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Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Case report
  5. Discussion
  6. Conclusion
  7. References
  8. CPD questions
  9. Instructions for answering questions

Glomus tumours are benign tumours of the temperature-sensitive neuromyoarterial glomus body, present within the dermis, which are most commonly seen as solitary subungual lesions on the arms. Multiple glomus tumours or glomangiomas are a less common subtype of extradigital glomus tumours, which very rarely present as large plaque-like dermal lesions. Glomangiomas do not often show the classic triad of symptoms associated with glomus tumours, namely: pain, point tenderness on compression, and temperature sensitivity. As a result of this and of their atypical morphology, they can often be misdiagnosed as vascular malformations (VMs), resulting in delayed diagnosis and inappropriate treatment. We report a 29-year-old man with multiple extradigital glomus tumours that had been present since childhood, with the lesion on the patient's leg being the largest plaque-like glomangioma yet reported, to our knowledge. Spectral greyscale and Doppler shift ultrasonography showed multiple, tubulonodular, ectatic, noncompressible, vascular structures with aberrant flow within the thickened dermis. Using magnetic resonance imaging, low to intermediate signal was seen on T1-weighted images and high signal on T2-weighted images, and there was florid enhancement with gadolinium, with no evidence of extension into muscle or bone. Histology showed abnormal, dilated, thin-walled, vascular channels lined with multiple layers of glomus cells, confirming the diagnosis of a glomangioma. We discuss imaging techniques for plaque-like glomangiomas, and review the clinical, radiological and histological characteristics that help differentiate them from other superficial VMs.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Case report
  5. Discussion
  6. Conclusion
  7. References
  8. CPD questions
  9. Instructions for answering questions

Glomus tumours are benign tumours arising from the glomus cells and modified smooth muscles surrounding the Sucquet–Hoyer canal of the thermoregulatory specialized arteriovenous anastomosis within the dermis, called the glomus body.[1-3] The highest concentration of these glomus bodies are seen in the digits, followed by the palms and soles. They account for < 2% of all soft-tissue tumours, and up to 75% are solitary lesions of the hands (65% of which are subungual).[4-6]

Phenotypically, glomus tumours are broadly classified as solitary, multiple (localized or disseminated), and plaque-like.[1, 2] Multiple glomus tumours (MGTs, or glomangiomas) are less common than solitary glomus tumours (SGTs), are more commonly extradigital, and constitute only 10–25% of all glomus tumours.[2, 3] These lesions are not neoplastic, and have the morphology of vascular malformations (VMs), so the term ‘glomulovenous malformation’ (GVM) has been suggested. Compared with solitary tumours, glomangiomas tend to be larger and less well circumscribed, have a male predilection, and present less often with the triad of pain, pinpoint tenderness and hypersensitivity to cold, making it more difficult to differentiate them from other cutaneous VMs.[7, 8]

Plaque-like glomangiomas are extremely rare with, to our knowledge, < 10 previous cases reported previously, and only 4 of these cases showed plaque-like glomangiomas along with multiple disseminated glomus tumours.[2, 9, 10] Although the radiological diagnostic features of SGTs have been extensively reported in the literature, a comprehensive description of the imaging characteristics of plaque-like glomangiomas is lacking.

We present a case of a patient with plaque-like glomangiomas, including a tumour on the lower leg, which we believe is the largest reported to date in this area.[11] We review the imaging, histological and clinical features that can help to differentiate plaque-like glomangiomas from other VMs, which in turn can help to prevent delays in diagnosis and initiation of potentially curative treatment.

Case report

  1. Top of page
  2. Summary
  3. Introduction
  4. Case report
  5. Discussion
  6. Conclusion
  7. References
  8. CPD questions
  9. Instructions for answering questions

A 29-year-old white man presented with a history of nodular, purple, vascular-appearing lesions on the sole and lateral border of his right foot, which had first been noticed at the age of 3 months. These lesions had steadily grown in size with the patient's growth, and had become more symptomatic over the years. Through his adolescent years, further lesions had appeared on his trunk and arms, which had also grown slightly in size. Although these were initially thought to be blue rubber bleb naevi and cavernous haemangiomas, biopsy examination later identified dilated irregular vascular channels surrounded by glomus cells, consistent with a benign glomus tumour or glomangioma. The patient reported that the lesion on his foot had a tendency to bleed when knocked, and that he had experienced at least two severe flare-ups of this lesion every year for the past 3–4 years, which resulted in pain and discomfort, especially on weight-bearing and in hot weather.

