Mary-Margaret B. Noland, MD

To the Editor:

Lyme disease is caused by spirochetes of the Borrelia burgdorferi sensu lato species complex and transmitted to humans by the bite of the Ixodes scapularis tick. It was first classified as a nationally notifiable disease in 1991, and the incidence has risen remarkably since then.¹ More than 63,000 cases are reported annually to the Centers for Disease Control and Prevention; however, this number reflects severe underreporting, as the true incidence of the disease is projected to be closer to 476,000 cases per year.² Additionally, 95% of US cases occur in the Northeast and upper Midwest.³ Given the pervasiveness of Lyme disease, early and reliable diagnostic methodology is critical, especially in cases in which the timeline of inoculation is unclear. We present a case of Lyme disease that was discovered during a routine dermatologic visit.

A 77-year-old White man with no relevant medical history presented to a dermatology clinic in west-central Virginia for a routine skin check. Physical examination revealed a well-appearing patient without overt skin abnormalities. However, on closer evaluation, a ­0.2×0.1-cm engorged black I scapularis tick was visualized on the left lateral upper back. There was a surrounding zone of erythema that measured less than the 5-cm-diameter criterion for erythema migrans.¹

Upon questioning, the patient reported that he was unaware of the tick and could not provide a timeline for inoculation. To ensure proper treatment, the tick was removed in the office and a specimen was sent for histopathology. The arthropod was formalin fixed and paraffin embedded, and it was examined using hematoxylin and eosin and Warthin-Starry stains. Histopathology of the specimen revealed a blood-engorged arthropod. Warthin-Starry stain of the abdomen of the tick highlighted tiny strandlike spirochetes within the gut that were compatible with B burgdorferi (Figure). This finding prompted treatment with a 3-week course of doxycycline. Following treatment, erythema resolved. The patient experienced no sequelae.

Lyme disease can cause a range of serious complications if left untreated, including arthritis, neurologic deficits, and heart block. During the early stages of disease, the sensitivity and specificity of diagnostic methods such as serologic testing are limited.⁴ The gold standard for the diagnosis of Lyme disease comprises culture and subsequent confirmation by polymerase chain reaction.¹ However, cultivation of B burgdorferi is challenging.⁵ The Centers for Disease Control and Prevention recommends 2-tiered serologic antibody analysis, which has 27% sensitivity during the first week of cutaneous symptoms, and involves an enzyme-linked immunoassay followed by reflexive immunoblotting for positive or indeterminate cases.^2,6 The precision of this method is limited by several variables; for example, seroconversion fails to occur in approximately 40% of cases, even after proven exposure to the spirochete.⁷ Furthermore, the sensitivity of the test is particularly low during the first 4 to 6 weeks of infection—before the body mounts a proper immune response; fewer than 50% of patients exhibit a positive response to the test at initial presentation.³

Clinical diagnosis of Lyme disease is possible, though the pathognomonic erythema migrans rash can be delayed for as long as 30 days and remains absent in 20% to 30% of patients.¹ Prophylactic treatment can be offered to individuals who reside in a hyperendemic area and have a rash or have had an engorged Ixodes tick attached for longer than 36 hours.⁸

More definitive techniques for early diagnosis are needed to enable selective and accurate treatment. The standard of care for Lyme disease includes a 10-day course of doxycycline or a 14-day course of cefuroxime axetil or amoxicillin.⁹ Many patients tolerate treatment and achieve resolution of disease, but antibiotics are not benign, as some patients experience drug-related adverse effects such as photosensitivity, urticaria, diarrhea, nausea, vomiting, esophagitis, hepatotoxicity, and the Jarisch-Herxheimer reaction (fever, chills, rigors, nausea and vomiting, headache, tachycardia, hypotension, hyperventilation, flushing, myalgia, and exacerbation of lesions).^10,11 In a group of 123 patients with Lyme disease, 30% treated with cefuroxime axetil and 32% treated with doxycycline had 1 or more drug-related adverse events.¹⁰ Additionally, avoidable antibiotic use is associated with increasing antibiotic resistance.¹² Improved diagnostic accuracy would prevent unnecessary treatment. Galan and colleagues⁷ reported that Warthin-Starry staining of prepared sections of the abdomen of a tick allowed for detection of B burgdorferi with a sensitivity of 71% and specificity of 83%. This technique did not delay the final biopsy report and may be a promising adjunct to the diagnosis of early Lyme disease.⁷

Anecdotally, many patients who present with an attached and engorged tick are unaware of the timeline of their exposure. Histologic analysis of a removed tick could aid in early clinical decision-making—ie, when the diagnosis is unclear and treatment guidelines vary by region and circumstance. Improved sensitivity and specificity of diagnosis can prevent unnecessary antibiotic treatment, which is associated with adverse effects and escalation of antibiotic resistance.

