Correspondence
2
3
4 5
6
7
8
9
10
over 10 years. Int J Dermatol 2005; 44(Suppl 1): 49–50. Verma SB, Wollina U. Acne keloidalis nuchae: another cutaneous symptom of metabolic syndrome, truncal obesity, and impending/overt diabetes mellitus? Am J Clin Dermatol 2010; 11: 433–436. Ogunbiyi A, George A. Acne keloidalis in females: case report and review of literature. J Natl Med Assoc 2005; 97: 736–738. Dinehart SM, Tanner L, Mallory SB, et al. Acne keloidalis in women. Cutis 1989; 44: 250–252. Akaberi AA, Kafaie P, Noorbala MT, et al. Acne keloidalis nuchae in a Caucasian woman. J Pak Assoc Dermatol 2011; 21: 66–68. Kafaie P, Akaberi A, Hajihoseini H, et al. Acne keloidalis nuchae in a white woman. Iran J Dermatol 2009; 12: 69–70. Knable AL Jr, Hanke CW, Gonin R. Prevalence of acne keloidalis nuchae in football players. J Am Acad Dermatol 1997; 37: 570–574. Wilkerson GB, Bullard JT, Bartal DW. Identification of cardiometabolic risk among collegiate football players. J Athl Train 2010; 45: 67–74. Goh MS, Magee J, Chong AH. Keratosis follicularis spinulosa decalvans and acne keloidalis nuchae. Australas J Dermatol 2005; 46: 257–260. Fonseca CT, Amaral DM, Ribeiro MG, et al. Insulin resistance in adolescents with Down syndrome: a cross-sectional study. BMC Endocr Disord 2005; 5: 6.
Severe atopic dermatitis associated with transient hypogammaglobulinemia of infancy
Atopic dermatitis (AD) is a common chronic inflammatory skin disease, which, in infants, is usually treated with topical steroids and dietary restriction. However, these treatments are often ineffective. In infants, as the expression of maternally derived IgG decreases, serum IgG levels reduce,
(a)
resulting in physiological hypogammaglobulinemia. These levels reach a nadir at the age of 3–4 months and subsequently increase when infant IgG production commences. Transient hypogammaglobulinemia in infancy (THI) is an extension of this physiological hypogammaglobulinemia.1 We report two cases of severe AD associated with THI, both of which improved after the serum IgG levels increased. Case 1 was a 6-month-old boy that developed erythema on both cheeks at two months of age (Fig. 1a), which subsequently spread throughout the body. He was treated with herbal medicine only at another clinic; however, the erythema progressed to scaling and eczema. Therefore, the boy was admitted to our hospital and was treated with topical and intravenous corticosteroids. Case 2 was a 4-month-old girl that developed erythroderma with severe eczema on the face and body and was treated with emollient only for two months at a pediatric clinic. However, the eczema progressed, and she developed phlegmon in the middle finger of the left hand. Thus, she was referred to our hospital, where she was administered topical corticosteroids, intravenous antibiotics, and corticosteroids. As IgE antibodies specific to certain food allergens were elevated in both patients (Table 1), the implicated foods were subsequently avoided. Both patients were diagnosed with AD according to the Japanese guidelines for the management of AD.2 Both patients shared common clinical features, had a similar clinical course, and hypogammaglobulinemia but had no family history of allergy (Table 1). Their eruptions resolved during hospitalization but relapsed after discharge, despite the application of topical corticosteroids. At 10 months of age, their erythema and eczema began to resolve as their serum IgG levels increased. At 16 months of age, the eczema had completely resolved
(b)