On physical examination, a large, indurated, nodular, discoloured and obviously vascular lesion was seen, involving almost two-thirds of the plantar surface including the arch, (Fig. 1a), and lateral border (Fig. 1b) of the foot, and the posteromedial surface of the heel, with maximum dimensions of 100 × 80 mm. The lesion was not particularly tender to touch, but felt warmer than the surrounding skin.

image

Figure 1. Nodular, discoloured, hyperkeratotic and vascular-appearing lesion on (a) the sole of the right foot, extending (b) over the lateral border, (c) plain radiograph showing soft-tissue thickening and irregularity over the lateral border of the foot.

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Plain radiography of the right foot showed irregular soft-tissue thickening of the sole and lateral border, but no obvious bony abnormality Fig. 1(c). Spectral greyscale ultrasonography (US) of the discoloured area showed multiple, prominent, tubulonodular, hypoechoic, noncompressible areas, extending from the dermis through to the fascia (Fig. 2a). The abnormal area was 20 mm at its deepest point, and Doppler imaging showed abnormal arterial and venous flow with the tubulonodular structures (Fig. 2b–d). A subsequent magnetic resonance imaging (MRI) scan with contrast [sagittal short TI inversion recovery (STIR) and T1-weighted images, coronal T1- and T2-weighted images, and postcontrast T1-weighted, fat-saturated images in all three planes] showed multiple round and tubular lesions, > 10 mm in size, within the thickened and hypertrophied dermis, corresponding to the abnormal area on the sole of the foot (Fig. 3a,b). These lesions had a high signal on the T2-weighted and STIR images, a low signal on the T1-weighted images, and were brightly enhanced on the postgadolinium images (Fig. 3c,d). There was no obviously abnormal vascular connection to these lesions, and the underlying soft tissue and bone was normal in appearance, with no evidence of oedema or invasion. Catheter angiography failed to delineate any significant feeder vessels.

image

Figure 2. (a) Greyscale ultrasonography scan of the lesion shows well-demarcated area containing multiple hypoechoic tubulonodular structures in the dermis and subcutaneous tissue; (b–d) Doppler ultrasonography shows (b) flow within these tubulonodular areas with both (c) arterial and (d) venous spectral echo patterns.

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image

Figure 3. (a) Axial and (b) coronal sagittal short TI inversion recovery images showing multiple high-signal round and tubular structures in the dermis, corresponding to the macroscopic lesion. (c) The coronal T1-weighted images showed a low signal within the lesion, and the underlying musculature and bones appeared normal. (d) Axial T1-weighted, fat-saturated, postgadolinium images showed florid enhancement of these tubulonodular structures.

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On review of the histology slides, multiple dilated, irregular vascular channels were seen within the thickened dermis and underlying subcutaneous tissue, surrounded by uniform round cells with eosinophilic cytoplasm and rounded nuclei. These uniform cells occasionally formed solid clumps, and in some areas had a few smooth-muscle cells merging with them (Fig. 4). The final diagnosis was that of a large plaque-like glomangioma or GVM.

image

Figure 4. (a) Well-circumscribed vascular lesion in the deep dermis and subcutis, with (b) vessels enveloped by glomus cells, which have an eosinophilic cytoplasm and central nuclei. Haematoxylin and eosin, original magnification (a) × 20; (b) × 400. (c) The glomus cells stained positive for smooth-muscle actin (original magnification × 200).

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Carbon-dioxide laser therapy for the lesions proved ineffective, and any curative surgery was considered to be potentially too destructive, with unacceptable resultant scarring.

