathogenesis of folliculitis decalvans. Clues in early lesions. Am J Clin Pathol. 2008; 130:526–34. 6. Laxer RM, Schaffer FM, Myones BL, et al. Lymphocyte abnormalities and complement activation in Kawasaki disease. Proc Clin Biol Res. 1987;250:175–84. 7. Takei S, Arora YK, Walker SM. Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens. J Clin Invest. 1993;91:602–7. 8. Gelfand EW. Intravenous immune globulin in autoimmune and inflammatory disease. N Engl J Med. 2012;367:2015–25. 9. Misbah SA, Chapel HM. Adverse effects of intravenous immunoglobulin. Drug Safety. 1993;9:254–62.
CASE REPORT
Intravenous human immunoglobulin for treatment of folliculitis decalvans Nuriah Ismail, Nicola Ralph, and Gillian Murphy
J Dermatolog Treat Downloaded from informahealthcare.com by Nyu Medical Center on 05/20/15 For personal use only.
Department of Dermatology, Beaumont Hospital, Dublin, Ireland
Abstract
Keywords
We report a case of folliculitis decalvans (FD) successfully treated with intravenous human immunoglobulin (HIG). Many conventional treatments with topical agents and oral antibiotics had failed to achieve disease remission, treatment with HIG at a dose of 2 g/kg for the first month, reduced to 1 g/kg for second to fourth months was therefore started, which resulted in rapid improvement and ultimately complete resolution of FD. Clinical improvement was noted after the first infusion of HIG and remission of inflammation was achieved after the fourth infusion. Disease remission was sustained for six months following the last HIG infusion. The exact mechanism of action of HIG is poorly understood. However, it is thought to act as an immunomodulatory agent by altering different components of immune functions. To our knowledge, this is the first case reported in the literature of FD successfully treated with intravenous HIG.
Cicatricial alopecia, folliculitis decalvans, human immunoglobulin, IVIG, scarring alopecia
Introduction Folliculitis decalvans (FD) is a rare inflammatory disorder predominantly occurring in young and middle-aged adults with a slight preponderance of the male gender. It usually affects the vertex and occipital area of the scalp, with areas of erythema, follicular hyperkeratosis, erosions, crusts and scarring alopecia causing pain, itching and burning sensations on the scalp (1). FD is a highly distressing condition that is usually resistant to many treatments.
Report A 29-year old Caucasian male presented with a six year history of recurrent cicatricial alopecia with purulent and tufted folliculitis at the vertex of the scalp (Figure 1). He had multiple disappointing treatments over the years including topical and oral steroids and long-term oral antibiotics. Dermatological examination revealed no concomitant skin diseases and review of systems was unremarkable for any immunodeficiency diseases. Laboratory investigations of full blood count, renal and liver profile, anti-nuclear antibody, anti-extractable nuclear antigens, complement level, serum protein electrophoresis and immunoglobulins were all within normal range except for marginally low lymphocyte count at 1.3 109/L (normal range 1.5–4.0 109/L). Diagnostic skin punch biopsy was carried out and histology showed follicular and perifollicular rupture with a marked predominantly neutrophilic acute and chronic inflammatory infiltrate in the superficial and mid-dermis. Periodic acid-Schiff (PAS) stain preparation showed no fungal element. A diagnosis
History Received 7 January 2015 Revised 27 January 2015 Accepted 27 January 2015 Published online 23 March 2015
of FD was made. The patient had previously taken a combination of rifampicin and clindamycin, both at a dosage of 300 mg twice daily for three months with no clinical improvement. Repeated swabs on the area showed persistent Staphylococcus aureus growth that was sensitive to all the antibiotics tested. The patient was commenced on oral flucloxacillin at a dose of 500 mg four times a day, despite which he continued to have refractory deep and inflammatory papules, erythema and suppurative patches of alopecia. On the basis of case series of intramuscular use of immunoglobulin (2), the decision was made to commence him on immunoglobulin. We chose the intravenous rather than the intramuscular route as a method of administration of human immunoglobulin (HIG). The reason for this was the intramuscular route can be painful for the patient as reported from the case series (2). The patient was started on monthly infusions of FlebogammaÕ , a HIG which is an off-label treatment for FD at a dose of 2 g per kilogram (g/kg) for the first month, reduced to 1 g/kg for second to fourth months. Concomitant treatment with oral flucloxacillin was discontinued after the third infusion of HIG. Overall, the patient had four infusions with a total dose of 425 g of HIG over this four-month period (patient’s bodyweight 85 kg). The patient started to show clinical improvement after the first infusion of HIG, with less erythema, scaling and suppuration of the affected scalp. He complained of a transient headache after the first high-dose infusion. He had no other side effects of the treatment. Disease remission was noted after the fourth infusion of HIG (Figure 2). The patient continued to use only cicloprox olamine shampoo after the infusion. Complete resolution of FD was sustained for six months after the last infusion of HIG.
