Correspondence
Conflicts of interest: None. References 1 Wozniak K, Kazama T, Kowalewski C. A practical technique for differentiation of subepidermal bullous diseases: localization of in vivo-bound IgG by laser scanning confocal microscopy. Arch Dermatol 2003; 139: 1007–1011. 2 Wolff K, Rappersberger K, Steiner A, et al. Vegetating cicatricial pemphigoid. A new subset of the cicatricial pemphigoid spectrum. Arch Dermatol Res 1987; 279 (Suppl.): S30–S37. 3 Wozniak K, G orkiewicz A, Olszewska M, et al. Cicatricial pemphigoid vegetans. Int J Dermatol 2007; 46: 299–302.
FOXP3 transcription is enhanced in lesional and perilesional skin of patients with focal Alopecia areata
Alopecia areata (AA) is a cell-mediated autoimmune disease, but the mechanism underlying the loss of selftolerance is unknown. We aimed to investigate the breach of self-tolerance in AA by examining the regulatory T cells in situ. Ten patients with focal AA and five age- and sex-matched healthy controls were included in the study. For each patient, three biopsies were obtained from the lesional skin, adjacent normal-appearing skin, and healthy skin. The mRNA expression of FOXP3 was quantified by real-time polymerase chain reaction (PCR) in skin biopsies of patients with focal AA and healthy skin from controls. Analysis of FOXP3 transcription did not suggest any in situ quantitative defect of Tregs. FOXP3 transcription was, by contrast, significantly higher in lesional and perilesional skin of patients with progressive focal AA comparatively to normal skin. Collectively, our data did not support the involvement of in situ deregulation of regulatory T cells in the pathogenesis of focal AA.
Alopecia areata is a common chronic inflammatory disorder of the hair and nails. The clinical features vary from a well-circumscribed patch of hair loss on normalappearing skin (focal AA) to extensive alopecia (AA totalis or universalis).1 The pathogenesis of AA is still uncertain.2 Several data support the evidence of autoimmune mechanisms in AA such as the association of the disease with other classical autoimmune diseases such as vitiligo or thyroid diseases,2 efficacy of immunomodulatory agents, and association with particular HLA alleles.3 Both cellular (CD4+, CD8+) and humoral responses have been implicated.4,5 Recent studies aimed to investigate the breach of peripheral selftolerance in AA by examining the number and function of peripheral regulatory T cells. Such studies showed that peripheral CD4+ CD25+ Treg cell number was not reduced in patients with AA neither in progressive nor in stable forms.6,7 Shin et al.7 demonstrated that patients with focal AA did not exhibit any functional defect of peripheral Tregs. Yet, a defect in the suppressive effect of peripheral Tregs was shown in a patient with an ophiasis pattern, suggesting that Treg cell dysfunction might be implicated in the pathogenesis of this particular clinical form of AA.7 The absence of a quantitative and functional defect of peripheral Tregs in patients with focal AA does not, however, exclude a defect in the recruitment or de novo generation of Tregs in the lesional skin biopsies of patients. Thus, we aimed in this work to investigate the in situ Tregs by assessing the transcription of FOXP3, a master regulator in the development and function of regulatory T cells. Skin biopsies were obtained from 10 patients with focal AA and five age- and sex-matched healthy donors. For each patient, three biopsies were obtained from the lesional skin, adjacent normal-appearing skin, and healthy skin. Clinical features of our patients are shown in Table 1. All experiments were approved by the local eth-
Table 1 Epidemiological and clinical features of Alopecia areata patients No
Age (years)
Gender
Localization
Number of patches
Duration (year)
Evolution
1 2 3 4 5 6 7 8 9 10
16 35 49 38 21 35 28 25 19 21
M F M F M F F F M M
Vertex Scalp Scalp/beard Scalp Scalp/beard Scalp Scalp/beard Scalp Scalp Scalp
1 4 1 1 4 1 4 5–10 3 1
0.33 0.25 0.25 0.06 0.25 0.13 19.00 19.00 0.50 15.00
Progressivea Progressive Progressive Progressive Progressive Stableb Stable Stable Stable Stable
a
Progressive: increase in size and number of lesions during the last 6 months. Stable: the size and number of lesions are the same during the last 6 months.