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Case report
  5. Discussion
  6. Conclusion
  7. References
  8. CPD questions
  9. Instructions for answering questions

Glomus tumours are benign tumours arising from the glomus cells and modified smooth muscles that surround the afferent arteriole of the thermoregulatory specialized arteriovenous anastomosis in the dermis, called the glomus body.[1-3] Wood first described glomus tumours in 1812,[12] and in 1924, Masson[13] reported their histological features and origin from the Sucquet Hoyer canal. Bailey[14] coined the term ‘glomangioma’ in 1935 for lesions with dilated vascular channels, seen more often in patients with multiple tumours. In 1936, Touraine was the first to report multiple tumours,[15] while in 1959, Sluiter detailed the points of differentiation between the localized and disseminated forms of glomangiomas.[16]

SGTs constitute 75–90% of all glomus tumours, and are largely found subungually in the fingernails. They are approximately twice as common in women,[7] are usually seen in adulthood, present as well-circumscribed purplish nodules of < 10 mm in size, and are invariably painful and tender.[10] By contrast, MGTs or glomangiomas are much less common, have a male predilection (around 4 : 1),[12] and most often present in childhood and rarely congenitally. There is evidence to suggest that the disseminated type demonstrates autosomal dominant inheritance,[3, 6, 8] and is caused by a mutation in the GLMN gene, resulting in a defective glomulin protein.[6, 17] Approximately 60% of people with GVMs have a family history of similar lesions.[8, 18] Glomangiomas tend to be less painful, and the disseminated form can produce both painful and painless lesions.[19] The classic clinical triad of symptoms seen in SGTs, consisting of pain, point tenderness on palpation, and hypersensitivity to extremes of temperature, is often absent in glomangiomas. The individual lesions themselves can be much larger than SGTs, and are often unencapsulated and less circumscribed.[20] Glomangiomas are characterized by slow blood flow and a tendency to develop over time, often growing along with the patient during childhood and adolescence.[10]

Plaque-like glomangiomas share many of the characteristics of glomangiomas. However, they may not show the typical, raised, cobblestone appearance, and tend instead to present as an area of discoloured, indurated or nodular skin, which is rarely tender to palpation and can occasionally bleed upon minor trauma.[8] They can be much more extensive and larger in size than the other types, and are more symptomatic when large or when they affect weight-bearing areas.[1]

The three histological subtypes of glomus tumours are glomus tumour proper, glomangioma and glomangiomyoma. The glomus tumours proper are by far the commonest, accounting for two-thirds of all diagnosed tumours.[3, 4]

MRI of these lesions typically shows a circumscribed nodular area within the dermis and subcutaneous tissue, which returns an intermediate to low signal on T1-weighted images, high signal on T2-weighted images (sometimes more obvious on the T2-weighted fat-saturated images) and avid postgadolinium enhancement.[21-23] Sometimes a central nidus with a high signal is seen, surrounded by a penumbra of less pronounced high signal.[21] Drape et al.[22] described three different patterns, based on the cellular make-up of glomus tumours: a vascular form, a myxoid form and a solid form. Studies on SGTs have shown MRI to have a high sensitivity (90%) but low specificity (50%), with a positive predictive value of 97% and a negative predictive value of 20%. MRI is therefore useful in establishing whether there is infiltration into the underlying soft tissues or bone, which is a predictor for malignant transformation.[21-23]

SGTs can appear as well-defined hypoechoic lesions on grey-scale US, and occasionally VMs are evident on Doppler images.[24, 25] Sometimes even a small lesion on a limb can result in a fistula-type blood flow on directional Doppler studies in the limb vessels proximal to the lesion, and focal tenderness with probe pressure.[25] The US features of large plaque-like glomangiomas have not yet been described. In our case, US scans of the affected area showed multiple dilated hypoechoic rounded and tubular noncompressible structures within the thickened dermis, which had aberrant flow on Doppler imaging. Digital subtraction angiography can sometimes identify a prominent arterial feeding vessel leading to an area of arterial blush, representing the glomus tumour arteriovenous communication.[25]

Histology, preferably with immunohistochemistry, is recommended to confirm the diagnosis, exclude malignant transformation and identify the appropriate therapy. The characteristic histological findings are of collections of dilated, irregular vascular channels lined by endothelium, surrounded by multiple layers of glomus cells embedded in a fibrous stroma. The glomus cells are monomorphous, round or polygonal in shape, and have large plump, cuboidal nuclei, typical dense bodies and attachment plaques. Immunocytochemical studies have shown that glomus tumours are strongly positive for vimentin and α-smooth-muscle actin, but negative for desmin, supporting the theory that glomus tumours are differentiated from vascular smooth muscle.[1, 10, 15] Nerve fibres and mast cells have also been identified, and these may be responsible for substance P-related pain.[5]

