Letters to the Editor
174
6 Ouazzani A, de Fontaine S, Berthe JV. Extracranial meningioma and pregnancy: a rare diagnosis. J Plast Reconstr Aesthet Surg 2007; 60: 622–625. 7 Shaw R, Kissun D, Boyle M, Triantafyllou A. Primary meningioma of the scalp as a late complication of skull fracture: case report and literature review. Int J Oral Maxillofac Surg 2004; 33: 509–511.
(a)
DOI: 10.1111/jdv.12679
Severe fatigue based on anaemia in patients with hidradenitis suppurativa: report of two cases and a review of the literature Editor Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease.1 Patients often report fatigue, which is generally attributed to the debilitating psychosocial impact of HS.2,3 However, sometimes severe anaemia causes the fatigue. The co-occurrence of HS and anaemia is mentioned in reviews on the disease,1,4 but they refer to a single case series from 1968.5 Since, no studies have been published on this subject. Therefore, we present two representative cases of severe HS with fatigue, based on chronic marked anaemia. The first case is a 46-year-old, otherwise healthy, man with a 6-year history of HS, Hurley stage III, on his buttocks, groin and peri-genital area. He presented with purulent blood loss from his HS lesions and intense fatigue (Fig. 1a). Previous treatments with isotretinoin and multiple antibiotics were ineffective. Laboratory tests revealed a microcytic anaemia (haemoglobin (Hb): 4.5 mmol/L) (Table 1), for which he received three packed cells and was referred to internal medicine. Colonoscopy revealed no abnormalities, gastroscopy was discontinued because of patient’s anxiety. Helicobacter Pylori-breathing test was negative. Iron supplementation was started, temporarily improving his haemoglobin level. Clindamycin 3dd200 mg yielded minor effect on his HS. Extensive wide excision was performed of all HS affected skin with closure by split-skin grafting. Six months postoperatively the wounds were healed (Fig. 1b), his fatigue resolved and his haemoglobin level normalized (Hb: 9.4 mmol/L) (Table 1). The second case is a 61-year-old woman, suffering from HS since the age of 14, Hurley stage III, located in the axillae, groin, pubic and gluteal area. She had a medical history of fatigue, diabetes and hypertension. Previous treatments with antibiotics were ineffective. Laboratory testing revealed normocytic anaemia (Hb: 5.0 mmol/L) (Table 1). She was referred to internal medicine who concluded that her anaemia was caused by iron deficiency and chronic disease, since no other cause was found. She received multiple blood transfusions, temporarily increasing her haemoglobin. Adalimumab was started for her HS, with modest
JEADV 2016, 30, 124–200
(b)
Figure 1 Hidradenitis suppurativa in a 46-year-old male. (a) at first presentation, note the sanguineous discharge from the fistulas. (b) 6 months after extensive surgery.
efficacy. Multiple extensive surgical excisions were performed on her axillae, groin and gluteal area, with subsequent blood loss requiring blood transfusions. Hereafter infliximab infusions were started. The remaining HS lesions improved and the haemoglobin level normalized (Hb 8.5 mmol/L) (Table 1). HS patients often report fatigue, which is attributed to the debilitating course and great psychological impact of HS.2,3 However, a more general underlying cause, chronic marked anaemia, is sometimes overlooked. In 1968, Tennant et al. reported on anaemia associated with HS.5 In their population, 10 of 42 (24%) patients with severe HS had marked anaemia (Hb < 6.3 mmol/L). They concluded that anaemia was probably caused by chronic inflammatory processes.5 Anaemia as consequence of chronic disease is believed to be caused by the effects of elevated levels of pro-inflammatory cytokines.6 Interferon-c, interleukin (IL)- 1 and tumour necrosis factor alpha (TNF-a) can inhibit renal production of erythropoietin and reduce its physiological effect on the bone marrow.6,7 In addition, these
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
↑ 48 mg/L — ↑ 86 mg/L CRP (n: 0.0–9.0 mg/L)
↑, enhanced level; ↓, decreased level; CRP, C-reactive protein; MCV, mean corpuscular volume; n, normal value; RDW, red blood cell distribution width.