b
ª 2015 The International Society of Dermatology
International Journal of Dermatology 2015, 54, e315–e326
e319
Correspondence
ics committee, and informed consent was obtained from all patients and donors. The mRNA expression of FOXP3 was quantified in the skin biopsies by real-time reverse transcription–PCR. Total RNA was extracted from frozen biopsies using the RNeasy Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer’s procedures. After reverse transcription, FOXP3 mRNAs were quantified by real-time PCR using available gene expressed assay and Taqman PCR Master Mix in an ABI PRISM 7500 sequence detection system (Applied Biosystems, Branchburg, New Jersey, USA). Data obtained from patients and healthy controls were compared by the non-parametric Mann–Whitney U-test. Statistical significance was assigned to a value of P < 0.05. In situ analysis of FOXP3 mRNA expression did not show any difference between normal skin of patients and that of controls (Fig. 1). FOXP3 transcription was, however, higher in lesional and perilesional skin of patients with focal AA comparatively to normal skin (Fig. 1). The increase in mRNA expression of FOXP3 in lesional and perilesional skin reaches statistical significance (P = 0.01 and P = 0.02, respectively) in patients with progressive forms of focal AA (Fig. 1; data not shown). Natural Tregs play a key role in maintaining peripheral tolerance in vivo through the active suppression of self-reactive T-cell activation and expansion.8 Dysfunction of Tregs has been described in several systemic9 or organ-specific10 autoimmune diseases. Such dysfunction could result from the alteration of their generation or peripheral survival or from an impairment of their sup-
Foxp3 mRNA expression (Arbitrary unit)
e320
0.012
Progressive AA Stable AA
0.01
Ahlem Ben Hmid, MD Nadia Belhadj Hmida, PHD Maha Abdeladhim, PHD Hechmi Louzir, MD Melika Ben Ahmed, MD, PHD Department of Clinical Immunology Institut Pasteur de Tunis Tunis Tunisia E-mail: [email protected]
Healthy controls
0.008 0.006 0.004 0.002 0
pressive functions or their migratory behavior. Investigation of peripheral Tregs in our laboratory (Ben Hmid A, Zaraa I, Ben Ahmed M, unpublished data) are consistent with those of previous studies supporting the absence of a quantitative or functional defect of peripheral Tregs in patients with focal AA. The current analysis of FOXP3 expression in skin biopsies did not suggest any in situ quantitative defect of Tregs in focal AA. The higher FOXP3 transcription in the lesional and perilesional skin of patients with progressive focal AA could be ascribed to a higher recruitment or de novo generation of Tregs or to an enhanced FOXP3 expression within a normal number of Tregs because of lymphocyte activation. Overall, our findings confirm the absence of a quantitative and/or functional defect of Tregs in focal AA and suggest the implication of other lymphocyte subsets in the pathogenesis of the disease. In particular, T-helper 17 lymphocytes should be studied. The latter cells, which are auxiliary lymphocytes producing the proinflammatory cytokine interleukin-17, are incriminated in the pathophysiology of several dysimmune or autoimmune diseases such as multiple sclerosis or rheumatoid polyarthritis.
Lesional skin
Perilesional skin
Healthy skin
Normal skin
Figure 1 Expression of FOXP3 mRNA in the skin of patients with focal AA and controls. Total RNA was extracted from the skin biopsies obtained from ten patients with focal AA (five progressive and five stable) and five healthy controls. After reverse transcription, the expression of the FOXP3 mRNA was analyzed by quantitative real-time reverse transcription–polymerase chain reaction. Data were normalized referring to expression of ribosomal protein, large, PO (RPLPO). Results are expressed in arbitrary units as 2 ΔCT, with ΔCT the difference in threshold cycles for target and reference. AA, alopecia areata. International Journal of Dermatology 2015, 54, e315–e326
Amel Ben Osman, MD Hechmi Louzir, MD Mourad Mokni, MD, PHD Ines Zaraa, MD Melika Ben Ahmed, MD, PHD Faculte de Medecine de Tunis Tunis El Manar University Tunis Tunisia E-mail: [email protected] Amel Ben Osman, MD Mourad Mokni, MD, PHD Ines Zaraa, MD Department of Dermatology La Rabta Hospital Tunis Tunisia ª 2015 The International Society of Dermatology
Correspondence