To the Editor:

Lyme disease is caused by spirochetes of the Borrelia burgdorferi sensu lato species complex and transmitted to humans by the bite of the Ixodes scapularis tick. It was first classified as a nationally notifiable disease in 1991, and the incidence has risen remarkably since then.¹ More than 63,000 cases are reported annually to the Centers for Disease Control and Prevention; however, this number reflects severe underreporting, as the true incidence of the disease is projected to be closer to 476,000 cases per year.² Additionally, 95% of US cases occur in the Northeast and upper Midwest.³ Given the pervasiveness of Lyme disease, early and reliable diagnostic methodology is critical, especially in cases in which the timeline of inoculation is unclear. We present a case of Lyme disease that was discovered during a routine dermatologic visit.

A 77-year-old White man with no relevant medical history presented to a dermatology clinic in west-central Virginia for a routine skin check. Physical examination revealed a well-appearing patient without overt skin abnormalities. However, on closer evaluation, a ­0.2×0.1-cm engorged black I scapularis tick was visualized on the left lateral upper back. There was a surrounding zone of erythema that measured less than the 5-cm-diameter criterion for erythema migrans.¹

Upon questioning, the patient reported that he was unaware of the tick and could not provide a timeline for inoculation. To ensure proper treatment, the tick was removed in the office and a specimen was sent for histopathology. The arthropod was formalin fixed and paraffin embedded, and it was examined using hematoxylin and eosin and Warthin-Starry stains. Histopathology of the specimen revealed a blood-engorged arthropod. Warthin-Starry stain of the abdomen of the tick highlighted tiny strandlike spirochetes within the gut that were compatible with B burgdorferi (Figure). This finding prompted treatment with a 3-week course of doxycycline. Following treatment, erythema resolved. The patient experienced no sequelae.

Lyme disease can cause a range of serious complications if left untreated, including arthritis, neurologic deficits, and heart block. During the early stages of disease, the sensitivity and specificity of diagnostic methods such as serologic testing are limited.⁴ The gold standard for the diagnosis of Lyme disease comprises culture and subsequent confirmation by polymerase chain reaction.¹ However, cultivation of B burgdorferi is challenging.⁵ The Centers for Disease Control and Prevention recommends 2-tiered serologic antibody analysis, which has 27% sensitivity during the first week of cutaneous symptoms, and involves an enzyme-linked immunoassay followed by reflexive immunoblotting for positive or indeterminate cases.^2,6 The precision of this method is limited by several variables; for example, seroconversion fails to occur in approximately 40% of cases, even after proven exposure to the spirochete.⁷ Furthermore, the sensitivity of the test is particularly low during the first 4 to 6 weeks of infection—before the body mounts a proper immune response; fewer than 50% of patients exhibit a positive response to the test at initial presentation.³

Clinical diagnosis of Lyme disease is possible, though the pathognomonic erythema migrans rash can be delayed for as long as 30 days and remains absent in 20% to 30% of patients.¹ Prophylactic treatment can be offered to individuals who reside in a hyperendemic area and have a rash or have had an engorged Ixodes tick attached for longer than 36 hours.⁸

More definitive techniques for early diagnosis are needed to enable selective and accurate treatment. The standard of care for Lyme disease includes a 10-day course of doxycycline or a 14-day course of cefuroxime axetil or amoxicillin.⁹ Many patients tolerate treatment and achieve resolution of disease, but antibiotics are not benign, as some patients experience drug-related adverse effects such as photosensitivity, urticaria, diarrhea, nausea, vomiting, esophagitis, hepatotoxicity, and the Jarisch-Herxheimer reaction (fever, chills, rigors, nausea and vomiting, headache, tachycardia, hypotension, hyperventilation, flushing, myalgia, and exacerbation of lesions).^10,11 In a group of 123 patients with Lyme disease, 30% treated with cefuroxime axetil and 32% treated with doxycycline had 1 or more drug-related adverse events.¹⁰ Additionally, avoidable antibiotic use is associated with increasing antibiotic resistance.¹² Improved diagnostic accuracy would prevent unnecessary treatment. Galan and colleagues⁷ reported that Warthin-Starry staining of prepared sections of the abdomen of a tick allowed for detection of B burgdorferi with a sensitivity of 71% and specificity of 83%. This technique did not delay the final biopsy report and may be a promising adjunct to the diagnosis of early Lyme disease.⁷

Anecdotally, many patients who present with an attached and engorged tick are unaware of the timeline of their exposure. Histologic analysis of a removed tick could aid in early clinical decision-making—ie, when the diagnosis is unclear and treatment guidelines vary by region and circumstance. Improved sensitivity and specificity of diagnosis can prevent unnecessary antibiotic treatment, which is associated with adverse effects and escalation of antibiotic resistance.