226 mg/L
↑
— — ↑ 15.8*109/L ↑ 18.0*109/L Leucocytes (n: 3.5–10.0*109/L)
331*109/L ↑ 590*109/L ↑ 395*109/L ↑ Thrombocytes (n: 150–370*109/L)
937*109/L
14.5% ↑ 18.9% 16.9% ↑ RDW (n: 12–16%)
19.2%
↑
117 fL 84 fL 91 fL ↓ 67 fL MCV (n: 80–100 fL)
— ↓ 3.17*1012/L 4.98*1012/L ↓
JEADV 2016, 30, 124–200
Erythrocytes (n: 4.40–5.60*1012/L)
3.95*1012/L
0.41 l/L ↓ 0.27 l/L 0.45 l/L ↓ Haematocrit (n: 0.40–0.50 l/L)
0.27 l/L
8.5 mmol/L ↓ 5.0 mmol/L 9.4 mmol/L ↓
First presentation First presentation
4.5 mmol/L Haemoglobin (n: male: 8.6–10.5 mmol/L,female: 7.5–8.5 mmol/L)
Table 1 Laboratory values of the first and second case
Case 1: 46-year-old male
6 months after extensive surgery
Case 2: 61-year-old female
After 6 months of infliximab therapy
↑
175
cytokines can enhance the uptake of iron by activated macrophages,6 whereas TNF-a can also decrease the intestinal iron absorption,8,9 both resulting in less iron available for erythropoiesis. In HS, elevated levels of IL-1ß, IL-10 and TNF-a have been demonstrated.10 We argue that these increased cytokine levels contribute to the development of anaemia in patients with severe HS. In addition, HS patients can lose significant amounts of blood via sanguineous drainage from their fistulas, also contributing to the development or preservation of anaemia. In conclusion, fatigue is often mentioned by HS patients and can be caused by severe anaemia. It is important to check for anaemia, especially when considering extensive surgery, and because the fatigue can worsen the already poor quality of life of HS patients. I.E. Deckers,1,2,* H.H. van der Zee,1 E.P. Prens1,2 1
Department of Dermatology, 2Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands *Correspondence: I.E. Deckers. E-mail: [email protected]
References 1 Alikhan A, Lynch PJ, Eisen DB. Hidradenitis suppurativa: a comprehensive review. J Am Acad Dermatol 2009; 60: 539–561. 2 Esmann S, Jemec GB. Psychosocial impact of hidradenitis suppurativa: a qualitative study. Acta Derm Venereol 2011; 91: 328–332. 3 Matusiak L, Bieniek A, Szepietowski JC. Psychophysical aspects of hidradenitis suppurativa. Acta Derm Venereol 2010; 90: 264–268. 4 Jemec GB. Hidradenitis suppurativa. N Engl J Med 2012; 366: 158–164. 5 Tennant F Jr, Bergeron JR, Stone OJ, Mullins JF. Anemia Associated With Hidradenitis Suppurativae. Arch Dermatol 1968; 98: 138. 6 Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005; 352: 1011–1023. 7 Jelkmann W. Proinflammatory cytokines lowering erythropoietin production. J Interf cytokine Res 1998; 18: 555–559. 8 Johnson D, Bayele H, Johnston K et al. Tumour necrosis factor alpha regulates iron transport and transporter expression in human intestinal epithelial cells. FEBS Lett 2004; 573: 195–201. 9 Sharma N, Laftah AH, Brookes MJ et al. A role for tumour necrosis factor alpha in human small bowel iron transport. Biochem J 2005; 390: 437–446. 10 Van der Zee HH, de Ruiter L, van den Broecke DG et al. Elevated levels of tumour necrosis factor (TNF)-a, interleukin (IL)-1b and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-a and IL1b. Br J Dermatol 2011; 164: 1292–1298. DOI: 10.1111/jdv.12680
Epidermolysis bullosa pruriginosa: two novel mutations (A2054V and G2233R) in the COL7A1 gene Editor Epidermolysis bullosa pruriginosa (EBP) (OMIM640129) is an unusual subtype of dystrophic epidermolysis bullosa (DEB),
© 2014 European Academy of Dermatology and Venereology
174
6 Ouazzani A, de Fontaine S, Berthe JV. Extracranial meningioma and pregnancy: a rare diagnosis. J Plast Reconstr Aesthet Surg 2007; 60: 622–625. 7 Shaw R, Kissun D, Boyle M, Triantafyllou A. Primary meningioma of the scalp as a late complication of skull fracture: case report and literature review. Int J Oral Maxillofac Surg 2004; 33: 509–511.