Funding sources: None. Conflicts of interest: None. References 1 Gilhar A, Etzioni A, Paus R. Alopecia areata. N Engl J Med 2012; 366: 1515–1525. 2 Buffoli B, Rinaldi F, Labanca M, et al. The human hair: from anatomy to physiology. Int J Dermatol 2014; 53: 331–341. 3 Lew BL, Chung JH, Sim WY. Association between IL16 gene polymorphisms and susceptibility to alopecia areata in the Korean population. Int J Dermatol 2014; 53: 319–322. 4 Tobin DJ, Hann SK, Song MS, et al. Hair follicle structures targeted by antibodies in patients with alopecia areata. Arch Dermatol 1997; 133: 57–61. 5 Bodemer C, Peuchmaur M, Fraitaig S, et al. Role of cytotoxic T cells in chronic alopecia areata. J Invest Dermatol 2000; 114: 112–116. 6 Zoller M, McElwee KJ, Vitacolonna M, et al. Apoptosis resistance in peripheral blood lymphocytes of alopecia areata patients. J Autoimmun 2004; 23: 241– 256. 7 Shin BS, Furuhashi T, Nakamura M, et al. Impaired inhibitory function of circulating CD4 + CD25 + regulatory T cells in alopecia areata. J Dermatol Sci 2013; 70: 141–143. 8 Sakaguchi S, Vignali DA, Rudensky AY, et al. The plasticity and stability of regulatory T cells. Nat Rev Immunol 2013; 13: 461–467. 9 Antiga E, Quaglino P, Bellandi S, et al. Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea. Br J Dermatol 2010; 162: 1056– 1063. 10 Ben AM, Zaraa I, Rekik R, et al. Functional defects of peripheral regulatory T lymphocytes in patients with progressive vitiligo. Pigment Cell Melanoma Res 2012; 25: 99–109.
with the following alone or combined systemic therapies: hydroxychloroquine, minocycline, cyclosporine, azathioprine, and methotrexate. These treatments were discontinued due to lack of efficacy or intolerance. She had also been treated with CO2 laser although without success. In view of her marked nasal disfigurement (Fig. 1), significant psychological morbidity, and poor results obtained with previous treatments, we decided to start infliximab therapy. Before starting treatment, complete laboratory studies were performed, including hemogram, biochemistry, urinalysis, serology (HIV, hepatitis B and C), and antinuclear antibodies, all of which were normal or negative. A chest x-ray revealed no signs of tuberculosis, and the Mantoux test was negative. In addition, a scintigraphy with gallium-67 was performed, which showed increased uptake in the nose, right parotid gland, and paratracheal and hilar lymph nodes. Intravenous infliximab was infused at a dose of 5 mg/kg. Infusions were administered at weeks 0, 2, and 6. Methotrexate (10 mg weekly) was added. A rapid and dramatic improvement of her disfiguring cutaneous lesions was noticed after three doses (Fig. 2). A new whole body scintigraphy with gallium-67 was normal. The patient did not present any adverse effects. This treatment regimen was followed by a simple infusion every eight weeks for maintenance therapy. After seven infusions, the skin manifestations completely resolved, and the dose of infliximab was reduced to 3 mg/ kg. When the patient completed nine infusions, due to the very chronic course of the disease, we decided to suspend infliximab and to continue only with methotrexate. However, after discontinuation of infliximab, the skin lesions soon recurred. Infliximab was then reintroduced, achieving a new complete remission of the cutaneous manifestations. Since then, the patient has not had further recurrence after a long follow-up of eight years. (a)
(b)
Refractory highly disfiguring lupus pernio: a dramatic and prolonged response to infliximab
A 59-year-old woman presented to our dermatology clinic 24 years ago because of a violaceous nodule on her nose and a slightly infiltrated plaque on her right cheek. At that time, a diagnosis of lupus pernio was histopathologically confirmed. A chest x-ray revealed bilateral hilar and paratracheal lymphadenopathy without pulmonary parenchymal involvement. Since then, no other extracutaneous manifestations of sarcoidosis were observed. However, her nasal lesion progressively enlarged, causing diffuse violaceous enlargement of the nose. Treatment with potent corticosteroids topically and by intralesional injections only yielded slight improvement of the cutaneous lesions. In addition, the patient had received treatment ª 2015 The International Society of Dermatology
Figure 1 Before infliximab therapy: disfiguring lupus pernio International Journal of Dermatology 2015, 54, e315–e326
e321
Conflicts of interest: None. References 1 Wozniak K, Kazama T, Kowalewski C. A practical technique for differentiation of subepidermal bullous diseases: localization of in vivo-bound IgG by laser scanning confocal microscopy. Arch Dermatol 2003; 139: 1007–1011. 2 Wolff K, Rappersberger K, Steiner A, et al. Vegetating cicatricial pemphigoid. A new subset of the cicatricial pemphigoid spectrum. Arch Dermatol Res 1987; 279 (Suppl.): S30–S37. 3 Wozniak K, G orkiewicz A, Olszewska M, et al. Cicatricial pemphigoid vegetans. Int J Dermatol 2007; 46: 299–302.
