Cutis

To the Editor:

Acute generalized exanthematous pustulosis (AGEP) is an acute skin reaction that is characterized by generalized, nonfollicular, pinhead-sized, sterile pustules on an erythematous and edematous background. The eruption can be accompanied by fever and neutrophilic leukocytosis. Skin symptoms arise quickly (within a few hours), most commonly following drug administration. The medications most frequently responsible are beta-lactam antibiotics, macrolides, calcium channel blockers, and antimalarials. Pustules spontaneously resolve in 15 days and generalized desquamation occurs approximately 2 weeks later. The estimated incidence rate of AGEP is approximately 1 to 5 cases per million per year. Acute localized exanthematous pustulosis (ALEP) is a less common form of AGEP. We report a case of ALEP localized on the face that was caused by flurbiprofen, a propionic acid derivative from the family of nonsteroidal anti-inflammatory drugs (NSAIDs).

A 40-year-old woman was referred to the dermatology department due to the sudden onset of multiple pustules on the face. One week earlier she started oral flurbiprofen (8.75 mg daily) for a sore throat. After 3 days of therapy, multiple pruritic, erythematous and edematous lesions appeared abruptly on the face with associated multiple small nonfollicular pustules. At presentation the patient was febrile (temperature, 38.2°C) and presented with bilateral ocular edema and superficial small nonfollicular pustules on an erythematous background over the face, scalp, and oral mucosa (Figure 1). The rest of the body was not involved. The patient denied prior adverse reactions to other drugs. The white blood cell count was 15,000/μL (reference range, 4500–11,000/μL), with an increased neutrophil count (12,000/μL [reference range, 1800–7800/μL]). The erythrocyte sedimentation rate and C-reactive protein level was elevated (erythrocyte sedimentation rate, 53 mm/h [reference range, 0–20 mm/h]; C-reactive protein, 98 mg/dL [reference range, 0–5 mg/dL]). Bacterial and fungal cultures of skin lesions were negative. The results of a viral polymerase chain reaction analysis proved the absence of varicella-zoster virus or herpes simplex virus. Histopathology of a skin biopsy specimen showed subcorneal pustules composed of neutrophils and eosinophils, epidermal spongiosis, some necrotic keratinocytes, vacuolization of the basal layer, papillary edema, and a perivascular neutrophil and lymphocyte infiltrate (Figure 2). A leukocytoclastic infiltrate within and around the walls of blood vessels at the superficial level of the dermis and red cell extravasation in the epidermis was present. She discontinued use of flurbiprofen and was treated with a systemic corticosteroid (methylprednisolone 0.5 mg/kg daily). The pustules rapidly resolved within 7 days after discontinuation of flurbiprofen and were followed by transient scaling and discrete residual hyperpigmentation.

Acute localized exanthematous pustulosis is a less common form of a pustular drug eruption in which lesions are consistent with AGEP but typically are localized to the face, neck, or chest. The definition of ALEP was introduced by Prange et al¹ to describe a woman who was diagnosed with a localized pustular eruption on the face without a generalized distribution as in AGEP. In the past, this localized eruption was described under different names (eg, localized pustular eruption, localized toxin follicular pustuloderma, nongeneralized acute exanthematic pustulosis).^2-5 According to a PubMed search of articles indexed for MEDLINE using the terms localized pustulosis, localized pustular eruption, and localized pustuloderma, only 16 separate cases of ALEP have been documented since the report by Prange et al.¹ The medications most frequently responsible are antibiotics. Three cases developed following administration of amoxicillin^2,5,6; 2 cases of amoxicillin–clavulanic acid^7,8; 1 of penicillin¹; 1 of azithromycin⁹; 1 of levofloxacin¹⁰; and 1 of combination of cephalosporin, sulfamethoxazole-trimethoprim, and vancomycin.¹¹ Other nonantibiotic causative drugs include sulfamethoxazole-trimethoprim,¹² infliximab,¹³ sorafenib,¹⁴ docetaxel,¹⁵ finasteride,¹⁶ ibuprofen,¹⁷ and paracetamol.¹⁸ In reported cases, the lesions are consistent with the characteristics of AGEP both clinically and histopathologically but are localized typically to the face, neck, or chest. In the majority of patients with ALEP, the absence of fever has been observed, but it does not appear distinctive for diagnosis. Our patient represents another case of ALEP with flurbiprofen as the causative drug. The close relationship between the administration of the drug and the development of the pustules, the rapid acute resolution as soon as treatment was interrupted, and the histologic findings all supported the diagnosis of ALEP following administration of flurbiprofen. This NSAID—2-fluoro-α-methyl-(1,1'-biphenyl)-4-acetic acid—is a prostaglandin synthetase inhibitor with anti-inflammatory activity. It is a propionic acid derivative that is similar to ibuprofen, which was once involved in the occurrence of ALEP.¹⁷ In 2009, Rastogi et al¹⁷ reported a case of a 64-year-old woman with an acute outbreak of multiple pustular lesions and underlying erythema affecting the cheeks and chin without fever who had been taking ibuprofen for a toothache. The case is similar to ours and confirms that NSAIDs can induce ALEP. Compared with other NSAIDs, propionic acid derivatives are usually well tolerated and serious adverse reactions rarely have been documented.¹⁹

