Correspondence
vascular or neural routes represent the most plausible underlying mechanisms for the occurrence of this phenomenon. In our patient, zosteriform cutaneous involvement was the first clinical sign of an undiagnosed primary breast carcinoma. The unusual zosteriform distribution of cutaneous metastases, in conjunction with the relatively low incidence of breast malignancies in males,5 may result in delayed diagnosis, inadequate management, and prolonged morbidity in this group of patients. Increased awareness among physicians of the significance of such findings and the early recognition of cutaneous metastases are mandatory for the provision of an optimal treatment strategy. Zoe Apalla, MD, PhD Valeria Chassioti, MD, PhD Demetrios Ioannides, MD, PhD State Clinic Hospital of Skin and Venereal Diseases Thessaloniki Greece E-mail: [email protected] Elena Sotiriou, MD, PhD Despina Papadopoulou, MD, PhD Department of Dermatology (A) Aristotle University of Thessaloniki
Coexistence of psoriasis vulgaris and vitiligo with bullous pemphigoid: a case report
The coexistence of psoriasis and bullous pemphigoid (BP) was described in the literature as early as 1929. Since then less than 100 cases were described worldwide. Almost exclusively, psoriasis precedes the eruption of BP. Interestingly, BP seems to occur in patients with psoriasis at a younger age than sporadic BP. Most previously reported cases attributed the occurrence of BP in psoriasis to topical treatment with anthralin or tar but also phototherapy, such as psoralen + ultraviolet A (PUVA) or narrowband UVB, or to the use of anti-tumor necrosis factor antibodies.1–4 Here we report a case of BP eruption in a psoriatic patient apparently not related to antipsoriatic systemic or topical treatment. Additionally, in this patient, BP and psoriasis coexisted with vitiligo. A 47-year-old Polish woman with a 28-year history of psoriasis vulgaris presented with an extensive eruption that had started three weeks previously with disseminated erythematosquamous plaques, tense bullae, and erosions partially superimposed on pre-existing psoriatic plaques in the sacral area (Fig. 1) and on unaffected skin. In addition, this patient had typical psoriatic plaques on the ª 2014 The International Society of Dermatology
Thessaloniki Greece Aimilios Lallas, MD, PhD Skin Cancer Unit Arcispedale Santa Maria Nuova IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Reggio Emilia Italy
References 1 Savoia P, Fava P, Deboli T, et al. Zosteriform cutaneous metastases: a literature meta-analysis and a clinical report of three melanoma cases. Dermatol Surg 2009; 35: 1355–1363. 2 Rao R, Balachandran C, Rao L. Zosteriform cutaneous metastases: a case report and brief review of literature. Indian J Dermatol Venereol Leprol 2010; 76: 447. 3 Bassioukas K, Nakuci M, Dimou S, et al. Zosteriform cutaneous metastases from breast adenocarcinoma. J Eur Acad Dermatol Venereol 2005; 19: 593–596. 4 Virmani NC, Sharma YK, Panicker NK, et al. Zosteriform skin metastases: clue to an undiagnosed breast cancer. Indian J Dermatol 2011; 56: 726–727. 5 Ly D, Forman D, Ferlay J, et al. An international comparison of male and female breast cancer incidence rates. Int J Cancer 2013; 132: 1918–1926.