FOXP3 transcription is enhanced in lesional and perilesional skin of patients with focal Alopecia areata
Alopecia areata (AA) is a cell-mediated autoimmune disease, but the mechanism underlying the loss of selftolerance is unknown. We aimed to investigate the breach of self-tolerance in AA by examining the regulatory T cells in situ. Ten patients with focal AA and five age- and sex-matched healthy controls were included in the study. For each patient, three biopsies were obtained from the lesional skin, adjacent normal-appearing skin, and healthy skin. The mRNA expression of FOXP3 was quantified by real-time polymerase chain reaction (PCR) in skin biopsies of patients with focal AA and healthy skin from controls. Analysis of FOXP3 transcription did not suggest any in situ quantitative defect of Tregs. FOXP3 transcription was, by contrast, significantly higher in lesional and perilesional skin of patients with progressive focal AA comparatively to normal skin. Collectively, our data did not support the involvement of in situ deregulation of regulatory T cells in the pathogenesis of focal AA.
Alopecia areata is a common chronic inflammatory disorder of the hair and nails. The clinical features vary from a well-circumscribed patch of hair loss on normalappearing skin (focal AA) to extensive alopecia (AA totalis or universalis).1 The pathogenesis of AA is still uncertain.2 Several data support the evidence of autoimmune mechanisms in AA such as the association of the disease with other classical autoimmune diseases such as vitiligo or thyroid diseases,2 efficacy of immunomodulatory agents, and association with particular HLA alleles.3 Both cellular (CD4+, CD8+) and humoral responses have been implicated.4,5 Recent studies aimed to investigate the breach of peripheral selftolerance in AA by examining the number and function of peripheral regulatory T cells. Such studies showed that peripheral CD4+ CD25+ Treg cell number was not reduced in patients with AA neither in progressive nor in stable forms.6,7 Shin et al.7 demonstrated that patients with focal AA did not exhibit any functional defect of peripheral Tregs. Yet, a defect in the suppressive effect of peripheral Tregs was shown in a patient with an ophiasis pattern, suggesting that Treg cell dysfunction might be implicated in the pathogenesis of this particular clinical form of AA.7 The absence of a quantitative and functional defect of peripheral Tregs in patients with focal AA does not, however, exclude a defect in the recruitment or de novo generation of Tregs in the lesional skin biopsies of patients. Thus, we aimed in this work to investigate the in situ Tregs by assessing the transcription of FOXP3, a master regulator in the development and function of regulatory T cells. Skin biopsies were obtained from 10 patients with focal AA and five age- and sex-matched healthy donors. For each patient, three biopsies were obtained from the lesional skin, adjacent normal-appearing skin, and healthy skin. Clinical features of our patients are shown in Table 1. All experiments were approved by the local eth-
Table 1 Epidemiological and clinical features of Alopecia areata patients No
Age (years)
Gender
Localization
Number of patches
Duration (year)
Evolution
1 2 3 4 5 6 7 8 9 10
16 35 49 38 21 35 28 25 19 21
M F M F M F F F M M
Vertex Scalp Scalp/beard Scalp Scalp/beard Scalp Scalp/beard Scalp Scalp Scalp
1 4 1 1 4 1 4 5–10 3 1
0.33 0.25 0.25 0.06 0.25 0.13 19.00 19.00 0.50 15.00
Progressivea Progressive Progressive Progressive Progressive Stableb Stable Stable Stable Stable
a
Progressive: increase in size and number of lesions during the last 6 months. Stable: the size and number of lesions are the same during the last 6 months.