The physiopathologic mechanisms of ALEP are unknown but likely are similar to AGEP. The demonstration of drug-specific positive patch test responses and in vitro lymphocyte proliferative responses in patients with a history of AGEP strongly suggests that this adverse cutaneous reaction occurs via a drug-specific T cell–mediated process.²⁰

Further study is needed to understand the etiopathogenesis of the localized form of the disease and to facilitate a correct diagnosis of this rare disorder.

To the Editor:

Acute generalized exanthematous pustulosis (AGEP) is an acute skin reaction that is characterized by generalized, nonfollicular, pinhead-sized, sterile pustules on an erythematous and edematous background. The eruption can be accompanied by fever and neutrophilic leukocytosis. Skin symptoms arise quickly (within a few hours), most commonly following drug administration. The medications most frequently responsible are beta-lactam antibiotics, macrolides, calcium channel blockers, and antimalarials. Pustules spontaneously resolve in 15 days and generalized desquamation occurs approximately 2 weeks later. The estimated incidence rate of AGEP is approximately 1 to 5 cases per million per year. Acute localized exanthematous pustulosis (ALEP) is a less common form of AGEP. We report a case of ALEP localized on the face that was caused by flurbiprofen, a propionic acid derivative from the family of nonsteroidal anti-inflammatory drugs (NSAIDs).

A 40-year-old woman was referred to the dermatology department due to the sudden onset of multiple pustules on the face. One week earlier she started oral flurbiprofen (8.75 mg daily) for a sore throat. After 3 days of therapy, multiple pruritic, erythematous and edematous lesions appeared abruptly on the face with associated multiple small nonfollicular pustules. At presentation the patient was febrile (temperature, 38.2°C) and presented with bilateral ocular edema and superficial small nonfollicular pustules on an erythematous background over the face, scalp, and oral mucosa (Figure 1). The rest of the body was not involved. The patient denied prior adverse reactions to other drugs. The white blood cell count was 15,000/μL (reference range, 4500–11,000/μL), with an increased neutrophil count (12,000/μL [reference range, 1800–7800/μL]). The erythrocyte sedimentation rate and C-reactive protein level was elevated (erythrocyte sedimentation rate, 53 mm/h [reference range, 0–20 mm/h]; C-reactive protein, 98 mg/dL [reference range, 0–5 mg/dL]). Bacterial and fungal cultures of skin lesions were negative. The results of a viral polymerase chain reaction analysis proved the absence of varicella-zoster virus or herpes simplex virus. Histopathology of a skin biopsy specimen showed subcorneal pustules composed of neutrophils and eosinophils, epidermal spongiosis, some necrotic keratinocytes, vacuolization of the basal layer, papillary edema, and a perivascular neutrophil and lymphocyte infiltrate (Figure 2). A leukocytoclastic infiltrate within and around the walls of blood vessels at the superficial level of the dermis and red cell extravasation in the epidermis was present. She discontinued use of flurbiprofen and was treated with a systemic corticosteroid (methylprednisolone 0.5 mg/kg daily). The pustules rapidly resolved within 7 days after discontinuation of flurbiprofen and were followed by transient scaling and discrete residual hyperpigmentation.

