Correspondence
2
3
4
5
results of a multinational case-control study (EuroSCAR). Br J Dermatol 2007; 157: 989–96. Leger F, Machet L, Jan V et al. Acute generalized exanthematous pustulosis associated with paracetamol. Acta Derm Venereol 1998; 78: 222–3. Barbaud A, Collet E, Milpied B et al. A multicenter study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions. Br J Dermatol 2013; 68: 555–62. Jachiet M, Soria A, Gaouar A et al. Toxidermie a l’acetazolamide et tests cutanes: 4 cas. Rev Fr Allergol 2012; 52: 278. Ogoshi M, Yamada Y, Tani M. Acute generalized exanthematic pustulosis induced by cefaclor and acetazolamide. Dermatology 1992; 184: 142–4.
(a)
(b)
Haemophagocytic syndrome with a fatal outcome triggered by parvovirus B19 infection in the skin doi: 10.1111/ced.12208 A 67-year-old white man was hospitalized with fever (40 °C), malaise and chills, which had been present for 2 days. There were no other symptoms or signs, and the patient had been previously well. Laboratory investigations showed that the patient had pancytopenia [haemoglobin 7.9 g/dL (normal range 13.0–18.0 g/dL), leucocytes 13.0–18.0 9 109/L (4–11 9 109/L), and platelets 12 9 109/L (15–300 9 109/L)], elevation of triglycerides (512 mg/dL; normal range 35–160 mg/dL) and ferritin (3948 ng/mL; 15–300 ng/mL), and positivity for IgM against parvovirus B19. However, PCR testing for this virus in the blood was negative. Serum IgM titres for cytomegalovirus, Epstein–Barr virus and herpes simplex virus were negative. The patient was treated with intravenous (IV) Ig 0.5 g/kg (two cycles with a 3-week interval) and broad-spectrum antibiotics, without improvement. Examination of a bone-marrow biopsy found hypoplasia, haemophagocytosis and viral inclusions suggestive of parvovirus infection (Fig. 1a). Immunochemistry for parvovirus gave negative results. On day 30 of admission, the patient developed a skin eruption and was referred to our department. On physical examination, an asymptomatic, purpuric rash was seen on the patient’s trunk and extremities, but sparing the face, palms and soles (Fig. 1–b–c). On histological examination of a skin biopsy, only nonspecific inflammatory changes were seen (Fig. 1d). However, PCR testing for parvovirus B19 DNA was positive in the skin tissue. A diagnosis of haemophagocytic syndrome (HS) was made, and the patient was started on oral prednisolone 1 mg/kg/day; however, this produced little improvement in the haematological parameters. Ten days later, the rash subsided but the patient’s mental status deteriorated, leading to his treatment being changed from oral
222
Clinical and Experimental Dermatology (2014) 39, pp216–234
(c)
(d)
Figure 1 Clinical and histological findings: (a) Bone-marrow
biopsy showing haemophagocytosis (yellow arrows) and viral inclusions (black arrows) (haematoxylin and eosin, original magnification 9100). (b,c) Morbilliform purpuric skin eruption located on (b) the trunk and (c) legs, with a reticular appearance in the latter. (d) Discrete perivascular lymphocytic infiltrate (haematoxylin and eosin, original magnification 9100).