b
ª 2015 The International Society of Dermatology
International Journal of Dermatology 2015, 54, e315–e326
e319
Correspondence
ics committee, and informed consent was obtained from all patients and donors. The mRNA expression of FOXP3 was quantified in the skin biopsies by real-time reverse transcription–PCR. Total RNA was extracted from frozen biopsies using the RNeasy Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer’s procedures. After reverse transcription, FOXP3 mRNAs were quantified by real-time PCR using available gene expressed assay and Taqman PCR Master Mix in an ABI PRISM 7500 sequence detection system (Applied Biosystems, Branchburg, New Jersey, USA). Data obtained from patients and healthy controls were compared by the non-parametric Mann–Whitney U-test. Statistical significance was assigned to a value of P < 0.05. In situ analysis of FOXP3 mRNA expression did not show any difference between normal skin of patients and that of controls (Fig. 1). FOXP3 transcription was, however, higher in lesional and perilesional skin of patients with focal AA comparatively to normal skin (Fig. 1). The increase in mRNA expression of FOXP3 in lesional and perilesional skin reaches statistical significance (P = 0.01 and P = 0.02, respectively) in patients with progressive forms of focal AA (Fig. 1; data not shown). Natural Tregs play a key role in maintaining peripheral tolerance in vivo through the active suppression of self-reactive T-cell activation and expansion.8 Dysfunction of Tregs has been described in several systemic9 or organ-specific10 autoimmune diseases. Such dysfunction could result from the alteration of their generation or peripheral survival or from an impairment of their sup-
Foxp3 mRNA expression (Arbitrary unit)
e320
0.012
Progressive AA Stable AA
0.01
Ahlem Ben Hmid, MD Nadia Belhadj Hmida, PHD Maha Abdeladhim, PHD Hechmi Louzir, MD Melika Ben Ahmed, MD, PHD Department of Clinical Immunology Institut Pasteur de Tunis Tunis Tunisia E-mail: [email protected]
Healthy controls
0.008 0.006 0.004 0.002 0
pressive functions or their migratory behavior. Investigation of peripheral Tregs in our laboratory (Ben Hmid A, Zaraa I, Ben Ahmed M, unpublished data) are consistent with those of previous studies supporting the absence of a quantitative or functional defect of peripheral Tregs in patients with focal AA. The current analysis of FOXP3 expression in skin biopsies did not suggest any in situ quantitative defect of Tregs in focal AA. The higher FOXP3 transcription in the lesional and perilesional skin of patients with progressive focal AA could be ascribed to a higher recruitment or de novo generation of Tregs or to an enhanced FOXP3 expression within a normal number of Tregs because of lymphocyte activation. Overall, our findings confirm the absence of a quantitative and/or functional defect of Tregs in focal AA and suggest the implication of other lymphocyte subsets in the pathogenesis of the disease. In particular, T-helper 17 lymphocytes should be studied. The latter cells, which are auxiliary lymphocytes producing the proinflammatory cytokine interleukin-17, are incriminated in the pathophysiology of several dysimmune or autoimmune diseases such as multiple sclerosis or rheumatoid polyarthritis.
Lesional skin
Perilesional skin
Healthy skin
Normal skin
Figure 1 Expression of FOXP3 mRNA in the skin of patients with focal AA and controls. Total RNA was extracted from the skin biopsies obtained from ten patients with focal AA (five progressive and five stable) and five healthy controls. After reverse transcription, the expression of the FOXP3 mRNA was analyzed by quantitative real-time reverse transcription–polymerase chain reaction. Data were normalized referring to expression of ribosomal protein, large, PO (RPLPO). Results are expressed in arbitrary units as 2 ΔCT, with ΔCT the difference in threshold cycles for target and reference. AA, alopecia areata. International Journal of Dermatology 2015, 54, e315–e326
Amel Ben Osman, MD Hechmi Louzir, MD Mourad Mokni, MD, PHD Ines Zaraa, MD Melika Ben Ahmed, MD, PHD Faculte de Medecine de Tunis Tunis El Manar University Tunis Tunisia E-mail: [email protected] Amel Ben Osman, MD Mourad Mokni, MD, PHD Ines Zaraa, MD Department of Dermatology La Rabta Hospital Tunis Tunisia ª 2015 The International Society of Dermatology
Correspondence