Acute localized exanthematous pustulosis is a less common form of a pustular drug eruption in which lesions are consistent with AGEP but typically are localized to the face, neck, or chest. The definition of ALEP was introduced by Prange et al¹ to describe a woman who was diagnosed with a localized pustular eruption on the face without a generalized distribution as in AGEP. In the past, this localized eruption was described under different names (eg, localized pustular eruption, localized toxin follicular pustuloderma, nongeneralized acute exanthematic pustulosis).^2-5 According to a PubMed search of articles indexed for MEDLINE using the terms localized pustulosis, localized pustular eruption, and localized pustuloderma, only 16 separate cases of ALEP have been documented since the report by Prange et al.¹ The medications most frequently responsible are antibiotics. Three cases developed following administration of amoxicillin^2,5,6; 2 cases of amoxicillin–clavulanic acid^7,8; 1 of penicillin¹; 1 of azithromycin⁹; 1 of levofloxacin¹⁰; and 1 of combination of cephalosporin, sulfamethoxazole-trimethoprim, and vancomycin.¹¹ Other nonantibiotic causative drugs include sulfamethoxazole-trimethoprim,¹² infliximab,¹³ sorafenib,¹⁴ docetaxel,¹⁵ finasteride,¹⁶ ibuprofen,¹⁷ and paracetamol.¹⁸ In reported cases, the lesions are consistent with the characteristics of AGEP both clinically and histopathologically but are localized typically to the face, neck, or chest. In the majority of patients with ALEP, the absence of fever has been observed, but it does not appear distinctive for diagnosis. Our patient represents another case of ALEP with flurbiprofen as the causative drug. The close relationship between the administration of the drug and the development of the pustules, the rapid acute resolution as soon as treatment was interrupted, and the histologic findings all supported the diagnosis of ALEP following administration of flurbiprofen. This NSAID—2-fluoro-α-methyl-(1,1'-biphenyl)-4-acetic acid—is a prostaglandin synthetase inhibitor with anti-inflammatory activity. It is a propionic acid derivative that is similar to ibuprofen, which was once involved in the occurrence of ALEP.¹⁷ In 2009, Rastogi et al¹⁷ reported a case of a 64-year-old woman with an acute outbreak of multiple pustular lesions and underlying erythema affecting the cheeks and chin without fever who had been taking ibuprofen for a toothache. The case is similar to ours and confirms that NSAIDs can induce ALEP. Compared with other NSAIDs, propionic acid derivatives are usually well tolerated and serious adverse reactions rarely have been documented.¹⁹

The physiopathologic mechanisms of ALEP are unknown but likely are similar to AGEP. The demonstration of drug-specific positive patch test responses and in vitro lymphocyte proliferative responses in patients with a history of AGEP strongly suggests that this adverse cutaneous reaction occurs via a drug-specific T cell–mediated process.²⁰

Further study is needed to understand the etiopathogenesis of the localized form of the disease and to facilitate a correct diagnosis of this rare disorder.

To the Editor:

Acute generalized exanthematous pustulosis (AGEP) is an acute skin reaction that is characterized by generalized, nonfollicular, pinhead-sized, sterile pustules on an erythematous and edematous background. The eruption can be accompanied by fever and neutrophilic leukocytosis. Skin symptoms arise quickly (within a few hours), most commonly following drug administration. The medications most frequently responsible are beta-lactam antibiotics, macrolides, calcium channel blockers, and antimalarials. Pustules spontaneously resolve in 15 days and generalized desquamation occurs approximately 2 weeks later. The estimated incidence rate of AGEP is approximately 1 to 5 cases per million per year. Acute localized exanthematous pustulosis (ALEP) is a less common form of AGEP. We report a case of ALEP localized on the face that was caused by flurbiprofen, a propionic acid derivative from the family of nonsteroidal anti-inflammatory drugs (NSAIDs).