Figure 1 Clinical features of the patient (case 1). (a) Clinical features at the age of 6 months. Erythema with scaling and eczema was noted. (b) Clinical features at the age of 16 months. No eczema or erythema was noted ª 2015 The International Society of Dermatology
International Journal of Dermatology 2015, 54, e182–e196
e185
e186
e186 Correspondence
Table 1 Laboratory data of the two patients Case 1 Age (months) 6 27.7 (7.0–15.0) WBC (103cell/ll) CRP (mg/dl) 0.01 (< 0.3) TP (g/dl) 2.9 (5.8–7.3) Alb (g/dl) 1.2 (3.9–4.9) IgG (mg/dl) 50 (440–1033) IgA (mg/dl) 21 (7–29) IgM (IU/ml) 51 (29–126) IgE (IU/ml) 218 (< 20) RAST (score): egg, 5; wheat, 1 Case 2 Age (months) 5 179 (7.0–15.0) WBC (103cell/ll) CRP (mg/dl) 0.01 (< 0.3) TP (g/dl) 5.4 (5.8–7.3) Alb (g/dl) 3.0 (3.9–4.9) IgG (mg/dl) 122 (440–1033) IgA (mg/dl) 7 (7–29) IgM (IU/ml) 76 (28–152) IgE (IU/ml) ND RAST (score): egg, 3; milk, 3; cheese, 3; wheat, 3; soy,
8 90 0 5.4 3.8 203 26 75 ND
8 153 ND 6.8 4.7 227 5 78 188 3
(7.0–15.0) (< 0.3) (5.8–7.3) (3.9–4.9) (440–1033) (7–29) (37–146)
(7.0–15.0) (5.8–7.3) (3.9–4.9) (440–1033) (7–29) (37–186) (< 20)
10 81 0.05 4.9 3.9 329 39 78 87.4
10 137 ND 7.0 4.9 300 10 104 ND
(7.0–15.0) (< 0.3) (5.8–7.3) (3.9–4.9) (440–1033) (7–29) (37–146) (< 20)
(7.0–15.0) (5.8–7.3) (3.9–4.9) (440–1033) (7–29) (37–186)
19 96 0.1 6.2 3.8 667 43 104 190
18 97 0.03 7.3 ND 569 26 159 99
(7.0–11.0) (< 0.3) (6.3–8.0) (3.9–4.9) (665–1343) (12–49) (40–195) (< 30)
(7.0–11.0) (< 0.3) (6.3–8.0) (649–1306) (22–103) (58–309) (< 30)
Alb, albumin; CRP, C-reactive protein; ND, not done; (), reference value; TP, total protein; WBC, white blood cell count; RAST, Radioallergosorbent test.
without corticosteroid treatment (Fig. 1b), and the serum IgG levels reached their normal limits. Currently, both children are healthy and being treated with only a topical emollient. Several studies have reported that hypogammaglobulinemia is associated with severe AD,3 but the precise relationship between these two conditions is unclear. Recent studies have shown that regulatory T-cell (Treg) levels increase in THI patients, and the suppressive effects of Treg cells on B lymphocytes may be associated with the decreased immunoglobulin production.4,5 Interestingly, in both our patients, symptoms resolved with increased serum IgG levels at 16 months of age, and we attribute this to the resolution of THI. A recent study demonstrated that 72% of THI children normalized IgG values within 24 months of age,6 and hence, resolution at 16 months is not improbable. Based on our observations, we hypothesize that in our patients, primary hypogammaglobulinemia with associated THI induced AD. Cutaneous pathogenic microbes can exacerbate atopic eczema in patients with hypogammaglobulinemia, and features of AD are noted in other primary immunodeficiency syndromes, including Wiskott–Aldrich syndrome.7 Thus, patients with THIassociated AD should be administered high-dose topical or oral corticosteroids, antibiotics, and intravenous immunoglobulin (IVIG).8 A recent study showed that IVIG therapy for AD in children improved clinical features and reduced IgE levels,9 suggesting that IVIG therInternational Journal of Dermatology 2015, 54, e182–e196
apy is suitable for THI-associated AD, because IVIG is effective for stopping the vicious circle of infectionimmunodeficiency, as well as for treating AD symptoms.10 In conclusion, THI-associated AD seems to differ from typical AD in terms of the prognosis being more favorable, despite the occurrence of severe eczema with infection due to hypogammaglobulinemia, and serum IgG levels may be a good marker for THI.