knees and scalp as well as vitiliginous macules for 40 years duration on the dorsal aspects of hands and ankles confirmed by histopathological examination. She had a family history of psoriasis with her daughter and siblings of her mother being affected. She had never received PUVA or narrowband UVB therapy. She reported experiencing severe psychic stress a few days before the onset of this bullous eruption. During the current hospitalization, skin biopsies were taken for histopathological and immunofluorescent examinations. Histopathology showed subepidermal blistering with an infiltrate mainly of neutrophils and lymphocytes and a small number of eosinophils. Direct immunofluorescence (DIF) from the perilesional skin revealed neither immunoglobulin nor C3 deposits along the basement membrane zone. However, when DIF (split) was repeated with antibodies against IgG isotypes, the results were negative for IgG1, IgG2, IgG3, and IgM but clearly positive for IgG4 (Fig. 2a). Indirect immunofluorescence assay conducted on monkey esophagus as a substrate demonstrated circulating IgG autoantibodies (titer 1 : 640) against the dermal– epidermal junction (Fig. 2b). ELISA assay confirmed high International Journal of Dermatology 2014, 53, e347–e366
e359
e360
Correspondence
Figure 1 Tense bullae and erosions superimposed on preexisting psoriatic plaques in the sacral area
(a)
(b)
titers of anti-BP180 (>200 VIEU/ml) and anti-BP230 (147 VIEU/ml), VIEU-Vienna units with negative results for anti-envoplakin, anti-Dsg1, anti-Dsg3, and anti-Col7A antibodies. BP was diagnosed, and treatment with oral tetracycline 2 g/day, oral methylprednisolone 8 mg/day, and topical dexamethasone with neomycin in aerosol was started. The bullous eruption was well-controlled within a week without exacerbation of psoriasis. Although large population studies show a significantly increased risk of vitiligo and BP in patients with psoriasis, to the best of our knowledge the presented case of coexistence of psoriasis, vitiligo, and BP is only the second such case described in the literature.5–7 The pathogenic significance of this relationship is unknown. It may be suggested that psoriasis as a chronic inflammatory disease provides a particular predisposition of the immune system that, under certain circumstances, leads to an autoimmune response. However, recent hypotheses suggest a genetic factor for susceptibility to the occurrence of multiple autoimmune disorders.8 One of the most important gene mutations in patients with autoimmune diseases such as vitiligo is the AIRE gene, which is responsible for the development of immunological tolerance and thus prevention of autoimmunity.9 Further work is needed to advance knowledge on the pathophysiological mechanism of this phenomenon. False-negative DIF results, reported previously by other authors, underscore the need for use of isotype-specific antibodies in DIF in case of suspected pemphigoid.10 Marek Jankowski, MD, PhD Rafal Czajkowski, MD, PhD, DSc Kinga Scibior, MSc Department of Dermatology, Sexually Transmitted Diseases and Immunodermatology Ludwik Rydygier Medical College in Bydgoszcz Nicolaus Copernicus University in Torun Bydgoszcz Poland Robert A. Schwartz, MD, MPH Department of Dermatology and Pathology Rutgers University New Jersey Medical School Newark NJ, USA
Figure 2 Positive direct immunofluorescence with anti-IgG4 primary antibody (a). Positive indirect immunofluorescence examination with monkey esophagus as a substrate (magnification 9 40) (b) International Journal of Dermatology 2014, 53, e347–e366
Rafal Czajkowski, MD, PhD, DSC Department of Dermatology, Sexually Transmitted Diseases and Immunodermatology Ludwik Rydygier Medical College in Bydgoszcz Nicolaus Copernicus University in Toru n 9, Skodowskiej-Curie street ª 2014 The International Society of Dermatology
Correspondence
Bydgoszcz 85-094, Poland E-mail: [email protected] Conflicts of interest: None. References 1 Lazarczyk M, Wozniak K, Ischi N, et al. Coexistence of psoriasis and pemphigoid – only a coincidence? Int J Mol Med 2006; 18: 619–623. 2 Barnadas MA, Gilaberte M, Pujol R, et al. Bullous pemphigoid in a patient with psoriasis during the course of PUVA therapy: study by ELISA test. Int J Dermatol 2006; 45: 1089–1092. 3 Corey K, Levin NA, Hure M, et al. Eruption of bullae within psoriatic plaques: a rare adverse effect of narrowband ultraviolet B (NB-UVB) phototherapy. Dermatol Online J 2012; 18: 3. 4 Stausbol-Gron B, Deleuran M, Sommer Hansen E, et al. Development of bullous pemphigoid during treatment of psoriasis with adalimumab. Clin Exp Dermatol 2009; 34: e285–e286.