(a)
DOI: 10.1111/jdv.12679
Severe fatigue based on anaemia in patients with hidradenitis suppurativa: report of two cases and a review of the literature Editor Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease.1 Patients often report fatigue, which is generally attributed to the debilitating psychosocial impact of HS.2,3 However, sometimes severe anaemia causes the fatigue. The co-occurrence of HS and anaemia is mentioned in reviews on the disease,1,4 but they refer to a single case series from 1968.5 Since, no studies have been published on this subject. Therefore, we present two representative cases of severe HS with fatigue, based on chronic marked anaemia. The first case is a 46-year-old, otherwise healthy, man with a 6-year history of HS, Hurley stage III, on his buttocks, groin and peri-genital area. He presented with purulent blood loss from his HS lesions and intense fatigue (Fig. 1a). Previous treatments with isotretinoin and multiple antibiotics were ineffective. Laboratory tests revealed a microcytic anaemia (haemoglobin (Hb): 4.5 mmol/L) (Table 1), for which he received three packed cells and was referred to internal medicine. Colonoscopy revealed no abnormalities, gastroscopy was discontinued because of patient’s anxiety. Helicobacter Pylori-breathing test was negative. Iron supplementation was started, temporarily improving his haemoglobin level. Clindamycin 3dd200 mg yielded minor effect on his HS. Extensive wide excision was performed of all HS affected skin with closure by split-skin grafting. Six months postoperatively the wounds were healed (Fig. 1b), his fatigue resolved and his haemoglobin level normalized (Hb: 9.4 mmol/L) (Table 1). The second case is a 61-year-old woman, suffering from HS since the age of 14, Hurley stage III, located in the axillae, groin, pubic and gluteal area. She had a medical history of fatigue, diabetes and hypertension. Previous treatments with antibiotics were ineffective. Laboratory testing revealed normocytic anaemia (Hb: 5.0 mmol/L) (Table 1). She was referred to internal medicine who concluded that her anaemia was caused by iron deficiency and chronic disease, since no other cause was found. She received multiple blood transfusions, temporarily increasing her haemoglobin. Adalimumab was started for her HS, with modest
JEADV 2016, 30, 124–200
(b)
Figure 1 Hidradenitis suppurativa in a 46-year-old male. (a) at first presentation, note the sanguineous discharge from the fistulas. (b) 6 months after extensive surgery.
efficacy. Multiple extensive surgical excisions were performed on her axillae, groin and gluteal area, with subsequent blood loss requiring blood transfusions. Hereafter infliximab infusions were started. The remaining HS lesions improved and the haemoglobin level normalized (Hb 8.5 mmol/L) (Table 1). HS patients often report fatigue, which is attributed to the debilitating course and great psychological impact of HS.2,3 However, a more general underlying cause, chronic marked anaemia, is sometimes overlooked. In 1968, Tennant et al. reported on anaemia associated with HS.5 In their population, 10 of 42 (24%) patients with severe HS had marked anaemia (Hb < 6.3 mmol/L). They concluded that anaemia was probably caused by chronic inflammatory processes.5 Anaemia as consequence of chronic disease is believed to be caused by the effects of elevated levels of pro-inflammatory cytokines.6 Interferon-c, interleukin (IL)- 1 and tumour necrosis factor alpha (TNF-a) can inhibit renal production of erythropoietin and reduce its physiological effect on the bone marrow.6,7 In addition, these
© 2014 European Academy of Dermatology and Venereology
Letters to the Editor
↑ 48 mg/L — ↑ 86 mg/L CRP (n: 0.0–9.0 mg/L)
↑, enhanced level; ↓, decreased level; CRP, C-reactive protein; MCV, mean corpuscular volume; n, normal value; RDW, red blood cell distribution width.