Yasuyuki Sumikawa,, MD, PhD Junji Kato,, MD Yuji Kan,, MD, PhD Sayuri Sato,, MD Toshiharu Yamashita,, MD, PhD Department of Dermatology Sapporo Medical University School of Medicine Sapporo Hokkaido Japan E-mail: [email protected] Conflicts of interest: None. References 1 Rosen FS, Cooper MD, Wedgwood RJ. The primary immunodeficiencies. N Engl J Med 1984; 311: 300–310. ª 2015 The International Society of Dermatology
Correspondence
2 Saeki H, Furue M, Furukawa F, et al. Guidelines for management of atopic dermatitis. J Dermatol 2009; 36: 563–577. 3 Yasuno T, Yamasaki A, Maeda Y, et al. Atopic dermatitis and transient hypogammaglobulinemia of infancy improved simultaneously. Pediatr Int 2007; 49: 406–408. 4 Rutkowska M, Lenart M, Bukowska-Strakova K, et al. The number of circulating CD4 + CD25high Foxp3 + T lymphocytes is transiently elevated in the early childhood of transient hypogammaglobulinemia of infancy patients. Clin Immunol 2011; 140: 307–310. 5 Artac H, Kara R, Gokturk B, et al. Reduced CD19 expression and decreased memory B cell numbers in transient hypogammaglobulinemia of infancy. Clin Exp Med 2013; 13: 257–263. 6 Moschese V, Graziani S, Avanzini MA, et al. A prospective study on children with initial diagnosis of transient hypogammaglobulinemia of infancy: results from the Italian Primary Immunodeficiency Network. Int J Immunopathol Pharmacol 2008; 21: 343–352. 7 Saurat JH. Eczema in primary immune-deficiencies. Clues to the pathogenesis of atopic dermatitis with special reference to the Wiskott-Aldrich syndrome. Acta Derm Venereol Suppl (Stockh) 1985; 114: 125–128. 8 Duse M, Iacobini M, Leonardi L, et al. Transient hypogammaglobulinemia of infancy: intravenous immunoglobulin as first line therapy. Int J Immunopathol Pharmacol 2010; 23: 349–353. 9 Turner PJ, Kakakios A, Wong LC, et al. Intravenous immunoglobulin to treat severe atopic dermatitis in children: a case series. Pediatr Dermatol 2012; 29: 177–181. 10 Memmedova L, Azarsiz E, Edeer Karaca N, et al. Does intravenous immunoglobulin therapy prolong immunodeficiency in transient hypogammaglobulinemia of infancy? Pediatr Rep 2013; 5: e14.
Deformity of the earlobe caused by fixed cutaneous sporotrichosis in a pediatric patient
Sporotrichosis is a mycosis caused by the dimorphic fungus Sporothrix schenckii. It generally occurs after traumatic inoculation of soils or foreign organic materials and presents in lymphocutaneous, fixed, or disseminated forms.1 Herein, we report a pediatric patient with fixed cutaneous sporotrichosis on the earlobe caused by an undetermined source. A 9-year-old patient presented with a 3-year history of a recurring ulcerative, crusted lesion with oozing on the left earlobe. Her medical history was not significant except for atopic dermatitis, and she had no history of ear piercing or trauma. Physical examination showed a solitary, crusted, ulcerative lesion measuring 1.0 9 0.5 cm on the lateral edge of her left earlobe (Fig. 1). The patient had undergone ª 2015 The International Society of Dermatology
Figure 1 Clinical examination shows a crusted ulcerative lesion on the lateral edge of the left earlobe in a 9-year-old girl
Figure 2 Histopathology shows suppurative granulomatous inflammation of the dermis from the ulcerative lesion. (Hematoxylin and eosin stain; original magnification 9200)
treatment with broad-spectrum antibiotics and dapsone for a suspected secondary skin infection and mycobacterium infection at another hospital without much improvement. Laboratory and histological workup data from the other hospital could not be provided, but the patient did not recall receiving treatment for fungal infection. A skin biopsy showed the presence of chronic suppurative granulomatous inflammation (Fig. 2). No epidermis was included in the specimen because of the ulceration. Acid-fast bacillus (AFB) and periodic acid-Schiff (PAS) stains failed to demonstrate organisms in the dermis. Tests by polymerase chain reaction (PCR) for the detection of both Mycobacterium tuberculosis and M. tuberculosis complex in the skin sample were negative. Tissue International Journal of Dermatology 2015, 54, e182–e196
