A Man with an Umbilicated Papule of A Man with an Umbilicated Papule of the Hand: What Is Your Diagnosis?the Hand: What Is Your Diagnosis?

Deba P. Sarma, Meredith Cox, Paige Walter, Deba P. Sarma, Meredith Cox, Paige Walter, William Crisler, and Christopher Huerter William Crisler, and Christopher Huerter

Creighton University Medical Center, OmahaCreighton University Medical Center, Omaha

AbstractAbstract IntroductionIntroduction. Ecthyma contagiosum is a zoonotic disease . Ecthyma contagiosum is a zoonotic disease

caused by the parapoxvirus that causes “sore mouth” in caused by the parapoxvirus that causes “sore mouth” in sheep and goats and orf in human. sheep and goats and orf in human. Case PresentationCase Presentation. A . A 61-year-old sheep farmer presented with a painful non-61-year-old sheep farmer presented with a painful non-pruritic lesion on the left hand that had been present for pruritic lesion on the left hand that had been present for approximately 5 weeks. Physical examination approximately 5 weeks. Physical examination demonstrated a 1cm pearly, umbilicated papule with demonstrated a 1cm pearly, umbilicated papule with raised borders. A biopsy showed an asymmetrical nodule raised borders. A biopsy showed an asymmetrical nodule with parakeratotic crust and acanthosis with thin with parakeratotic crust and acanthosis with thin epidermal strands extending deeply in the underlying epidermal strands extending deeply in the underlying dermis. Marked edema, capillary proliferation and dermis. Marked edema, capillary proliferation and extensive lymphocytic infiltration was also present. One extensive lymphocytic infiltration was also present. One red intranuclear inclusion was identified in an epidermal red intranuclear inclusion was identified in an epidermal keratinocyte. A diagnosis of human orf (ecthyma keratinocyte. A diagnosis of human orf (ecthyma contagiosum) was made. contagiosum) was made. ConclusionConclusion. Infected sheep and . Infected sheep and freshly vaccinated sheep or goats are the reservoir for freshly vaccinated sheep or goats are the reservoir for human infection. After an incubation period of 3–7 days, human infection. After an incubation period of 3–7 days, parapoxvirus infections produce 1–3 painful lesions parapoxvirus infections produce 1–3 painful lesions measuring 1-2cm in diameter. The natural history of the measuring 1-2cm in diameter. The natural history of the disease is complete resolution and no treatment is disease is complete resolution and no treatment is indicated. Prevention of echthyma contagiosum in indicated. Prevention of echthyma contagiosum in ruminants through vaccination is thought to be the best ruminants through vaccination is thought to be the best way to control infection.way to control infection.

1. Case Synopsis1. Case Synopsis A 61-year-old sheep farmer presented with a painful A 61-year-old sheep farmer presented with a painful

nonpruritic on the left hand that lesion had been present nonpruritic on the left hand that lesion had been present for approximately 5 weeks. He neither had previous for approximately 5 weeks. He neither had previous history of similar lesions nor did he have a history of history of similar lesions nor did he have a history of cancer or other dermatologic conditions. Physical cancer or other dermatologic conditions. Physical examination demonstrated a 1cm pearly, umbilicated examination demonstrated a 1cm pearly, umbilicated papule with raised borders (papule with raised borders (Figure 1Figure 1).).

Figure 1Clinical picture.

A biopsy (A biopsy (Figure 2Figure 2) showed an asymmetrical nodule with ) showed an asymmetrical nodule with parakeratotic crust and acanthosis with thin epidermal strands parakeratotic crust and acanthosis with thin epidermal strands extending deeply in the underlying dermis. The upper dermis extending deeply in the underlying dermis. The upper dermis showed marked edema and capillary proliferation. The deeper showed marked edema and capillary proliferation. The deeper dermal part of the lesion showed extensive lymphocytic dermal part of the lesion showed extensive lymphocytic infiltration. One red intranuclear inclusion was identified in an infiltration. One red intranuclear inclusion was identified in an epidermal keratinocyte (epidermal keratinocyte (Figure 3Figure 3). ).

Figure 2. Microscopic appearance: raised papule with parakeratotic crust and acanthosis with thin epidermal strands extending deeply in the underlying dermis. The upper dermis is markedly edematous with marked capillary proliferation. The deeper dermal part of the lesion is composed of reactive lymphoid infiltrates.

Figure 3One red intranuclear inclusion in the keratinocyte of the epidermis.