Despite the MRI sensitivity being so high and the symptom pattern being reasonably unique, diagnosis of SGTs on the limbs is often delayed by an average of 7–11 years.[3] Extradigital glomus tumours or glomangiomas are even more difficult to diagnose, as they do not often exhibit the classic symptoms of glomus tumours. This can often result in a significantly delayed diagnosis, and prolonged physical and psychological disability for the patient. These lesions are most commonly mistaken for cavernous VMs, tufted angiomas, arteriovenous malformations and Mafucci syndrome. Unlike VMs, plaque-like glomangiomas cannot be emptied by compression, do not normally involve deep structures, do not contain phleboliths, tend to be hyperkeratotic, and are more likely to be painful on compression, with the pain being worse with larger lesions.[8, 9, 20] Making this differentiation is essential for planning treatment. For example, symptoms from VMs are controlled by external compression, but compression can worsen pain in GVMs, and sclerotherapy is more effective in VMs than in GVMs. Extensive VMs can cause a persistent coagulopathy that may progress to disseminated intravascular coagulopathy after surgical or laser intervention, a phenomenon not yet recorded in large GVMs.[8]

Another major differential diagnosis for multiple glomangiomas is blue rubber bleb naevus syndrome (BRNBS), a condition characterized by multiple cutaneous and gastrointestinal VMs. The naevi here are usually bluish, soft and compressible, and occur on the trunk and arms, as opposed to glomangiomas, which are indurated, relatively noncompressible and hyperkeratotic, and seem to predominantly involve the extremities. It is important to make this differentiation, as patients with BRNBS are prone to clinically significant gastrointestinal bleeding.[7, 9, 26]

Early detection facilitates potentially curative resection of these lesions.[9, 10] Glomus tumours are considered benign tumours, but there have been reports of malignant transformation, mostly in SGTs.[2] Although no cases of malignancy have been reported in the rare plaque-like variant, there is at least one case in the literature in which malignant transformation occurred in a patient with glomangiomas.[27] Apart from nuclear atypia and high mitotic activity, both size (> 20 mm) and depth (deeper lesions being more prone to be malignant) have also been suggested as criteria for determining the risk of malignant transformation.[27, 28]

Surgical resection is the treatment of choice for solitary localized GVMs. However, once these lesions have enlarged beyond segmental boundaries, surgery usually poses unacceptable loss of function and cosmetic impairment. Some studies have shown good results using sclerotherapy with tetradecyl sulfate, polidocanol and hypertonic saline in the treatment of multiple GVMs on the limbs.[29] Ablation with argon, carbon-dioxide or pulsed dye laser can also sometimes help reduce the thickness and symptoms of GVMs.[30]

Conclusion

  1. Top of page
  2. Summary
  3. Introduction
  4. Case report
  5. Discussion
  6. Conclusion
  7. References
  8. CPD questions
  9. Instructions for answering questions

Plaque-like glomangiomas are a rare variant of glomus tumours that have atypical clinical features, which result in difficulties in differentiating them from various cutaneous VMs. Therefore, imaging and histological correlation is essential to confirm the diagnosis, facilitate timely and appropriate treatment, and identify any predictors of malignant transformation. Both surgical intervention and laser therapy are more likely to be curative or at least therapeutic if they are started at an early stage when the lesion is still small. With increasing numbers of imaging studies being dedicated towards finding the causes for foot pain, physicians, pathologists and radiologists need to be aware of this rare condition.