e187
2
3
4 5
6
7
8
9
10
over 10 years. Int J Dermatol 2005; 44(Suppl 1): 49–50. Verma SB, Wollina U. Acne keloidalis nuchae: another cutaneous symptom of metabolic syndrome, truncal obesity, and impending/overt diabetes mellitus? Am J Clin Dermatol 2010; 11: 433–436. Ogunbiyi A, George A. Acne keloidalis in females: case report and review of literature. J Natl Med Assoc 2005; 97: 736–738. Dinehart SM, Tanner L, Mallory SB, et al. Acne keloidalis in women. Cutis 1989; 44: 250–252. Akaberi AA, Kafaie P, Noorbala MT, et al. Acne keloidalis nuchae in a Caucasian woman. J Pak Assoc Dermatol 2011; 21: 66–68. Kafaie P, Akaberi A, Hajihoseini H, et al. Acne keloidalis nuchae in a white woman. Iran J Dermatol 2009; 12: 69–70. Knable AL Jr, Hanke CW, Gonin R. Prevalence of acne keloidalis nuchae in football players. J Am Acad Dermatol 1997; 37: 570–574. Wilkerson GB, Bullard JT, Bartal DW. Identification of cardiometabolic risk among collegiate football players. J Athl Train 2010; 45: 67–74. Goh MS, Magee J, Chong AH. Keratosis follicularis spinulosa decalvans and acne keloidalis nuchae. Australas J Dermatol 2005; 46: 257–260. Fonseca CT, Amaral DM, Ribeiro MG, et al. Insulin resistance in adolescents with Down syndrome: a cross-sectional study. BMC Endocr Disord 2005; 5: 6.
Severe atopic dermatitis associated with transient hypogammaglobulinemia of infancy
Atopic dermatitis (AD) is a common chronic inflammatory skin disease, which, in infants, is usually treated with topical steroids and dietary restriction. However, these treatments are often ineffective. In infants, as the expression of maternally derived IgG decreases, serum IgG levels reduce,
(a)
resulting in physiological hypogammaglobulinemia. These levels reach a nadir at the age of 3–4 months and subsequently increase when infant IgG production commences. Transient hypogammaglobulinemia in infancy (THI) is an extension of this physiological hypogammaglobulinemia.1 We report two cases of severe AD associated with THI, both of which improved after the serum IgG levels increased. Case 1 was a 6-month-old boy that developed erythema on both cheeks at two months of age (Fig. 1a), which subsequently spread throughout the body. He was treated with herbal medicine only at another clinic; however, the erythema progressed to scaling and eczema. Therefore, the boy was admitted to our hospital and was treated with topical and intravenous corticosteroids. Case 2 was a 4-month-old girl that developed erythroderma with severe eczema on the face and body and was treated with emollient only for two months at a pediatric clinic. However, the eczema progressed, and she developed phlegmon in the middle finger of the left hand. Thus, she was referred to our hospital, where she was administered topical corticosteroids, intravenous antibiotics, and corticosteroids. As IgE antibodies specific to certain food allergens were elevated in both patients (Table 1), the implicated foods were subsequently avoided. Both patients were diagnosed with AD according to the Japanese guidelines for the management of AD.2 Both patients shared common clinical features, had a similar clinical course, and hypogammaglobulinemia but had no family history of allergy (Table 1). Their eruptions resolved during hospitalization but relapsed after discharge, despite the application of topical corticosteroids. At 10 months of age, their erythema and eczema began to resolve as their serum IgG levels increased. At 16 months of age, the eczema had completely resolved