2. What Is Your Diagnosis?2. What Is Your Diagnosis? 2.1. Diagnosis: Human Orf (Ecthyma Contagiosum)2.1. Diagnosis: Human Orf (Ecthyma Contagiosum) Case Synopsis Case Synopsis A 61-year-old sheep farmer presented with a painful A 61-year-old sheep farmer presented with a painful

nonpruritic ulcerated lesion on the left hand that had been nonpruritic ulcerated lesion on the left hand that had been present for approximately 5 weeks. He neither had present for approximately 5 weeks. He neither had previous history of similar lesions nor did he have a history previous history of similar lesions nor did he have a history of cancer or other dermatologic conditions. Physical of cancer or other dermatologic conditions. Physical examination demonstrated a 1cm pearly, umbilicated examination demonstrated a 1cm pearly, umbilicated papule with raised borders (papule with raised borders (Figure 1Figure 1).).

A biopsy (A biopsy (Figure 2Figure 2) showed an asymmetrical nodule with ) showed an asymmetrical nodule with parakeratotic crust and acanthosis with thin epidermal parakeratotic crust and acanthosis with thin epidermal strands extending deeply in the underlying dermis. The strands extending deeply in the underlying dermis. The upper dermis showed marked edema and capillary upper dermis showed marked edema and capillary proliferation. The deeper dermal part of the lesion showed proliferation. The deeper dermal part of the lesion showed extensive lymphocytic infiltration. One red intranuclear extensive lymphocytic infiltration. One red intranuclear inclusion was identified in the epidermal keratinocyte (inclusion was identified in the epidermal keratinocyte (Figure 3Figure 3).).

3. Discussion3. Discussion Our patient was a sheep farmer who presented with a Our patient was a sheep farmer who presented with a

raised umbilicated pearly lesion of his left hand that was raised umbilicated pearly lesion of his left hand that was ulcerated with raised borders. Clinically, it could easily be ulcerated with raised borders. Clinically, it could easily be mistaken for a basal cell carcinoma or squamous cell mistaken for a basal cell carcinoma or squamous cell carcinoma. The central umbilication could also suggest carcinoma. The central umbilication could also suggest keratoacanthoma or a lesion caused by molluscum keratoacanthoma or a lesion caused by molluscum infection though such lesions are usually much smaller. infection though such lesions are usually much smaller. Milker's nodules should be considered too. Both the Milker's nodules should be considered too. Both the clinical history of sheep farming and the microscopic clinical history of sheep farming and the microscopic features including the eosinophilic intranuclear inclusion features including the eosinophilic intranuclear inclusion body in the keratinocyte suggest a diagnosis of human orf body in the keratinocyte suggest a diagnosis of human orf (ecthyma contagiosum). The diagnosis may be further (ecthyma contagiosum). The diagnosis may be further confirmed by electron microscopy done on the fluid confirmed by electron microscopy done on the fluid obtained from the orf lesion showing ovoid cross-hatched obtained from the orf lesion showing ovoid cross-hatched virions [virions [11]. Polymerase chain reaction (PCR), although not ]. Polymerase chain reaction (PCR), although not readily available, can definitely identify orf virus from readily available, can definitely identify orf virus from frozen tissue specimens, vesicle material, or scab debris frozen tissue specimens, vesicle material, or scab debris from orf lesions [from orf lesions [22].].

Ecthyma contagiosum is a zoonotic disease caused by the Ecthyma contagiosum is a zoonotic disease caused by the parapoxvirus that causes “sore mouth” in sheep and goats parapoxvirus that causes “sore mouth” in sheep and goats and orf in human. In ruminants, it is evidenced by and orf in human. In ruminants, it is evidenced by exudative lesions found on the muzzle, eyelids, oral cavity, exudative lesions found on the muzzle, eyelids, oral cavity, feet, or external genitalia. It is more common in younger feet, or external genitalia. It is more common in younger animals. The disease in ruminants is highly contagious to animals. The disease in ruminants is highly contagious to humans and other animals; infected sheep and also humans and other animals; infected sheep and also freshly vaccinated sheep or goats are the source of freshly vaccinated sheep or goats are the source of infection to people. Transmission can be by direct contact infection to people. Transmission can be by direct contact with lesions or indirectly from contaminated object such as with lesions or indirectly from contaminated object such as hair or clothing [hair or clothing [33].].