ª 2013 British Association of Dermatologists
Correspondence
prednisolone to IV dexamethasone 10 mg/m2. Further PCR testing for parvovirus B19 DNA in his blood was positive. The patient’s clinical condition worsened, and he died from multiorgan failure. This case illustrates a rare cause of HS with cutaneous involvement. HS can be a primary disease, or can be a reaction to malignancies, autoimmune diseases, or infections, especially by viruses.1 Our patient’s condition fulfilled five of the eight diagnostic criteria for HS, namely bicytopenia, fever, hypertriglyceridaemia, hyperferritinaemia and haemophagocytosis.2 In the few published cases reporting the association of HS with parvovirus B19 infection, there was often an underlying reported disease, most commonly hereditary spherocytosis, and the prognosis was usually favourable compared with other virus-associated HS.1,3 However, it was not possible to exclude the possibility that in our patient the parvovirus infection triggered the HS against the background of an existing haematological disease that could not be discerned because of the bone-marrow hypoplasia. According to Fardet et al.,4 skin involvement occurs in up to 46% of HS cases and may be an early symptom. A generalized, usually transient, nonpruritic maculopapular rash, similar to our patient’s rash, was reported as a common cutaneous finding that may assist in the diagnosis of HS.4 Treatment guidelines recommend the use of etoposide in combination with steroids, especially dexamethasone, in cases with neurological involvement, which penetrates the blood–brain barrier better than prednisolone. IVIg should be considered in patients with ongoing viral infections.2 However, steroids as single agents might be promising.5 In conclusion, we report a fatal case of HS triggered by parvovirus B19 infection in a previously healthy adult. The clinical and molecular results for the associated skin eruption were essential for establishing the correct diagnosis and associated condition. A. F. Pedrosa,1 A. Mota,1,2 P. Morais,1,2 A. Nogueira,1 M. Brochado,3 E. Fonseca,4 and F. Azevedo1 1 Department of Dermatology and Venereology, Centro Hospitalar Sa˜o Joa˜o EPE, Porto, Portugal; 2Department of Dermatology and Venereology, Faculty of Medicine, University of Porto, Porto, Portugal; 3 Department of Clinical Hematology, Centro Hospitalar Sa˜o Joa˜o EPE, Porto, Portugal; and 4Department of Pathology, Centro Hospitalar Sa˜o Joa˜o EPE, Porto, Portugal E-mail: [email protected] Conflict of interest: none declared. Accepted for publication 24 April 2013
References 1 Rouphael NG, Talati NJ, Vaughan C et al. Infections associated with haemophagocytic syndrome. Lancet Infect Dis 2007; 7: 814–22.
ª 2013 British Association of Dermatologists
2 Henter JI, Horne A, Arico M et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007; 48: 124–31. 3 Larroche C, Scieux C, Honderlick P et al. Spontaneous resolution of hemophagocytic syndrome associated with acute parvovirus B19 infection and concomitant Epstein-Barr virus reactivation in an otherwise healthy adult. Eur J Clin Microbiol Infect Dis 2002; 21: 739–42. 4 Fardet L, Galicier L, Vignon-Pennamen MD et al. Frequency, clinical features and prognosis of cutaneous manifestations in adult patients with reactive haemophagocytic syndrome. Br J Dermatol 2010; 162: 547–53. 5 Miura T, Kawakami Y, Sato M et al. Hemophagocytic syndrome occurred in a patient with subcutaneous panniculitis-like T-cell lymphoma without overt skin lesion: successful treatment with steroid pulse therapy. J Dermatol 2011; 38: 1113–15.
Papillary eccrine adenoma should not be mistaken for aggressive digital papillary adenocarcinoma doi: 10.1111/ced.12231 In their article entitled ‘Aggressive digital papillary adenocarcinoma: a review’ in Clinical and Experimental Dermatology, Hsu et al.1 reviewed 18 cases of aggressive digital papillary adenocarcinoma (ADPA) published in the English literature from January 1990 to December 2007 and available on Ovid MEDLINE. In addition, they included one case of their own (case number 19 in the article), who was a 28-year-old woman with a 8 mm nodule that had been present on the dorsal side of her left index finger for more than 10 years. According to the authors, the lesion was excised with a positive margin, and there was no evidence of disease progression at the 6-year follow-up. Although we make no comment about the 18 cases of ADPA collected from the literature, the photomicrographs provided by the authors for their case (Figs 2 and 3 in that article) are clearly not representative of a case of ADPA,2 but rather of papillary eccrine adenoma. The photomicrographs show many tubuloglandular structures in a fibrotic dermis with cystic dilatations and luminal papillary projections. P63 stain (Fig. 3d in the article) demonstrated the presence of an intact outer myoepithelial layer surrounding every tubular and cystic structure. These microscopic features are exactly those of papillary eccrine adenoma, as first proposed by Rulon and Helwig in 1977.3 Whether the so-called ‘papillary eccrine adenoma’ is a true adenoma, that is, a benign glandular neoplasm, is a subject in itself. However, In our view, papillary eccrine adenoma is not adenoma, but carcinoma in situ (unpublished data). Nevertheless, papillary eccrine ade-
Clinical and Experimental Dermatology (2014) 39, pp216–234
223
2
3
4
5
results of a multinational case-control study (EuroSCAR). Br J Dermatol 2007; 157: 989–96. Leger F, Machet L, Jan V et al. Acute generalized exanthematous pustulosis associated with paracetamol. Acta Derm Venereol 1998; 78: 222–3. Barbaud A, Collet E, Milpied B et al. A multicenter study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions. Br J Dermatol 2013; 68: 555–62. Jachiet M, Soria A, Gaouar A et al. Toxidermie a l’acetazolamide et tests cutanes: 4 cas. Rev Fr Allergol 2012; 52: 278. Ogoshi M, Yamada Y, Tani M. Acute generalized exanthematic pustulosis induced by cefaclor and acetazolamide. Dermatology 1992; 184: 142–4.