Successful treatment of Schnitzler syndrome with cyclosporine
Editor, Schnitzler syndrome is a rare autoinflammatory disorder defined by urticarial rash and monoclonal gammopathy.1 Further clinical symptoms include episodes of fever, arthralgia or arthritis, lymphadenopathy, and bone and muscle pain.1 We describe a 51-year-old woman with Schnitzler syndrome. A 51-year-old Japanese woman had suffered from a skin rash, myalgia, conjunctivitis, and high fever for six months. Following the initial attack, she had experienced similar episodes approximately every four weeks; each episode lasted one week, and symptoms resolved completely between episodes. Widespread erythematous edematous plaques with severe pruritus were apparent on the subject’s trunk and extremities during the febrile attacks (Fig. 1a). A biopsy taken from an erythematous area on her right arm revealed a moderate perivascular infiltration of lymphocytes, neutrophils, and histiocytes in the dermis (Fig. 1b). No deposit of monoclonal immunoglobulin M (IgM) was seen in the lesional skin. Laboratory tests demonstrated an elevated erythrocyte sedimentation rate (ESR) of 128 mm/h, C-reactive protein at 12.1 mg/dl (normal range: 0–0.6 mg/dl), elevated ferritin at 348.6 ng/ ml (normal range: 6.2–138 ng/ml), elevated IgM at 648 mg/dl (normal range: 35–220 mg/ml), normal IgG at 999 mg/dl (normal range: 920–1800 mg/ml), and normal IgA at 281 mg/dl (normal range: 110–450 mg/ml). Serum protein electrophoresis demonstrated an M-bow, which was shown to be a monoclonal IgM j-type. No abnormal ª 2014 The International Society of Dermatology
5 Chen YJ, Wu CY, Lin MW, et al. Comorbidity profiles among patients with bullous pemphigoid: a nationwide population-based study. Br J Dermatol 2011; 165: 593– 599. 6 Tsai TF, Wang TS, Hung ST, et al. Epidemiology and comorbidities of psoriasis patients in a national database in Taiwan. J Dermatol Sci 2011; 63: 40–46. 7 Pasic A, Ljubojevic S, Lipozencic J, et al. Coexistence of psoriasis vulgaris, bullous pemphigoid and vitiligo: a case report. J Eur Acad Dermatol Venereol 2002; 16: 426–427. 8 Pender MP. CD8+ T-cell deficiency, Epstein-Barr virus infection, vitamin D deficiency, and steps to autoimmunity: a unifying hypothesis. Autoimmune Dis 2012; 2012: 189096. 9 Fierabracci A. Recent insights into the role and molecular mechanisms of the autoimmune regulator (AIRE) gene in autoimmunity. Autoimmun Rev 2011; 10: 137–143. 10 Buschman KE, Seraly M, Thong HY, et al. A predominant IgG4subclass may be responsible for falsenegative direct immunofluorescence in bullous pemphigoid. J Cutan Pathol 2006; 29: 282–286.
findings were revealed in a bone marrow biopsy. Polymerase chain reaction sequencing of the TNFRSF1A gene was performed but did not show any mutations in exons 1–10. The combination of findings led to a diagnosis of Schnitzler syndrome. The patient’s febrile attacks and skin rash were alleviated by the administration of oral prednisolone at 30 mg/d. However, recurrence was observed when prednisolone was decreased to 15 mg/d. Therefore, oral cyclosporine at 3.0 mg/kg/d was started. Strikingly, cyclosporine successfully suppressed the occurrence of the febrile attacks, skin rash, arthralgia, and muscle pain. However, after two years of this therapy, the patient’s blood pressure rose and the oral administration of cyclosporine was discontinued. At this time, oral administration of colchicine at 1 mg/d was started and was effective in resolving all of her symptoms. Initially, tumor necrosis factor receptor-associated periodic syndrome (TRAPS) was suspected. However, the patient had no mutations in exons 1–10 of the TNFRSF1A gene. Schnitzler described cases with nonpruritic urticaria, intermittent fever of unknown origin, arthralgia or bone pain, increased ESR, and IgM paraproteinemia as Schnitzler syndrome.2 It has since been reported that the absence of pruritus is not necessary for the diagnosis of Schnitzler syndrome because the majority of patients report an intensified itching during the course of the disease.3 The histopathological findings in the present patient showed an infiltration of mononuclear cells around the blood vessels in the upper dermis. Generally, neutrophilic urticarial dermatosis is the most common histopathological pattern in Schnitzler syndrome. International Journal of Dermatology 2014, 53, e347–e366