To the Editor:

Lyme disease is caused by spirochetes of the Borrelia burgdorferi sensu lato species complex and transmitted to humans by the bite of the Ixodes scapularis tick. It was first classified as a nationally notifiable disease in 1991, and the incidence has risen remarkably since then.¹ More than 63,000 cases are reported annually to the Centers for Disease Control and Prevention; however, this number reflects severe underreporting, as the true incidence of the disease is projected to be closer to 476,000 cases per year.² Additionally, 95% of US cases occur in the Northeast and upper Midwest.³ Given the pervasiveness of Lyme disease, early and reliable diagnostic methodology is critical, especially in cases in which the timeline of inoculation is unclear. We present a case of Lyme disease that was discovered during a routine dermatologic visit.

A 77-year-old White man with no relevant medical history presented to a dermatology clinic in west-central Virginia for a routine skin check. Physical examination revealed a well-appearing patient without overt skin abnormalities. However, on closer evaluation, a ­0.2×0.1-cm engorged black I scapularis tick was visualized on the left lateral upper back. There was a surrounding zone of erythema that measured less than the 5-cm-diameter criterion for erythema migrans.¹

Upon questioning, the patient reported that he was unaware of the tick and could not provide a timeline for inoculation. To ensure proper treatment, the tick was removed in the office and a specimen was sent for histopathology. The arthropod was formalin fixed and paraffin embedded, and it was examined using hematoxylin and eosin and Warthin-Starry stains. Histopathology of the specimen revealed a blood-engorged arthropod. Warthin-Starry stain of the abdomen of the tick highlighted tiny strandlike spirochetes within the gut that were compatible with B burgdorferi (Figure). This finding prompted treatment with a 3-week course of doxycycline. Following treatment, erythema resolved. The patient experienced no sequelae.

Lyme disease can cause a range of serious complications if left untreated, including arthritis, neurologic deficits, and heart block. During the early stages of disease, the sensitivity and specificity of diagnostic methods such as serologic testing are limited.⁴ The gold standard for the diagnosis of Lyme disease comprises culture and subsequent confirmation by polymerase chain reaction.¹ However, cultivation of B burgdorferi is challenging.⁵ The Centers for Disease Control and Prevention recommends 2-tiered serologic antibody analysis, which has 27% sensitivity during the first week of cutaneous symptoms, and involves an enzyme-linked immunoassay followed by reflexive immunoblotting for positive or indeterminate cases.^2,6 The precision of this method is limited by several variables; for example, seroconversion fails to occur in approximately 40% of cases, even after proven exposure to the spirochete.⁷ Furthermore, the sensitivity of the test is particularly low during the first 4 to 6 weeks of infection—before the body mounts a proper immune response; fewer than 50% of patients exhibit a positive response to the test at initial presentation.³

Clinical diagnosis of Lyme disease is possible, though the pathognomonic erythema migrans rash can be delayed for as long as 30 days and remains absent in 20% to 30% of patients.¹ Prophylactic treatment can be offered to individuals who reside in a hyperendemic area and have a rash or have had an engorged Ixodes tick attached for longer than 36 hours.⁸

More definitive techniques for early diagnosis are needed to enable selective and accurate treatment. The standard of care for Lyme disease includes a 10-day course of doxycycline or a 14-day course of cefuroxime axetil or amoxicillin.⁹ Many patients tolerate treatment and achieve resolution of disease, but antibiotics are not benign, as some patients experience drug-related adverse effects such as photosensitivity, urticaria, diarrhea, nausea, vomiting, esophagitis, hepatotoxicity, and the Jarisch-Herxheimer reaction (fever, chills, rigors, nausea and vomiting, headache, tachycardia, hypotension, hyperventilation, flushing, myalgia, and exacerbation of lesions).^10,11 In a group of 123 patients with Lyme disease, 30% treated with cefuroxime axetil and 32% treated with doxycycline had 1 or more drug-related adverse events.¹⁰ Additionally, avoidable antibiotic use is associated with increasing antibiotic resistance.¹² Improved diagnostic accuracy would prevent unnecessary treatment. Galan and colleagues⁷ reported that Warthin-Starry staining of prepared sections of the abdomen of a tick allowed for detection of B burgdorferi with a sensitivity of 71% and specificity of 83%. This technique did not delay the final biopsy report and may be a promising adjunct to the diagnosis of early Lyme disease.⁷

Anecdotally, many patients who present with an attached and engorged tick are unaware of the timeline of their exposure. Histologic analysis of a removed tick could aid in early clinical decision-making—ie, when the diagnosis is unclear and treatment guidelines vary by region and circumstance. Improved sensitivity and specificity of diagnosis can prevent unnecessary antibiotic treatment, which is associated with adverse effects and escalation of antibiotic resistance.