(b)
Figure 1 Clinical features of the patient (case 1). (a) Clinical features at the age of 6 months. Erythema with scaling and eczema was noted. (b) Clinical features at the age of 16 months. No eczema or erythema was noted ª 2015 The International Society of Dermatology
International Journal of Dermatology 2015, 54, e182–e196
e185
e186
e186 Correspondence
Table 1 Laboratory data of the two patients Case 1 Age (months) 6 27.7 (7.0–15.0) WBC (103cell/ll) CRP (mg/dl) 0.01 (< 0.3) TP (g/dl) 2.9 (5.8–7.3) Alb (g/dl) 1.2 (3.9–4.9) IgG (mg/dl) 50 (440–1033) IgA (mg/dl) 21 (7–29) IgM (IU/ml) 51 (29–126) IgE (IU/ml) 218 (< 20) RAST (score): egg, 5; wheat, 1 Case 2 Age (months) 5 179 (7.0–15.0) WBC (103cell/ll) CRP (mg/dl) 0.01 (< 0.3) TP (g/dl) 5.4 (5.8–7.3) Alb (g/dl) 3.0 (3.9–4.9) IgG (mg/dl) 122 (440–1033) IgA (mg/dl) 7 (7–29) IgM (IU/ml) 76 (28–152) IgE (IU/ml) ND RAST (score): egg, 3; milk, 3; cheese, 3; wheat, 3; soy,
8 90 0 5.4 3.8 203 26 75 ND
8 153 ND 6.8 4.7 227 5 78 188 3
(7.0–15.0) (< 0.3) (5.8–7.3) (3.9–4.9) (440–1033) (7–29) (37–146)
(7.0–15.0) (5.8–7.3) (3.9–4.9) (440–1033) (7–29) (37–186) (< 20)
10 81 0.05 4.9 3.9 329 39 78 87.4
10 137 ND 7.0 4.9 300 10 104 ND
(7.0–15.0) (< 0.3) (5.8–7.3) (3.9–4.9) (440–1033) (7–29) (37–146) (< 20)
(7.0–15.0) (5.8–7.3) (3.9–4.9) (440–1033) (7–29) (37–186)
19 96 0.1 6.2 3.8 667 43 104 190
18 97 0.03 7.3 ND 569 26 159 99
(7.0–11.0) (< 0.3) (6.3–8.0) (3.9–4.9) (665–1343) (12–49) (40–195) (< 30)
(7.0–11.0) (< 0.3) (6.3–8.0) (649–1306) (22–103) (58–309) (< 30)
Alb, albumin; CRP, C-reactive protein; ND, not done; (), reference value; TP, total protein; WBC, white blood cell count; RAST, Radioallergosorbent test.
without corticosteroid treatment (Fig. 1b), and the serum IgG levels reached their normal limits. Currently, both children are healthy and being treated with only a topical emollient. Several studies have reported that hypogammaglobulinemia is associated with severe AD,3 but the precise relationship between these two conditions is unclear. Recent studies have shown that regulatory T-cell (Treg) levels increase in THI patients, and the suppressive effects of Treg cells on B lymphocytes may be associated with the decreased immunoglobulin production.4,5 Interestingly, in both our patients, symptoms resolved with increased serum IgG levels at 16 months of age, and we attribute this to the resolution of THI. A recent study demonstrated that 72% of THI children normalized IgG values within 24 months of age,6 and hence, resolution at 16 months is not improbable. Based on our observations, we hypothesize that in our patients, primary hypogammaglobulinemia with associated THI induced AD. Cutaneous pathogenic microbes can exacerbate atopic eczema in patients with hypogammaglobulinemia, and features of AD are noted in other primary immunodeficiency syndromes, including Wiskott–Aldrich syndrome.7 Thus, patients with THIassociated AD should be administered high-dose topical or oral corticosteroids, antibiotics, and intravenous immunoglobulin (IVIG).8 A recent study showed that IVIG therapy for AD in children improved clinical features and reduced IgE levels,9 suggesting that IVIG therInternational Journal of Dermatology 2015, 54, e182–e196
apy is suitable for THI-associated AD, because IVIG is effective for stopping the vicious circle of infectionimmunodeficiency, as well as for treating AD symptoms.10 In conclusion, THI-associated AD seems to differ from typical AD in terms of the prognosis being more favorable, despite the occurrence of severe eczema with infection due to hypogammaglobulinemia, and serum IgG levels may be a good marker for THI.