Funding sources: None. Conflicts of interest: None. References 1 Gilhar A, Etzioni A, Paus R. Alopecia areata. N Engl J Med 2012; 366: 1515–1525. 2 Buffoli B, Rinaldi F, Labanca M, et al. The human hair: from anatomy to physiology. Int J Dermatol 2014; 53: 331–341. 3 Lew BL, Chung JH, Sim WY. Association between IL16 gene polymorphisms and susceptibility to alopecia areata in the Korean population. Int J Dermatol 2014; 53: 319–322. 4 Tobin DJ, Hann SK, Song MS, et al. Hair follicle structures targeted by antibodies in patients with alopecia areata. Arch Dermatol 1997; 133: 57–61. 5 Bodemer C, Peuchmaur M, Fraitaig S, et al. Role of cytotoxic T cells in chronic alopecia areata. J Invest Dermatol 2000; 114: 112–116. 6 Zoller M, McElwee KJ, Vitacolonna M, et al. Apoptosis resistance in peripheral blood lymphocytes of alopecia areata patients. J Autoimmun 2004; 23: 241– 256. 7 Shin BS, Furuhashi T, Nakamura M, et al. Impaired inhibitory function of circulating CD4 + CD25 + regulatory T cells in alopecia areata. J Dermatol Sci 2013; 70: 141–143. 8 Sakaguchi S, Vignali DA, Rudensky AY, et al. The plasticity and stability of regulatory T cells. Nat Rev Immunol 2013; 13: 461–467. 9 Antiga E, Quaglino P, Bellandi S, et al. Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea. Br J Dermatol 2010; 162: 1056– 1063. 10 Ben AM, Zaraa I, Rekik R, et al. Functional defects of peripheral regulatory T lymphocytes in patients with progressive vitiligo. Pigment Cell Melanoma Res 2012; 25: 99–109.
with the following alone or combined systemic therapies: hydroxychloroquine, minocycline, cyclosporine, azathioprine, and methotrexate. These treatments were discontinued due to lack of efficacy or intolerance. She had also been treated with CO2 laser although without success. In view of her marked nasal disfigurement (Fig. 1), significant psychological morbidity, and poor results obtained with previous treatments, we decided to start infliximab therapy. Before starting treatment, complete laboratory studies were performed, including hemogram, biochemistry, urinalysis, serology (HIV, hepatitis B and C), and antinuclear antibodies, all of which were normal or negative. A chest x-ray revealed no signs of tuberculosis, and the Mantoux test was negative. In addition, a scintigraphy with gallium-67 was performed, which showed increased uptake in the nose, right parotid gland, and paratracheal and hilar lymph nodes. Intravenous infliximab was infused at a dose of 5 mg/kg. Infusions were administered at weeks 0, 2, and 6. Methotrexate (10 mg weekly) was added. A rapid and dramatic improvement of her disfiguring cutaneous lesions was noticed after three doses (Fig. 2). A new whole body scintigraphy with gallium-67 was normal. The patient did not present any adverse effects. This treatment regimen was followed by a simple infusion every eight weeks for maintenance therapy. After seven infusions, the skin manifestations completely resolved, and the dose of infliximab was reduced to 3 mg/ kg. When the patient completed nine infusions, due to the very chronic course of the disease, we decided to suspend infliximab and to continue only with methotrexate. However, after discontinuation of infliximab, the skin lesions soon recurred. Infliximab was then reintroduced, achieving a new complete remission of the cutaneous manifestations. Since then, the patient has not had further recurrence after a long follow-up of eight years. (a)
(b)
Refractory highly disfiguring lupus pernio: a dramatic and prolonged response to infliximab
A 59-year-old woman presented to our dermatology clinic 24 years ago because of a violaceous nodule on her nose and a slightly infiltrated plaque on her right cheek. At that time, a diagnosis of lupus pernio was histopathologically confirmed. A chest x-ray revealed bilateral hilar and paratracheal lymphadenopathy without pulmonary parenchymal involvement. Since then, no other extracutaneous manifestations of sarcoidosis were observed. However, her nasal lesion progressively enlarged, causing diffuse violaceous enlargement of the nose. Treatment with potent corticosteroids topically and by intralesional injections only yielded slight improvement of the cutaneous lesions. In addition, the patient had received treatment ª 2015 The International Society of Dermatology
Figure 1 Before infliximab therapy: disfiguring lupus pernio International Journal of Dermatology 2015, 54, e315–e326
e321