The Diagnosis: Atypical Mycobacterial Infection

The history of rapid growth followed by shrinkage as well as the craterlike clinical appearance of our patient’s lesion were suspicious for the keratoacanthoma variant of squamous cell carcinoma (SCC). Periodic acid–Schiff green staining was negative for fungal or bacterial organisms, and the biopsy findings of keratinocyte atypia and irregular epidermal proliferation seemed to confirm our suspicion for well-differentiated SCC (Figure 1). Our patient subsequently was scheduled for Mohs micrographic surgery. Fortunately, a sample of tissue had been sent for panculture—bacterial, fungal, and mycobacterial—to rule out infectious etiologies, given the history of possible traumatic inoculation, and returned positive for Mycobacterium marinum infection prior to the surgery. Mohs surgery was canceled, and he was referred to an infectious disease specialist who started antibiotic treatment with azithromycin, ethambutol, and rifabutin. After 1 month of treatment the lesion substantially improved (Figure 2), further supporting the diagnosis of M marinum infection over SCC.

The differential diagnosis also included sporotrichosis, leishmaniasis, and chromoblastomycosis. Sporotrichosis lesions typically develop as multiple nodules and ulcers along a path of lymphatic drainage and can exhibit asteroid bodies and cigar-shaped yeast forms on histology. Chromoblastomycosis may display pseudoepitheliomatous hyperplasia and granulomatous inflammation; however, pathognomonic pigmented Medlar bodies also likely would be present.¹ Leishmaniasis has a wide variety of presentations; however, it typically occurs in patients with exposure to endemic areas outside of the United States. Although leishmaniasis may demonstrate pseudoepitheliomatous hyperplasia, ulceration, and mixed inflammation on histology, it also likely would show amastigotes within dermal macrophages.²

Atypical mycobacterial infections initially may be misdiagnosed as SCC due to their tendency to induce irregular acanthosis in the form of pseudoepitheliomatous hyperplasia as well as mild keratinocyte atypia secondary to inflammation.^3,4 Our case is unique because it occurred with M marinum infection specifically. The histopathologic findings of M marinum infections are variable and may additionally include granulomas, most commonly suppurative; intraepithelial abscesses; small vessel proliferation; dermal fibrosis; multinucleated giant cells; and transepidermal elimination.^4,5 Periodic acid–Schiff, Ziehl-Neelsen (acid-fast bacilli), and Fite staining may be used to distinguish M marinum infection from SCC but have low sensitivities (approximately 30%). Culture remains the most reliable test, with a sensitivity of nearly 80%.^5-7 In our patient, a Periodic acid–Schiff stain was obtained prior to receiving culture results, and acid-fast bacilli and Fite staining were added after the culture returned positive; however, all 3 stains failed to highlight any mycobacteria.

The primary risk factor for infection with M marinum is contact with aquatic environments or marine animals, and most cases involve the fingers or the hand.⁶ After we reached the diagnosis and further discussed the patient’s history, he recalled fishing for and cleaning raw shrimp around the time that he had a splinter. The Infectious Diseases Society of America recommends a treatment course extending 1 to 2 months after clinical symptoms resolve with ethambutol in addition to clarithromycin or azithromycin.⁸ If the infection is near a joint, rifampin should be empirically added to account for a potentially deeper infection. Imaging should be obtained to evaluate for joint space involvement, with magnetic resonance imaging being the preferred modality. If joint space involvement is confirmed, surgical debridement is indicated. Surgical debridement also is indicated for infections that fail to respond to antibiotic therapy.⁸

This case highlights M marinum infection as a potential mimicker of SCC, particularly if the biopsy is relatively superficial, as often occurs when obtained via the common shave technique. The distinction is critical, as M marinum infection is highly treatable and inappropriate surgery on the typical hand and finger locations may subject patients to substantial morbidity, such as the need for a skin graft, reduced mobility from scarring, or risk for serious wound infection.⁹ For superficial biopsies of an atypical squamous process, pathologists also may consider routinely recommending tissue culture, especially for hand and finger locations or when a history of local trauma is reported, instead of recommending complete excision or repeat biopsy alone.

The Diagnosis: Atypical Mycobacterial Infection

The history of rapid growth followed by shrinkage as well as the craterlike clinical appearance of our patient’s lesion were suspicious for the keratoacanthoma variant of squamous cell carcinoma (SCC). Periodic acid–Schiff green staining was negative for fungal or bacterial organisms, and the biopsy findings of keratinocyte atypia and irregular epidermal proliferation seemed to confirm our suspicion for well-differentiated SCC (Figure 1). Our patient subsequently was scheduled for Mohs micrographic surgery. Fortunately, a sample of tissue had been sent for panculture—bacterial, fungal, and mycobacterial—to rule out infectious etiologies, given the history of possible traumatic inoculation, and returned positive for Mycobacterium marinum infection prior to the surgery. Mohs surgery was canceled, and he was referred to an infectious disease specialist who started antibiotic treatment with azithromycin, ethambutol, and rifabutin. After 1 month of treatment the lesion substantially improved (Figure 2), further supporting the diagnosis of M marinum infection over SCC.