(a)
(b)
Haemophagocytic syndrome with a fatal outcome triggered by parvovirus B19 infection in the skin doi: 10.1111/ced.12208 A 67-year-old white man was hospitalized with fever (40 °C), malaise and chills, which had been present for 2 days. There were no other symptoms or signs, and the patient had been previously well. Laboratory investigations showed that the patient had pancytopenia [haemoglobin 7.9 g/dL (normal range 13.0–18.0 g/dL), leucocytes 13.0–18.0 9 109/L (4–11 9 109/L), and platelets 12 9 109/L (15–300 9 109/L)], elevation of triglycerides (512 mg/dL; normal range 35–160 mg/dL) and ferritin (3948 ng/mL; 15–300 ng/mL), and positivity for IgM against parvovirus B19. However, PCR testing for this virus in the blood was negative. Serum IgM titres for cytomegalovirus, Epstein–Barr virus and herpes simplex virus were negative. The patient was treated with intravenous (IV) Ig 0.5 g/kg (two cycles with a 3-week interval) and broad-spectrum antibiotics, without improvement. Examination of a bone-marrow biopsy found hypoplasia, haemophagocytosis and viral inclusions suggestive of parvovirus infection (Fig. 1a). Immunochemistry for parvovirus gave negative results. On day 30 of admission, the patient developed a skin eruption and was referred to our department. On physical examination, an asymptomatic, purpuric rash was seen on the patient’s trunk and extremities, but sparing the face, palms and soles (Fig. 1–b–c). On histological examination of a skin biopsy, only nonspecific inflammatory changes were seen (Fig. 1d). However, PCR testing for parvovirus B19 DNA was positive in the skin tissue. A diagnosis of haemophagocytic syndrome (HS) was made, and the patient was started on oral prednisolone 1 mg/kg/day; however, this produced little improvement in the haematological parameters. Ten days later, the rash subsided but the patient’s mental status deteriorated, leading to his treatment being changed from oral
222
Clinical and Experimental Dermatology (2014) 39, pp216–234
(c)
(d)
Figure 1 Clinical and histological findings: (a) Bone-marrow
biopsy showing haemophagocytosis (yellow arrows) and viral inclusions (black arrows) (haematoxylin and eosin, original magnification 9100). (b,c) Morbilliform purpuric skin eruption located on (b) the trunk and (c) legs, with a reticular appearance in the latter. (d) Discrete perivascular lymphocytic infiltrate (haematoxylin and eosin, original magnification 9100).