Learning points
  • Large plaque-like glomangiomas are a rare variant of glomus tumours that are often seen in people with congenital MGTs.
  • They are difficult to diagnose clinically, as they do not often present with the classic symptoms associated with SGTs, and are easily mistaken for other, more common VMs.
  • As a result, delay in achieving a definitive diagnosis can prevent early curative treatment in the form of surgical resection.
  • Greyscale and Doppler US together with MRI can help make an early and more definitive diagnosis.
  • Once glomangiomas have grown beyond a certain size, they are difficult to treat, but symptomatic relief can be sought through pulsed dye or carbon-dioxide laser treatment or through sclerotherapy.
  • Although the risk of malignant transformation is very low, adverse factors include size of > 20 mm, deep-seated lesions with evidence of infiltration into muscle and bone, and high mitotic activity on histological sections.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Case report
  5. Discussion
  6. Conclusion
  7. References
  8. CPD questions
  9. Instructions for answering questions
  • 1
    Landthaler M, Braum-Falco O, Eckert F et al. Congenital plaque-like glomus tumors. Arch Dermatol 1990; 126: 12037.
  • 2
    Glick SA, Markstein EA, Herreid P. Congenital Glomangioma: case report and review of world literature. Pediatr Dermatol 1995; 12: 2424.
  • 3
    Schiefer TK, Parker WL, Anakwenze OA et al. Extradigital glomus tumors: a 20-year experience. Mayo Clin Proc 2006; 81: 133744.
  • 4
    Thomann BW, Al Momani Z, Klaue K. Glomus tumours of the foot and ankle: case report of a rare disease and review of literature. Foot Ankle Surg 1998; 4: 1320.
  • 5
    Guizzardi M, Mancini LL, Hendrickx I et al. Multiple glomangioma: a case report and review of the literature. Int J Med Biol Environ 1999; 27: 1235.
  • 6
    Henning JS, Kovich OI, Schaffer JV. Glomulovenous malformations. Dermatol Online J 2007; 13: 1.
  • 7
    Schopp JG, Sra KK, Wilkerson MG. Glomangioma. A case report and review of the literature. Cutis 2009; 83: 247.
  • 8
    Boon LM, Mulliken JB, Enjolras O et al. Glomuvenous malformation (glomangioma) and venous malformations: distinct clinicopathologic and genetic entities. Arch Dermatol 2004; 140: 9716.
  • 9
    Vercellino N, Nozza P, Oddone M, Bava GL. Large plaque-like glomulovenous malformation (glomangioma) simulating venous malformation. Clin Exp Dermatol 2006; 31: 53841.
  • 10
    Requena L, Galvan C, Sanchez Yus E et al. Solitary plaque-like telangiectatic glomangioma. Br J Dermatol 1998; 139: 9025.
    Direct Link:
  • 11
    Lines SP, Hepple S. Glomangioma on the dorsum of a foot: a case report of a large glomangioma. The Foot 2005; 15: 546.
  • 12
    Wood W. On painful subcutaneous tubercles. Edinb Med Surg J 1812; 8: 28391.
  • 13
    Masson P. Subcutaneous glomus tumours: painful subcutaneous nodule. Edinb Med J 1924; 35: 56582.
  • 14
    Bailey OT. The cutaneous glomus and its tumors – glomangiomas. Am J Pathol 1935; 11: 91536.
  • 15
    Touraine A, Renault S, Renault P. [Multiple glomus tumours on the trunk and limbs] (in French). Bull Soc Fr Dermatol Syphiligr 1936; 43: 735.
  • 16
    Sluiter JTF, Postma C. Multiple glomus tumors of the skin. Acta Derm Venerol 1959; 39: 98103.
  • 17
    Brouillard P, Boon LM, Mulliken JB et al. Mutations in a novel factor, glomulin, are responsible for glomuvenous malformations (‘glomangiomas’). Am J Hum Genet 2002; 70: 86674.
  • 18
    Conant MA, Weisenfeld SL. Multiple glomus tumors of the skin. Arch Derm 1971; 103: 4815.
  • 19
    Hueston JT. Multiple painless glomus tumours. Br Med J 1961; 1: 121012.
  • 20
    Myers RS, Lo AK, Pawel BR. The glomangioma in the differential diagnosis of vascular malformations. Ann Plast Surg 2006; 57: 4436.
  • 21
    Al-Qattan MM, Al-Namla A, Al-Thunayan A et al. Magnetic resonance imaging in the diagnosis of glomus tumours of the hand. J Hand Surg Br 2005; 30: 53540.
  • 22
    Drape JL, Idy-Peretti I, Goettmann S. Standard and high resolution magnetic resonance imaging of glomus tumors of toes and fingertips. J Am Acad Dermatol 1996; 35: 5505.
  • 23
    Mohler DG, Lim CK, Martin B. Glomus tumor of the plantar arch: a case report with magnetic resonance imaging findings. Foot Ankle Int 1997; 18: 6724.
  • 24
    Fornage BD. Glomus tumors in the fingers: diagnosis with US. Radiology 1988; 167: 1835.
  • 25
    Kreel L, Thronton A, Pardy BJ. Glomus tumour of the hallux: diagnosis by Doppler-shift ultrasound and digital subtraction angiography. Postgrad Med J 1986; 62: 64751.
  • 26
    Lu R, Krathen RA, Sanchez RL et al. Multiple glomangiomas: potential for confusion with blue rubber naevus syndrome. J Am Acad Dermatol 2005; 52: 7312.
  • 27
    De Chiara A, Apice G, Mori S et al. Malignant glomus tumour: a case report and review of literature. Sarcoma 2003; 7: 8791.
  • 28
    Parsi K, Kossard S. Multiple hereditary glomangiomas: successful treatment with sclerotherapy. Australas J Dermatol 2002; 43: 437.
  • 29
    Folpe AL, Fanburg-Smith JC, Miettinen M et al. Atypical and malignant glomus tumors: analysis of 52 cases with a proposal for the reclassification of glomus tumors. Am J Surg Pathol 2001; 25: 112.
  • 30
    Barnes L, Estes S. Laser treatment of multiple glomus tumors. J Dermatol Surg Oncol 1986; 12: 91215.