The differential diagnosis also included sporotrichosis, leishmaniasis, and chromoblastomycosis. Sporotrichosis lesions typically develop as multiple nodules and ulcers along a path of lymphatic drainage and can exhibit asteroid bodies and cigar-shaped yeast forms on histology. Chromoblastomycosis may display pseudoepitheliomatous hyperplasia and granulomatous inflammation; however, pathognomonic pigmented Medlar bodies also likely would be present.¹ Leishmaniasis has a wide variety of presentations; however, it typically occurs in patients with exposure to endemic areas outside of the United States. Although leishmaniasis may demonstrate pseudoepitheliomatous hyperplasia, ulceration, and mixed inflammation on histology, it also likely would show amastigotes within dermal macrophages.²

Atypical mycobacterial infections initially may be misdiagnosed as SCC due to their tendency to induce irregular acanthosis in the form of pseudoepitheliomatous hyperplasia as well as mild keratinocyte atypia secondary to inflammation.^3,4 Our case is unique because it occurred with M marinum infection specifically. The histopathologic findings of M marinum infections are variable and may additionally include granulomas, most commonly suppurative; intraepithelial abscesses; small vessel proliferation; dermal fibrosis; multinucleated giant cells; and transepidermal elimination.^4,5 Periodic acid–Schiff, Ziehl-Neelsen (acid-fast bacilli), and Fite staining may be used to distinguish M marinum infection from SCC but have low sensitivities (approximately 30%). Culture remains the most reliable test, with a sensitivity of nearly 80%.^5-7 In our patient, a Periodic acid–Schiff stain was obtained prior to receiving culture results, and acid-fast bacilli and Fite staining were added after the culture returned positive; however, all 3 stains failed to highlight any mycobacteria.

The primary risk factor for infection with M marinum is contact with aquatic environments or marine animals, and most cases involve the fingers or the hand.⁶ After we reached the diagnosis and further discussed the patient’s history, he recalled fishing for and cleaning raw shrimp around the time that he had a splinter. The Infectious Diseases Society of America recommends a treatment course extending 1 to 2 months after clinical symptoms resolve with ethambutol in addition to clarithromycin or azithromycin.⁸ If the infection is near a joint, rifampin should be empirically added to account for a potentially deeper infection. Imaging should be obtained to evaluate for joint space involvement, with magnetic resonance imaging being the preferred modality. If joint space involvement is confirmed, surgical debridement is indicated. Surgical debridement also is indicated for infections that fail to respond to antibiotic therapy.⁸

This case highlights M marinum infection as a potential mimicker of SCC, particularly if the biopsy is relatively superficial, as often occurs when obtained via the common shave technique. The distinction is critical, as M marinum infection is highly treatable and inappropriate surgery on the typical hand and finger locations may subject patients to substantial morbidity, such as the need for a skin graft, reduced mobility from scarring, or risk for serious wound infection.⁹ For superficial biopsies of an atypical squamous process, pathologists also may consider routinely recommending tissue culture, especially for hand and finger locations or when a history of local trauma is reported, instead of recommending complete excision or repeat biopsy alone.

The Diagnosis: Atypical Mycobacterial Infection

The history of rapid growth followed by shrinkage as well as the craterlike clinical appearance of our patient’s lesion were suspicious for the keratoacanthoma variant of squamous cell carcinoma (SCC). Periodic acid–Schiff green staining was negative for fungal or bacterial organisms, and the biopsy findings of keratinocyte atypia and irregular epidermal proliferation seemed to confirm our suspicion for well-differentiated SCC (Figure 1). Our patient subsequently was scheduled for Mohs micrographic surgery. Fortunately, a sample of tissue had been sent for panculture—bacterial, fungal, and mycobacterial—to rule out infectious etiologies, given the history of possible traumatic inoculation, and returned positive for Mycobacterium marinum infection prior to the surgery. Mohs surgery was canceled, and he was referred to an infectious disease specialist who started antibiotic treatment with azithromycin, ethambutol, and rifabutin. After 1 month of treatment the lesion substantially improved (Figure 2), further supporting the diagnosis of M marinum infection over SCC.

The differential diagnosis also included sporotrichosis, leishmaniasis, and chromoblastomycosis. Sporotrichosis lesions typically develop as multiple nodules and ulcers along a path of lymphatic drainage and can exhibit asteroid bodies and cigar-shaped yeast forms on histology. Chromoblastomycosis may display pseudoepitheliomatous hyperplasia and granulomatous inflammation; however, pathognomonic pigmented Medlar bodies also likely would be present.¹ Leishmaniasis has a wide variety of presentations; however, it typically occurs in patients with exposure to endemic areas outside of the United States. Although leishmaniasis may demonstrate pseudoepitheliomatous hyperplasia, ulceration, and mixed inflammation on histology, it also likely would show amastigotes within dermal macrophages.²