ª 2013 British Association of Dermatologists
Correspondence
prednisolone to IV dexamethasone 10 mg/m2. Further PCR testing for parvovirus B19 DNA in his blood was positive. The patient’s clinical condition worsened, and he died from multiorgan failure. This case illustrates a rare cause of HS with cutaneous involvement. HS can be a primary disease, or can be a reaction to malignancies, autoimmune diseases, or infections, especially by viruses.1 Our patient’s condition fulfilled five of the eight diagnostic criteria for HS, namely bicytopenia, fever, hypertriglyceridaemia, hyperferritinaemia and haemophagocytosis.2 In the few published cases reporting the association of HS with parvovirus B19 infection, there was often an underlying reported disease, most commonly hereditary spherocytosis, and the prognosis was usually favourable compared with other virus-associated HS.1,3 However, it was not possible to exclude the possibility that in our patient the parvovirus infection triggered the HS against the background of an existing haematological disease that could not be discerned because of the bone-marrow hypoplasia. According to Fardet et al.,4 skin involvement occurs in up to 46% of HS cases and may be an early symptom. A generalized, usually transient, nonpruritic maculopapular rash, similar to our patient’s rash, was reported as a common cutaneous finding that may assist in the diagnosis of HS.4 Treatment guidelines recommend the use of etoposide in combination with steroids, especially dexamethasone, in cases with neurological involvement, which penetrates the blood–brain barrier better than prednisolone. IVIg should be considered in patients with ongoing viral infections.2 However, steroids as single agents might be promising.5 In conclusion, we report a fatal case of HS triggered by parvovirus B19 infection in a previously healthy adult. The clinical and molecular results for the associated skin eruption were essential for establishing the correct diagnosis and associated condition. A. F. Pedrosa,1 A. Mota,1,2 P. Morais,1,2 A. Nogueira,1 M. Brochado,3 E. Fonseca,4 and F. Azevedo1 1 Department of Dermatology and Venereology, Centro Hospitalar Sa˜o Joa˜o EPE, Porto, Portugal; 2Department of Dermatology and Venereology, Faculty of Medicine, University of Porto, Porto, Portugal; 3 Department of Clinical Hematology, Centro Hospitalar Sa˜o Joa˜o EPE, Porto, Portugal; and 4Department of Pathology, Centro Hospitalar Sa˜o Joa˜o EPE, Porto, Portugal E-mail: [email protected] Conflict of interest: none declared. Accepted for publication 24 April 2013
References 1 Rouphael NG, Talati NJ, Vaughan C et al. Infections associated with haemophagocytic syndrome. Lancet Infect Dis 2007; 7: 814–22.
ª 2013 British Association of Dermatologists
2 Henter JI, Horne A, Arico M et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007; 48: 124–31. 3 Larroche C, Scieux C, Honderlick P et al. Spontaneous resolution of hemophagocytic syndrome associated with acute parvovirus B19 infection and concomitant Epstein-Barr virus reactivation in an otherwise healthy adult. Eur J Clin Microbiol Infect Dis 2002; 21: 739–42. 4 Fardet L, Galicier L, Vignon-Pennamen MD et al. Frequency, clinical features and prognosis of cutaneous manifestations in adult patients with reactive haemophagocytic syndrome. Br J Dermatol 2010; 162: 547–53. 5 Miura T, Kawakami Y, Sato M et al. Hemophagocytic syndrome occurred in a patient with subcutaneous panniculitis-like T-cell lymphoma without overt skin lesion: successful treatment with steroid pulse therapy. J Dermatol 2011; 38: 1113–15.
Papillary eccrine adenoma should not be mistaken for aggressive digital papillary adenocarcinoma doi: 10.1111/ced.12231 In their article entitled ‘Aggressive digital papillary adenocarcinoma: a review’ in Clinical and Experimental Dermatology, Hsu et al.1 reviewed 18 cases of aggressive digital papillary adenocarcinoma (ADPA) published in the English literature from January 1990 to December 2007 and available on Ovid MEDLINE. In addition, they included one case of their own (case number 19 in the article), who was a 28-year-old woman with a 8 mm nodule that had been present on the dorsal side of her left index finger for more than 10 years. According to the authors, the lesion was excised with a positive margin, and there was no evidence of disease progression at the 6-year follow-up. Although we make no comment about the 18 cases of ADPA collected from the literature, the photomicrographs provided by the authors for their case (Figs 2 and 3 in that article) are clearly not representative of a case of ADPA,2 but rather of papillary eccrine adenoma. The photomicrographs show many tubuloglandular structures in a fibrotic dermis with cystic dilatations and luminal papillary projections. P63 stain (Fig. 3d in the article) demonstrated the presence of an intact outer myoepithelial layer surrounding every tubular and cystic structure. These microscopic features are exactly those of papillary eccrine adenoma, as first proposed by Rulon and Helwig in 1977.3 Whether the so-called ‘papillary eccrine adenoma’ is a true adenoma, that is, a benign glandular neoplasm, is a subject in itself. However, In our view, papillary eccrine adenoma is not adenoma, but carcinoma in situ (unpublished data). Nevertheless, papillary eccrine ade-
Clinical and Experimental Dermatology (2014) 39, pp216–234
223