CPD questions

  1. Top of page
  2. Summary
  3. Introduction
  4. Case report
  5. Discussion
  6. Conclusion
  7. References
  8. CPD questions
  9. Instructions for answering questions

Learning objective

To gain an overview of the presentation, imaging features, histology and management of large plaque-like glomangiomas.

Question 1

What is the most common presentation of a glomangioma?

  1. a)
    They present with symptoms of pain, pinpoint tenderness and temperature sensitivity.
  2. b)
    They are first noticed in late adulthood.
  3. c)
    They are seen more often in males.
  4. d)
    They are more common than solitary glomus tumours.
  5. e)
    They are much more easily treatable than solitary glomus tumours.

Question 2

What is the most common ultrasonography feature of a glomangioma?

  1. a)
    Abnormal purely arterial flow on Doppler imaging.
  2. b)
    Abnormal purely venous flow on Doppler imaging.
  3. c)
    Abnormal arterial and venous flow on Doppler imaging.
  4. d)
    Calcifications.
  5. e)
    Lesions are much more easily delineated and measurable than on magnetic resonance imaging.

Question 3

What is the most common magnetic resonance imaging feature of a glomangioma?

  1. a)
    A tubulonodular lesion within the muscles, high signal on T1-weighted images and low signal on T2-weighted images.
  2. b)
    A tubulonodular lesion within the muscles, low signal on T1-weighted images and high signal on T2-weighted images.
  3. c)
    A tubulonodular lesion within the dermis, intermediate to low signal on T1-weighted images and high signal on T2-weighted images.
  4. d)
    A tubulonodular lesion within the dermis, high signal on T1-weighted images and high signal on T2-weighted images.
  5. e)
    A tubulonodular lesion within the dermis, high signal on T1-weighted images and low signal on T2-weighted images.

Question 4

What feature on imaging would raise the suspicion of malignant transformation in a glomangioma?

  • a) Invasion of fascia and deep muscle layers.
  • b) Lack of colour flow on Doppler ultrasonography.
  • c) Size < 20 mm.
  • d) Superficially located lesion in the dermis.
  • e) Tenderness with ultrasonography probe pressure.

Question 5

With regard to the treatment of glomangiomas, which is the correct answer?

  1. a)
    No treatment is the best option.
  2. b)
    Larger lesions are more easily surgically resectable.
  3. c)
    Pulsed dye laser/carbon-dioxide laser treatment can help reduce symptoms.
  4. d)
    Sclerotherapy has not been shown to be beneficial in trials.
  5. e)
    Surgery is not an option due to the scarring left behind.

Instructions for answering questions

  1. Top of page
  2. Summary
  3. Introduction
  4. Case report
  5. Discussion
  6. Conclusion
  7. References
  8. CPD questions
  9. Instructions for answering questions

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