Atypical mycobacterial infections initially may be misdiagnosed as SCC due to their tendency to induce irregular acanthosis in the form of pseudoepitheliomatous hyperplasia as well as mild keratinocyte atypia secondary to inflammation.^3,4 Our case is unique because it occurred with M marinum infection specifically. The histopathologic findings of M marinum infections are variable and may additionally include granulomas, most commonly suppurative; intraepithelial abscesses; small vessel proliferation; dermal fibrosis; multinucleated giant cells; and transepidermal elimination.^4,5 Periodic acid–Schiff, Ziehl-Neelsen (acid-fast bacilli), and Fite staining may be used to distinguish M marinum infection from SCC but have low sensitivities (approximately 30%). Culture remains the most reliable test, with a sensitivity of nearly 80%.^5-7 In our patient, a Periodic acid–Schiff stain was obtained prior to receiving culture results, and acid-fast bacilli and Fite staining were added after the culture returned positive; however, all 3 stains failed to highlight any mycobacteria.

The primary risk factor for infection with M marinum is contact with aquatic environments or marine animals, and most cases involve the fingers or the hand.⁶ After we reached the diagnosis and further discussed the patient’s history, he recalled fishing for and cleaning raw shrimp around the time that he had a splinter. The Infectious Diseases Society of America recommends a treatment course extending 1 to 2 months after clinical symptoms resolve with ethambutol in addition to clarithromycin or azithromycin.⁸ If the infection is near a joint, rifampin should be empirically added to account for a potentially deeper infection. Imaging should be obtained to evaluate for joint space involvement, with magnetic resonance imaging being the preferred modality. If joint space involvement is confirmed, surgical debridement is indicated. Surgical debridement also is indicated for infections that fail to respond to antibiotic therapy.⁸

This case highlights M marinum infection as a potential mimicker of SCC, particularly if the biopsy is relatively superficial, as often occurs when obtained via the common shave technique. The distinction is critical, as M marinum infection is highly treatable and inappropriate surgery on the typical hand and finger locations may subject patients to substantial morbidity, such as the need for a skin graft, reduced mobility from scarring, or risk for serious wound infection.⁹ For superficial biopsies of an atypical squamous process, pathologists also may consider routinely recommending tissue culture, especially for hand and finger locations or when a history of local trauma is reported, instead of recommending complete excision or repeat biopsy alone.

Case Reports

Patient 1
A 65-year-old woman presented to the dermatology clinic in July with a pruritic rash of 2 days’ duration that started on the back and spread diffusely. The patient gardened regularly. Physical examination showed inflammatory papules and pustules on the back (Figure 1), as well as the groin, breasts, and ears. There was a punctate black dot in the center of some papules, and dermoscopy revealed ticks (Figure 2). Removal and microscopic examination confirmed larval-stage lone star ticks (Figure 3). The patient was prescribed topical steroids for pruritus as well as oral doxycycline for prophylaxis against tick-borne illnesses.

Patient 2
A 54-year-old man presented to the same clinic in July with pruritic lesions on the back, legs, ankles, and scrotum of 3 days’ duration that first appeared 24 hours after performing yardwork. Physical examination revealed diffusely distributed papules, pustules, and vesicles on the back (Figure 4). Some papules featured a punctate black dot in the center (similar to patient 1), and dermoscopy again revealed ticks. Removal and microscopic examination confirmed larval-stage ticks. The patient was treated with topical steroids and oral antihistamines for pruritus as well as prophylactic oral doxycycline.

Comment

Ticks are well-known human parasites, representing the second most common vector of human infectious disease.¹ Ticks have 3 motile stages: larva (or “seed”), nymph, and adult. They can bite humans during all stages. Larval ticks, distinguished by having 6 legs rather than 8 legs in nymphs and adults, can attack in droves and cause an infestation that presents as diffuse, pruritic, erythematous papules and pustules.^2-4 The first report of larval tick infestation in humans may have been in 1728 by William Byrd who described finding ticks on the skin that were too small to see without a microscope.⁵

Identification
The ticks in both of our cases were lone star ticks (Amblyomma americanum). The larval stage of A americanum is a proven cause of cutaneous reaction.^6,7 A PubMed search of articles indexed for MEDLINE as well as a Google Scholar search using the terms tick, seed tick, or tick bite in combination with rash, eruption, infestation, papule, pustule, or pruritic revealed 6 reported cases of larval tick infestation in the literature (including our case); 5 were caused by A americanum and 1 by Ixodes dammini (now known as Ixodes scapularis); all occurred in July or August.^3,7-10 This time frame is consistent with the general tick life cycle across species: Adults feed from April to June, then lay eggs that hatch into larval ticks within 4 to 6 weeks. After hatching, larval ticks climb grass and weeds awaiting a passing host.⁴

Diagnosis
Larval tick infestation remains a frequently misdiagnosed etiology of diffuse pruritic papules and pustules, especially in urban settings where physicians are less likely to be familiar with this type of manifestation.^3,9-11 Larval ticks are submillimeter in size and difficult to appreciate with the naked eye, contributing to misdiagnosis. A punctate black dot may sometimes be seen in papules; however, dermoscopy is critical for accurate diagnosis, as hemorrhagic crust is a frequent misdiagnosis.