Yasuyuki Sumikawa,, MD, PhD Junji Kato,, MD Yuji Kan,, MD, PhD Sayuri Sato,, MD Toshiharu Yamashita,, MD, PhD Department of Dermatology Sapporo Medical University School of Medicine Sapporo Hokkaido Japan E-mail: [email protected] Conflicts of interest: None. References 1 Rosen FS, Cooper MD, Wedgwood RJ. The primary immunodeficiencies. N Engl J Med 1984; 311: 300–310. ª 2015 The International Society of Dermatology
Correspondence
2 Saeki H, Furue M, Furukawa F, et al. Guidelines for management of atopic dermatitis. J Dermatol 2009; 36: 563–577. 3 Yasuno T, Yamasaki A, Maeda Y, et al. Atopic dermatitis and transient hypogammaglobulinemia of infancy improved simultaneously. Pediatr Int 2007; 49: 406–408. 4 Rutkowska M, Lenart M, Bukowska-Strakova K, et al. The number of circulating CD4 + CD25high Foxp3 + T lymphocytes is transiently elevated in the early childhood of transient hypogammaglobulinemia of infancy patients. Clin Immunol 2011; 140: 307–310. 5 Artac H, Kara R, Gokturk B, et al. Reduced CD19 expression and decreased memory B cell numbers in transient hypogammaglobulinemia of infancy. Clin Exp Med 2013; 13: 257–263. 6 Moschese V, Graziani S, Avanzini MA, et al. A prospective study on children with initial diagnosis of transient hypogammaglobulinemia of infancy: results from the Italian Primary Immunodeficiency Network. Int J Immunopathol Pharmacol 2008; 21: 343–352. 7 Saurat JH. Eczema in primary immune-deficiencies. Clues to the pathogenesis of atopic dermatitis with special reference to the Wiskott-Aldrich syndrome. Acta Derm Venereol Suppl (Stockh) 1985; 114: 125–128. 8 Duse M, Iacobini M, Leonardi L, et al. Transient hypogammaglobulinemia of infancy: intravenous immunoglobulin as first line therapy. Int J Immunopathol Pharmacol 2010; 23: 349–353. 9 Turner PJ, Kakakios A, Wong LC, et al. Intravenous immunoglobulin to treat severe atopic dermatitis in children: a case series. Pediatr Dermatol 2012; 29: 177–181. 10 Memmedova L, Azarsiz E, Edeer Karaca N, et al. Does intravenous immunoglobulin therapy prolong immunodeficiency in transient hypogammaglobulinemia of infancy? Pediatr Rep 2013; 5: e14.
Deformity of the earlobe caused by fixed cutaneous sporotrichosis in a pediatric patient
Sporotrichosis is a mycosis caused by the dimorphic fungus Sporothrix schenckii. It generally occurs after traumatic inoculation of soils or foreign organic materials and presents in lymphocutaneous, fixed, or disseminated forms.1 Herein, we report a pediatric patient with fixed cutaneous sporotrichosis on the earlobe caused by an undetermined source. A 9-year-old patient presented with a 3-year history of a recurring ulcerative, crusted lesion with oozing on the left earlobe. Her medical history was not significant except for atopic dermatitis, and she had no history of ear piercing or trauma. Physical examination showed a solitary, crusted, ulcerative lesion measuring 1.0 9 0.5 cm on the lateral edge of her left earlobe (Fig. 1). The patient had undergone ª 2015 The International Society of Dermatology
Figure 1 Clinical examination shows a crusted ulcerative lesion on the lateral edge of the left earlobe in a 9-year-old girl
Figure 2 Histopathology shows suppurative granulomatous inflammation of the dermis from the ulcerative lesion. (Hematoxylin and eosin stain; original magnification 9200)
treatment with broad-spectrum antibiotics and dapsone for a suspected secondary skin infection and mycobacterium infection at another hospital without much improvement. Laboratory and histological workup data from the other hospital could not be provided, but the patient did not recall receiving treatment for fungal infection. A skin biopsy showed the presence of chronic suppurative granulomatous inflammation (Fig. 2). No epidermis was included in the specimen because of the ulceration. Acid-fast bacillus (AFB) and periodic acid-Schiff (PAS) stains failed to demonstrate organisms in the dermis. Tests by polymerase chain reaction (PCR) for the detection of both Mycobacterium tuberculosis and M. tuberculosis complex in the skin sample were negative. Tissue International Journal of Dermatology 2015, 54, e182–e196
e187