e361
vascular or neural routes represent the most plausible underlying mechanisms for the occurrence of this phenomenon. In our patient, zosteriform cutaneous involvement was the first clinical sign of an undiagnosed primary breast carcinoma. The unusual zosteriform distribution of cutaneous metastases, in conjunction with the relatively low incidence of breast malignancies in males,5 may result in delayed diagnosis, inadequate management, and prolonged morbidity in this group of patients. Increased awareness among physicians of the significance of such findings and the early recognition of cutaneous metastases are mandatory for the provision of an optimal treatment strategy. Zoe Apalla, MD, PhD Valeria Chassioti, MD, PhD Demetrios Ioannides, MD, PhD State Clinic Hospital of Skin and Venereal Diseases Thessaloniki Greece E-mail: [email protected] Elena Sotiriou, MD, PhD Despina Papadopoulou, MD, PhD Department of Dermatology (A) Aristotle University of Thessaloniki
Coexistence of psoriasis vulgaris and vitiligo with bullous pemphigoid: a case report
The coexistence of psoriasis and bullous pemphigoid (BP) was described in the literature as early as 1929. Since then less than 100 cases were described worldwide. Almost exclusively, psoriasis precedes the eruption of BP. Interestingly, BP seems to occur in patients with psoriasis at a younger age than sporadic BP. Most previously reported cases attributed the occurrence of BP in psoriasis to topical treatment with anthralin or tar but also phototherapy, such as psoralen + ultraviolet A (PUVA) or narrowband UVB, or to the use of anti-tumor necrosis factor antibodies.1–4 Here we report a case of BP eruption in a psoriatic patient apparently not related to antipsoriatic systemic or topical treatment. Additionally, in this patient, BP and psoriasis coexisted with vitiligo. A 47-year-old Polish woman with a 28-year history of psoriasis vulgaris presented with an extensive eruption that had started three weeks previously with disseminated erythematosquamous plaques, tense bullae, and erosions partially superimposed on pre-existing psoriatic plaques in the sacral area (Fig. 1) and on unaffected skin. In addition, this patient had typical psoriatic plaques on the ª 2014 The International Society of Dermatology
Thessaloniki Greece Aimilios Lallas, MD, PhD Skin Cancer Unit Arcispedale Santa Maria Nuova IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Reggio Emilia Italy
References 1 Savoia P, Fava P, Deboli T, et al. Zosteriform cutaneous metastases: a literature meta-analysis and a clinical report of three melanoma cases. Dermatol Surg 2009; 35: 1355–1363. 2 Rao R, Balachandran C, Rao L. Zosteriform cutaneous metastases: a case report and brief review of literature. Indian J Dermatol Venereol Leprol 2010; 76: 447. 3 Bassioukas K, Nakuci M, Dimou S, et al. Zosteriform cutaneous metastases from breast adenocarcinoma. J Eur Acad Dermatol Venereol 2005; 19: 593–596. 4 Virmani NC, Sharma YK, Panicker NK, et al. Zosteriform skin metastases: clue to an undiagnosed breast cancer. Indian J Dermatol 2011; 56: 726–727. 5 Ly D, Forman D, Ferlay J, et al. An international comparison of male and female breast cancer incidence rates. Int J Cancer 2013; 132: 1918–1926.