Discussion Correspondence: Nuriah Ismail, Department of Dermatology, Beaumont Hospital, Dublin 9, Ireland. Tel: +353 0 18092752. Fax: +353 0 18093370. E-mail: [email protected]
FD is an uncommon neutrophilic inflammation of the scalp characterised by painful, recurrent follicular exudation progressing to primary cicatricial alopecia (1). It was first described by
2
N. Ismail et al.
J Dermatolog Treat Downloaded from informahealthcare.com by Nyu Medical Center on 05/20/15 For personal use only.
Figure 1. Pre-treatment with human immunoglobulin.
J Dermatolog Treat, Early Online: 1–2
It consists primarily of the antibody immunoglobulin G (IgG) with small amounts of IgM, IgA and other serum proteins. HIG can be given via intravenous, subcutaneous or intramuscular route. Literature review of the role of intravenous immunoglobulin in the treatment of FD revealed no previous reports of its use. Goo et al. reported good response of 63 patients treated with intramuscular HIG for recalcitrant suppurative diseases, three of them had a diagnosis of FD (2). HIG has been used in various dermatological diseases, some with very little understanding of its exact pharmacodynamics on the diseases. HIG is thought to act as an immunomodulatory and anti-inflammatory agent by altering different components of immune functions, with innate and adaptive pathways in immune systems being potentially targeted. It was well described in patients with Kawasaki disease for which treatment with HIG led to reduction in inflammatory markers (6). Studies for which many were in vitro or animal models showed decrease in the production of proinflammatory cytokines, the down-regulation of adhesion molecules and the neutralisation of superantigens (7). Generally, the dosage of HIG used to treat autoimmune and inflammatory diseases is four to five times higher than those used in patients with immunodeficiency states (8). HIG is generally well tolerated; with common adverse effects including headache and alteration of blood pressure during infusion. More rare and severe complications including renal failure, thrombosis, pulmonary embolism and stroke have also been reported. In IgA-deficient patients, anaphylaxis has been reported (9). In conclusion, we report a case of FD successfully treated with intravenous HIG. Given the fact that the patient only responded after the HIG was commenced and the improvement was sustained after oral flucloxacillin was discontinued, showed that HIG contributed to the therapeutic effect. We propose larger prospective studies are needed to evaluate the use of HIG in the treatment of FD.
Declaration of interest The authors report no declaration of interest. Figure 2. Post-treatment with human immunoglobulin.
References Quinquaud on case of ‘‘folliculite e´pilante et destructive des regions velues’’ in 1888 (3). Brocq et al. in 1905 later coined the term ‘‘folliculitis decalvans’’ and distinguished it from other types of cicatricial alopecia. The aetiology of FD remains unclear. It was thought to be due to abnormal host response to S. aureus although this remains controversial (4). One hypothesis outlined the role of S. aureus in hair follicles infection causing local inflammation with recruitment of neutrophils and several other pro-inflammatory and profibrotic mediators in perifollicular dermis leading to fibrosis (5). Antimicrobial agents remain the first-line therapy for FD with or without microbiological evidence on the swab culture from these lesions. The disease tends to be chronic and recurrent in the majority of patients and anti-staphylococcal treatments are not always effective. Other treatments used for FD are topical, intralesional and oral steroids, topical antiseptic substances, isotretinoin and dapsone with variable response (1). HIG is a blood product with concentrated antibody-containing solution prepared from plasma obtained from human donors.
1. Otberg N, Kang H, Alzolibani AA, et al. Folliculitis decalvans. Dermatol Ther. 2008;21:238–44. 2. Goo B, Chung HJ, Chung WG, et al. Intramuscular immunoglobulin for recalcitrant suppurative diseases of the skin: a retrospective review of 63 cases. Br J Dermatol. 2007;157:563–8. 3. Quinquaud E. Folliculite e´pilante et destructive des regions values. Bull Mem Soc Hop Paris. 1888;5:395–8. 4. Powell JJ, Dawber RPR, Gatter K. Folliculitis decalvans including tufted folliculitis: clinical, histological and therapeutic findings. Br J Dermatol. 1999;140:328–33. 5. Chiarini C, Torchia D, Bianchi B, et al. Immunopathogenesis of folliculitis decalvans. Clues in early lesions. Am J Clin Pathol. 2008; 130:526–34. 6. Laxer RM, Schaffer FM, Myones BL, et al. Lymphocyte abnormalities and complement activation in Kawasaki disease. Proc Clin Biol Res. 1987;250:175–84. 7. Takei S, Arora YK, Walker SM. Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens. J Clin Invest. 1993;91:602–7. 8. Gelfand EW. Intravenous immune globulin in autoimmune and inflammatory disease. N Engl J Med. 2012;367:2015–25. 9. Misbah SA, Chapel HM. Adverse effects of intravenous immunoglobulin. Drug Safety. 1993;9:254–62.