Parapoxvirus is made up of a dense DNA core surrounded Parapoxvirus is made up of a dense DNA core surrounded by a less dense capsid and 2 narrow electron dense outer by a less dense capsid and 2 narrow electron dense outer layers. After an incubation period of 3–7 days, layers. After an incubation period of 3–7 days, parapoxvirus infections produce 1–3 painful lesions parapoxvirus infections produce 1–3 painful lesions measuring 1-2cm in diameter. During the next 6–8 weeks, measuring 1-2cm in diameter. During the next 6–8 weeks, the lesion passes through 6 clinical stages: maculopapular, the lesion passes through 6 clinical stages: maculopapular, target, acute weeping, nodular, papillomatous, and finally target, acute weeping, nodular, papillomatous, and finally regressive stages [regressive stages [44].].

Microscopically, in the maculopapular stage, there is Microscopically, in the maculopapular stage, there is vacuolization of cells in the upper third of the stratum vacuolization of cells in the upper third of the stratum malpighii leading to multilocular vesicles. Eosinophilic malpighii leading to multilocular vesicles. Eosinophilic intranuclear or cytoplasmic inclusion bodies can be seen. intranuclear or cytoplasmic inclusion bodies can be seen. Vacuolated epidermal cells with inclusion bodies Vacuolated epidermal cells with inclusion bodies characterize the target stage. Ballooning degeneration characterize the target stage. Ballooning degeneration also occurs in the target stage and affects keratinocytes also occurs in the target stage and affects keratinocytes rupture with a tendency to coalesce and produce rupture with a tendency to coalesce and produce reticulated vesicles. Additionally, in the epidermis, there reticulated vesicles. Additionally, in the epidermis, there is an elongation of the rete ridges. Many newly formed is an elongation of the rete ridges. Many newly formed dilated capillaries and a mononuclear infiltrate are dilated capillaries and a mononuclear infiltrate are present in the dermis. This is followed by the acute present in the dermis. This is followed by the acute weeping stage which is characterized by necrosis and a weeping stage which is characterized by necrosis and a massive infiltrate of mononuclear cells throughout the massive infiltrate of mononuclear cells throughout the dermis. Some biopsies of orf may have a marked reactive dermis. Some biopsies of orf may have a marked reactive lymphoid infiltrate with CD30 positive T cells mimicking lymphoid infiltrate with CD30 positive T cells mimicking lymphoma. On progression to the nodular stage, a lymphoma. On progression to the nodular stage, a lichenoid reaction with a high percentage of histiocytes is lichenoid reaction with a high percentage of histiocytes is seen in the skin. In the final papillomatous stage finger-seen in the skin. In the final papillomatous stage finger-like downward projections are displayed in the epidermis like downward projections are displayed in the epidermis along with vasodilatation and chronic inflammation in the along with vasodilatation and chronic inflammation in the dermis. This results in resolution and regression of the dermis. This results in resolution and regression of the lesion [lesion [55]. ].

The natural history of the disease is complete resolution The natural history of the disease is complete resolution and no treatment is indicated. But antiseptic agents to and no treatment is indicated. But antiseptic agents to prevent the superinfection and in some selected cases prevent the superinfection and in some selected cases imiquimod can be applied [imiquimod can be applied [66]. Although, immunity is short ]. Although, immunity is short lived, reinfection frequently appears but no human-to-lived, reinfection frequently appears but no human-to-human transmission occurs. Investigation into prevention human transmission occurs. Investigation into prevention of ecthyma contagiosum in ruminants through vaccination of ecthyma contagiosum in ruminants through vaccination is thought to be the best way to control infection. Vaccines is thought to be the best way to control infection. Vaccines are available that offer some efficacy in sheep but do not are available that offer some efficacy in sheep but do not prevent disease in goats. Research into effective and prevent disease in goats. Research into effective and economical vaccines is ongoing. If infection is controlled in economical vaccines is ongoing. If infection is controlled in the ruminant population, human infection and its economic the ruminant population, human infection and its economic and environmental consequences should decrease [and environmental consequences should decrease [55, , 77].].

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Sarma DPSarma DP, Cox M, Walter P, Crisler W, Huerter C , Cox M, Walter P, Crisler W, Huerter C (2010). A man with an umbilicated papule of the hand: (2010). A man with an umbilicated papule of the hand: what is your diagnosis?. Case Reports in Medicine what is your diagnosis?. Case Reports in Medicine 2010;524021. PMID 20585366 [Pubmed- indexed for 2010;524021. PMID 20585366 [Pubmed- indexed for MEDLINE].MEDLINE].