knees and scalp as well as vitiliginous macules for 40 years duration on the dorsal aspects of hands and ankles confirmed by histopathological examination. She had a family history of psoriasis with her daughter and siblings of her mother being affected. She had never received PUVA or narrowband UVB therapy. She reported experiencing severe psychic stress a few days before the onset of this bullous eruption. During the current hospitalization, skin biopsies were taken for histopathological and immunofluorescent examinations. Histopathology showed subepidermal blistering with an infiltrate mainly of neutrophils and lymphocytes and a small number of eosinophils. Direct immunofluorescence (DIF) from the perilesional skin revealed neither immunoglobulin nor C3 deposits along the basement membrane zone. However, when DIF (split) was repeated with antibodies against IgG isotypes, the results were negative for IgG1, IgG2, IgG3, and IgM but clearly positive for IgG4 (Fig. 2a). Indirect immunofluorescence assay conducted on monkey esophagus as a substrate demonstrated circulating IgG autoantibodies (titer 1 : 640) against the dermal– epidermal junction (Fig. 2b). ELISA assay confirmed high International Journal of Dermatology 2014, 53, e347–e366
e359
e360
Correspondence
Figure 1 Tense bullae and erosions superimposed on preexisting psoriatic plaques in the sacral area
(a)
(b)
titers of anti-BP180 (>200 VIEU/ml) and anti-BP230 (147 VIEU/ml), VIEU-Vienna units with negative results for anti-envoplakin, anti-Dsg1, anti-Dsg3, and anti-Col7A antibodies. BP was diagnosed, and treatment with oral tetracycline 2 g/day, oral methylprednisolone 8 mg/day, and topical dexamethasone with neomycin in aerosol was started. The bullous eruption was well-controlled within a week without exacerbation of psoriasis. Although large population studies show a significantly increased risk of vitiligo and BP in patients with psoriasis, to the best of our knowledge the presented case of coexistence of psoriasis, vitiligo, and BP is only the second such case described in the literature.5–7 The pathogenic significance of this relationship is unknown. It may be suggested that psoriasis as a chronic inflammatory disease provides a particular predisposition of the immune system that, under certain circumstances, leads to an autoimmune response. However, recent hypotheses suggest a genetic factor for susceptibility to the occurrence of multiple autoimmune disorders.8 One of the most important gene mutations in patients with autoimmune diseases such as vitiligo is the AIRE gene, which is responsible for the development of immunological tolerance and thus prevention of autoimmunity.9 Further work is needed to advance knowledge on the pathophysiological mechanism of this phenomenon. False-negative DIF results, reported previously by other authors, underscore the need for use of isotype-specific antibodies in DIF in case of suspected pemphigoid.10 Marek Jankowski, MD, PhD Rafal Czajkowski, MD, PhD, DSc Kinga Scibior, MSc Department of Dermatology, Sexually Transmitted Diseases and Immunodermatology Ludwik Rydygier Medical College in Bydgoszcz Nicolaus Copernicus University in Torun Bydgoszcz Poland Robert A. Schwartz, MD, MPH Department of Dermatology and Pathology Rutgers University New Jersey Medical School Newark NJ, USA
Figure 2 Positive direct immunofluorescence with anti-IgG4 primary antibody (a). Positive indirect immunofluorescence examination with monkey esophagus as a substrate (magnification 9 40) (b) International Journal of Dermatology 2014, 53, e347–e366
Rafal Czajkowski, MD, PhD, DSC Department of Dermatology, Sexually Transmitted Diseases and Immunodermatology Ludwik Rydygier Medical College in Bydgoszcz Nicolaus Copernicus University in Toru n 9, Skodowskiej-Curie street ª 2014 The International Society of Dermatology
Correspondence
Bydgoszcz 85-094, Poland E-mail: [email protected] Conflicts of interest: None. References 1 Lazarczyk M, Wozniak K, Ischi N, et al. Coexistence of psoriasis and pemphigoid – only a coincidence? Int J Mol Med 2006; 18: 619–623. 2 Barnadas MA, Gilaberte M, Pujol R, et al. Bullous pemphigoid in a patient with psoriasis during the course of PUVA therapy: study by ELISA test. Int J Dermatol 2006; 45: 1089–1092. 3 Corey K, Levin NA, Hure M, et al. Eruption of bullae within psoriatic plaques: a rare adverse effect of narrowband ultraviolet B (NB-UVB) phototherapy. Dermatol Online J 2012; 18: 3. 4 Stausbol-Gron B, Deleuran M, Sommer Hansen E, et al. Development of bullous pemphigoid during treatment of psoriasis with adalimumab. Clin Exp Dermatol 2009; 34: e285–e286.