Management
In addition to symptomatic therapy, both of our patients received doxycycline as antibiotic prophylaxis for tick-borne illnesses given that a high number of ticks had been attached for more than 2 days.^12,13 Antibiotic prophylaxis for tick-borne illness is controversial. The exception is Lyme disease transmitted by nymphal or adult I scapularis when specific conditions are met: the bite must have occurred in an endemic area, doxycycline cannot be contraindicated, estimated duration of attachment is at least 36 hours, and prophylaxis must be started within 72 hours of tick removal.¹³ There are no official recommendations for the A americanum species or for larval-stage ticks of any species. Larval-stage ticks acting as vectors for disease transmission is not well documented in recent literature, and there currently is limited evidence supporting prophylactic antibiotics for larval tick bites. The presence of spotted fever rickettsioses has been reported (with the exception of Rickettsia rickettsii and Ehrlichia chaffeensis) in larval A americanum ticks, suggesting a theoretical possibility that they could act as disease vectors.^3,8,11,14-17 At a minimum, both prompt tick removal and close patient follow-up is warranted.

Conclusion

Human infestation with larval ticks is a common occurrence but can present a diagnostic challenge to an unfamiliar physician. We encourage consideration of larval tick infestation as the etiology of multiple or diffuse pruritic papules with a history of outdoor exposure.

Case Reports

Patient 1
A 65-year-old woman presented to the dermatology clinic in July with a pruritic rash of 2 days’ duration that started on the back and spread diffusely. The patient gardened regularly. Physical examination showed inflammatory papules and pustules on the back (Figure 1), as well as the groin, breasts, and ears. There was a punctate black dot in the center of some papules, and dermoscopy revealed ticks (Figure 2). Removal and microscopic examination confirmed larval-stage lone star ticks (Figure 3). The patient was prescribed topical steroids for pruritus as well as oral doxycycline for prophylaxis against tick-borne illnesses.

Patient 2
A 54-year-old man presented to the same clinic in July with pruritic lesions on the back, legs, ankles, and scrotum of 3 days’ duration that first appeared 24 hours after performing yardwork. Physical examination revealed diffusely distributed papules, pustules, and vesicles on the back (Figure 4). Some papules featured a punctate black dot in the center (similar to patient 1), and dermoscopy again revealed ticks. Removal and microscopic examination confirmed larval-stage ticks. The patient was treated with topical steroids and oral antihistamines for pruritus as well as prophylactic oral doxycycline.

Comment

Ticks are well-known human parasites, representing the second most common vector of human infectious disease.¹ Ticks have 3 motile stages: larva (or “seed”), nymph, and adult. They can bite humans during all stages. Larval ticks, distinguished by having 6 legs rather than 8 legs in nymphs and adults, can attack in droves and cause an infestation that presents as diffuse, pruritic, erythematous papules and pustules.^2-4 The first report of larval tick infestation in humans may have been in 1728 by William Byrd who described finding ticks on the skin that were too small to see without a microscope.⁵

Identification
The ticks in both of our cases were lone star ticks (Amblyomma americanum). The larval stage of A americanum is a proven cause of cutaneous reaction.^6,7 A PubMed search of articles indexed for MEDLINE as well as a Google Scholar search using the terms tick, seed tick, or tick bite in combination with rash, eruption, infestation, papule, pustule, or pruritic revealed 6 reported cases of larval tick infestation in the literature (including our case); 5 were caused by A americanum and 1 by Ixodes dammini (now known as Ixodes scapularis); all occurred in July or August.^3,7-10 This time frame is consistent with the general tick life cycle across species: Adults feed from April to June, then lay eggs that hatch into larval ticks within 4 to 6 weeks. After hatching, larval ticks climb grass and weeds awaiting a passing host.⁴

Diagnosis
Larval tick infestation remains a frequently misdiagnosed etiology of diffuse pruritic papules and pustules, especially in urban settings where physicians are less likely to be familiar with this type of manifestation.^3,9-11 Larval ticks are submillimeter in size and difficult to appreciate with the naked eye, contributing to misdiagnosis. A punctate black dot may sometimes be seen in papules; however, dermoscopy is critical for accurate diagnosis, as hemorrhagic crust is a frequent misdiagnosis.

Management
In addition to symptomatic therapy, both of our patients received doxycycline as antibiotic prophylaxis for tick-borne illnesses given that a high number of ticks had been attached for more than 2 days.^12,13 Antibiotic prophylaxis for tick-borne illness is controversial. The exception is Lyme disease transmitted by nymphal or adult I scapularis when specific conditions are met: the bite must have occurred in an endemic area, doxycycline cannot be contraindicated, estimated duration of attachment is at least 36 hours, and prophylaxis must be started within 72 hours of tick removal.¹³ There are no official recommendations for the A americanum species or for larval-stage ticks of any species. Larval-stage ticks acting as vectors for disease transmission is not well documented in recent literature, and there currently is limited evidence supporting prophylactic antibiotics for larval tick bites. The presence of spotted fever rickettsioses has been reported (with the exception of Rickettsia rickettsii and Ehrlichia chaffeensis) in larval A americanum ticks, suggesting a theoretical possibility that they could act as disease vectors.^3,8,11,14-17 At a minimum, both prompt tick removal and close patient follow-up is warranted.