226 mg/L
↑
— — ↑ 15.8*109/L ↑ 18.0*109/L Leucocytes (n: 3.5–10.0*109/L)
331*109/L ↑ 590*109/L ↑ 395*109/L ↑ Thrombocytes (n: 150–370*109/L)
937*109/L
14.5% ↑ 18.9% 16.9% ↑ RDW (n: 12–16%)
19.2%
↑
117 fL 84 fL 91 fL ↓ 67 fL MCV (n: 80–100 fL)
— ↓ 3.17*1012/L 4.98*1012/L ↓
JEADV 2016, 30, 124–200
Erythrocytes (n: 4.40–5.60*1012/L)
3.95*1012/L
0.41 l/L ↓ 0.27 l/L 0.45 l/L ↓ Haematocrit (n: 0.40–0.50 l/L)
0.27 l/L
8.5 mmol/L ↓ 5.0 mmol/L 9.4 mmol/L ↓
First presentation First presentation
4.5 mmol/L Haemoglobin (n: male: 8.6–10.5 mmol/L,female: 7.5–8.5 mmol/L)
Table 1 Laboratory values of the first and second case
Case 1: 46-year-old male
6 months after extensive surgery
Case 2: 61-year-old female
After 6 months of infliximab therapy
↑
175
cytokines can enhance the uptake of iron by activated macrophages,6 whereas TNF-a can also decrease the intestinal iron absorption,8,9 both resulting in less iron available for erythropoiesis. In HS, elevated levels of IL-1ß, IL-10 and TNF-a have been demonstrated.10 We argue that these increased cytokine levels contribute to the development of anaemia in patients with severe HS. In addition, HS patients can lose significant amounts of blood via sanguineous drainage from their fistulas, also contributing to the development or preservation of anaemia. In conclusion, fatigue is often mentioned by HS patients and can be caused by severe anaemia. It is important to check for anaemia, especially when considering extensive surgery, and because the fatigue can worsen the already poor quality of life of HS patients. I.E. Deckers,1,2,* H.H. van der Zee,1 E.P. Prens1,2 1
Department of Dermatology, 2Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands *Correspondence: I.E. Deckers. E-mail: [email protected]
References 1 Alikhan A, Lynch PJ, Eisen DB. Hidradenitis suppurativa: a comprehensive review. J Am Acad Dermatol 2009; 60: 539–561. 2 Esmann S, Jemec GB. Psychosocial impact of hidradenitis suppurativa: a qualitative study. Acta Derm Venereol 2011; 91: 328–332. 3 Matusiak L, Bieniek A, Szepietowski JC. Psychophysical aspects of hidradenitis suppurativa. Acta Derm Venereol 2010; 90: 264–268. 4 Jemec GB. Hidradenitis suppurativa. N Engl J Med 2012; 366: 158–164. 5 Tennant F Jr, Bergeron JR, Stone OJ, Mullins JF. Anemia Associated With Hidradenitis Suppurativae. Arch Dermatol 1968; 98: 138. 6 Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005; 352: 1011–1023. 7 Jelkmann W. Proinflammatory cytokines lowering erythropoietin production. J Interf cytokine Res 1998; 18: 555–559. 8 Johnson D, Bayele H, Johnston K et al. Tumour necrosis factor alpha regulates iron transport and transporter expression in human intestinal epithelial cells. FEBS Lett 2004; 573: 195–201. 9 Sharma N, Laftah AH, Brookes MJ et al. A role for tumour necrosis factor alpha in human small bowel iron transport. Biochem J 2005; 390: 437–446. 10 Van der Zee HH, de Ruiter L, van den Broecke DG et al. Elevated levels of tumour necrosis factor (TNF)-a, interleukin (IL)-1b and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-a and IL1b. Br J Dermatol 2011; 164: 1292–1298. DOI: 10.1111/jdv.12680
Epidermolysis bullosa pruriginosa: two novel mutations (A2054V and G2233R) in the COL7A1 gene Editor Epidermolysis bullosa pruriginosa (EBP) (OMIM640129) is an unusual subtype of dystrophic epidermolysis bullosa (DEB),
© 2014 European Academy of Dermatology and Venereology