Successful treatment of Schnitzler syndrome with cyclosporine
Editor, Schnitzler syndrome is a rare autoinflammatory disorder defined by urticarial rash and monoclonal gammopathy.1 Further clinical symptoms include episodes of fever, arthralgia or arthritis, lymphadenopathy, and bone and muscle pain.1 We describe a 51-year-old woman with Schnitzler syndrome. A 51-year-old Japanese woman had suffered from a skin rash, myalgia, conjunctivitis, and high fever for six months. Following the initial attack, she had experienced similar episodes approximately every four weeks; each episode lasted one week, and symptoms resolved completely between episodes. Widespread erythematous edematous plaques with severe pruritus were apparent on the subject’s trunk and extremities during the febrile attacks (Fig. 1a). A biopsy taken from an erythematous area on her right arm revealed a moderate perivascular infiltration of lymphocytes, neutrophils, and histiocytes in the dermis (Fig. 1b). No deposit of monoclonal immunoglobulin M (IgM) was seen in the lesional skin. Laboratory tests demonstrated an elevated erythrocyte sedimentation rate (ESR) of 128 mm/h, C-reactive protein at 12.1 mg/dl (normal range: 0–0.6 mg/dl), elevated ferritin at 348.6 ng/ ml (normal range: 6.2–138 ng/ml), elevated IgM at 648 mg/dl (normal range: 35–220 mg/ml), normal IgG at 999 mg/dl (normal range: 920–1800 mg/ml), and normal IgA at 281 mg/dl (normal range: 110–450 mg/ml). Serum protein electrophoresis demonstrated an M-bow, which was shown to be a monoclonal IgM j-type. No abnormal ª 2014 The International Society of Dermatology
5 Chen YJ, Wu CY, Lin MW, et al. Comorbidity profiles among patients with bullous pemphigoid: a nationwide population-based study. Br J Dermatol 2011; 165: 593– 599. 6 Tsai TF, Wang TS, Hung ST, et al. Epidemiology and comorbidities of psoriasis patients in a national database in Taiwan. J Dermatol Sci 2011; 63: 40–46. 7 Pasic A, Ljubojevic S, Lipozencic J, et al. Coexistence of psoriasis vulgaris, bullous pemphigoid and vitiligo: a case report. J Eur Acad Dermatol Venereol 2002; 16: 426–427. 8 Pender MP. CD8+ T-cell deficiency, Epstein-Barr virus infection, vitamin D deficiency, and steps to autoimmunity: a unifying hypothesis. Autoimmune Dis 2012; 2012: 189096. 9 Fierabracci A. Recent insights into the role and molecular mechanisms of the autoimmune regulator (AIRE) gene in autoimmunity. Autoimmun Rev 2011; 10: 137–143. 10 Buschman KE, Seraly M, Thong HY, et al. A predominant IgG4subclass may be responsible for falsenegative direct immunofluorescence in bullous pemphigoid. J Cutan Pathol 2006; 29: 282–286.
findings were revealed in a bone marrow biopsy. Polymerase chain reaction sequencing of the TNFRSF1A gene was performed but did not show any mutations in exons 1–10. The combination of findings led to a diagnosis of Schnitzler syndrome. The patient’s febrile attacks and skin rash were alleviated by the administration of oral prednisolone at 30 mg/d. However, recurrence was observed when prednisolone was decreased to 15 mg/d. Therefore, oral cyclosporine at 3.0 mg/kg/d was started. Strikingly, cyclosporine successfully suppressed the occurrence of the febrile attacks, skin rash, arthralgia, and muscle pain. However, after two years of this therapy, the patient’s blood pressure rose and the oral administration of cyclosporine was discontinued. At this time, oral administration of colchicine at 1 mg/d was started and was effective in resolving all of her symptoms. Initially, tumor necrosis factor receptor-associated periodic syndrome (TRAPS) was suspected. However, the patient had no mutations in exons 1–10 of the TNFRSF1A gene. Schnitzler described cases with nonpruritic urticaria, intermittent fever of unknown origin, arthralgia or bone pain, increased ESR, and IgM paraproteinemia as Schnitzler syndrome.2 It has since been reported that the absence of pruritus is not necessary for the diagnosis of Schnitzler syndrome because the majority of patients report an intensified itching during the course of the disease.3 The histopathological findings in the present patient showed an infiltration of mononuclear cells around the blood vessels in the upper dermis. Generally, neutrophilic urticarial dermatosis is the most common histopathological pattern in Schnitzler syndrome. International Journal of Dermatology 2014, 53, e347–e366
e361