Conclusion

Human infestation with larval ticks is a common occurrence but can present a diagnostic challenge to an unfamiliar physician. We encourage consideration of larval tick infestation as the etiology of multiple or diffuse pruritic papules with a history of outdoor exposure.

Case Reports

Patient 1
A 65-year-old woman presented to the dermatology clinic in July with a pruritic rash of 2 days’ duration that started on the back and spread diffusely. The patient gardened regularly. Physical examination showed inflammatory papules and pustules on the back (Figure 1), as well as the groin, breasts, and ears. There was a punctate black dot in the center of some papules, and dermoscopy revealed ticks (Figure 2). Removal and microscopic examination confirmed larval-stage lone star ticks (Figure 3). The patient was prescribed topical steroids for pruritus as well as oral doxycycline for prophylaxis against tick-borne illnesses.

Patient 2
A 54-year-old man presented to the same clinic in July with pruritic lesions on the back, legs, ankles, and scrotum of 3 days’ duration that first appeared 24 hours after performing yardwork. Physical examination revealed diffusely distributed papules, pustules, and vesicles on the back (Figure 4). Some papules featured a punctate black dot in the center (similar to patient 1), and dermoscopy again revealed ticks. Removal and microscopic examination confirmed larval-stage ticks. The patient was treated with topical steroids and oral antihistamines for pruritus as well as prophylactic oral doxycycline.

Comment

Ticks are well-known human parasites, representing the second most common vector of human infectious disease.¹ Ticks have 3 motile stages: larva (or “seed”), nymph, and adult. They can bite humans during all stages. Larval ticks, distinguished by having 6 legs rather than 8 legs in nymphs and adults, can attack in droves and cause an infestation that presents as diffuse, pruritic, erythematous papules and pustules.^2-4 The first report of larval tick infestation in humans may have been in 1728 by William Byrd who described finding ticks on the skin that were too small to see without a microscope.⁵

Identification
The ticks in both of our cases were lone star ticks (Amblyomma americanum). The larval stage of A americanum is a proven cause of cutaneous reaction.^6,7 A PubMed search of articles indexed for MEDLINE as well as a Google Scholar search using the terms tick, seed tick, or tick bite in combination with rash, eruption, infestation, papule, pustule, or pruritic revealed 6 reported cases of larval tick infestation in the literature (including our case); 5 were caused by A americanum and 1 by Ixodes dammini (now known as Ixodes scapularis); all occurred in July or August.^3,7-10 This time frame is consistent with the general tick life cycle across species: Adults feed from April to June, then lay eggs that hatch into larval ticks within 4 to 6 weeks. After hatching, larval ticks climb grass and weeds awaiting a passing host.⁴

Diagnosis
Larval tick infestation remains a frequently misdiagnosed etiology of diffuse pruritic papules and pustules, especially in urban settings where physicians are less likely to be familiar with this type of manifestation.^3,9-11 Larval ticks are submillimeter in size and difficult to appreciate with the naked eye, contributing to misdiagnosis. A punctate black dot may sometimes be seen in papules; however, dermoscopy is critical for accurate diagnosis, as hemorrhagic crust is a frequent misdiagnosis.

Management
In addition to symptomatic therapy, both of our patients received doxycycline as antibiotic prophylaxis for tick-borne illnesses given that a high number of ticks had been attached for more than 2 days.^12,13 Antibiotic prophylaxis for tick-borne illness is controversial. The exception is Lyme disease transmitted by nymphal or adult I scapularis when specific conditions are met: the bite must have occurred in an endemic area, doxycycline cannot be contraindicated, estimated duration of attachment is at least 36 hours, and prophylaxis must be started within 72 hours of tick removal.¹³ There are no official recommendations for the A americanum species or for larval-stage ticks of any species. Larval-stage ticks acting as vectors for disease transmission is not well documented in recent literature, and there currently is limited evidence supporting prophylactic antibiotics for larval tick bites. The presence of spotted fever rickettsioses has been reported (with the exception of Rickettsia rickettsii and Ehrlichia chaffeensis) in larval A americanum ticks, suggesting a theoretical possibility that they could act as disease vectors.^3,8,11,14-17 At a minimum, both prompt tick removal and close patient follow-up is warranted.

Conclusion

Human infestation with larval ticks is a common occurrence but can present a diagnostic challenge to an unfamiliar physician. We encourage consideration of larval tick infestation as the etiology of multiple or diffuse pruritic papules with a history of outdoor exposure.