A 40-year-old woman was referred to the dermatology department due to the sudden onset of multiple pustules on the face. One week earlier she started oral flurbiprofen (8.75 mg daily) for a sore throat. After 3 days of therapy, multiple pruritic, erythematous and edematous lesions appeared abruptly on the face with associated multiple small nonfollicular pustules. At presentation the patient was febrile (temperature, 38.2°C) and presented with bilateral ocular edema and superficial small nonfollicular pustules on an erythematous background over the face, scalp, and oral mucosa (Figure 1). The rest of the body was not involved. The patient denied prior adverse reactions to other drugs. The white blood cell count was 15,000/μL (reference range, 4500–11,000/μL), with an increased neutrophil count (12,000/μL [reference range, 1800–7800/μL]). The erythrocyte sedimentation rate and C-reactive protein level was elevated (erythrocyte sedimentation rate, 53 mm/h [reference range, 0–20 mm/h]; C-reactive protein, 98 mg/dL [reference range, 0–5 mg/dL]). Bacterial and fungal cultures of skin lesions were negative. The results of a viral polymerase chain reaction analysis proved the absence of varicella-zoster virus or herpes simplex virus. Histopathology of a skin biopsy specimen showed subcorneal pustules composed of neutrophils and eosinophils, epidermal spongiosis, some necrotic keratinocytes, vacuolization of the basal layer, papillary edema, and a perivascular neutrophil and lymphocyte infiltrate (Figure 2). A leukocytoclastic infiltrate within and around the walls of blood vessels at the superficial level of the dermis and red cell extravasation in the epidermis was present. She discontinued use of flurbiprofen and was treated with a systemic corticosteroid (methylprednisolone 0.5 mg/kg daily). The pustules rapidly resolved within 7 days after discontinuation of flurbiprofen and were followed by transient scaling and discrete residual hyperpigmentation.

Acute localized exanthematous pustulosis is a less common form of a pustular drug eruption in which lesions are consistent with AGEP but typically are localized to the face, neck, or chest. The definition of ALEP was introduced by Prange et al¹ to describe a woman who was diagnosed with a localized pustular eruption on the face without a generalized distribution as in AGEP. In the past, this localized eruption was described under different names (eg, localized pustular eruption, localized toxin follicular pustuloderma, nongeneralized acute exanthematic pustulosis).^2-5 According to a PubMed search of articles indexed for MEDLINE using the terms localized pustulosis, localized pustular eruption, and localized pustuloderma, only 16 separate cases of ALEP have been documented since the report by Prange et al.¹ The medications most frequently responsible are antibiotics. Three cases developed following administration of amoxicillin^2,5,6; 2 cases of amoxicillin–clavulanic acid^7,8; 1 of penicillin¹; 1 of azithromycin⁹; 1 of levofloxacin¹⁰; and 1 of combination of cephalosporin, sulfamethoxazole-trimethoprim, and vancomycin.¹¹ Other nonantibiotic causative drugs include sulfamethoxazole-trimethoprim,¹² infliximab,¹³ sorafenib,¹⁴ docetaxel,¹⁵ finasteride,¹⁶ ibuprofen,¹⁷ and paracetamol.¹⁸ In reported cases, the lesions are consistent with the characteristics of AGEP both clinically and histopathologically but are localized typically to the face, neck, or chest. In the majority of patients with ALEP, the absence of fever has been observed, but it does not appear distinctive for diagnosis. Our patient represents another case of ALEP with flurbiprofen as the causative drug. The close relationship between the administration of the drug and the development of the pustules, the rapid acute resolution as soon as treatment was interrupted, and the histologic findings all supported the diagnosis of ALEP following administration of flurbiprofen. This NSAID—2-fluoro-α-methyl-(1,1'-biphenyl)-4-acetic acid—is a prostaglandin synthetase inhibitor with anti-inflammatory activity. It is a propionic acid derivative that is similar to ibuprofen, which was once involved in the occurrence of ALEP.¹⁷ In 2009, Rastogi et al¹⁷ reported a case of a 64-year-old woman with an acute outbreak of multiple pustular lesions and underlying erythema affecting the cheeks and chin without fever who had been taking ibuprofen for a toothache. The case is similar to ours and confirms that NSAIDs can induce ALEP. Compared with other NSAIDs, propionic acid derivatives are usually well tolerated and serious adverse reactions rarely have been documented.¹⁹

The physiopathologic mechanisms of ALEP are unknown but likely are similar to AGEP. The demonstration of drug-specific positive patch test responses and in vitro lymphocyte proliferative responses in patients with a history of AGEP strongly suggests that this adverse cutaneous reaction occurs via a drug-specific T cell–mediated process.²⁰

Further study is needed to understand the etiopathogenesis of the localized form of the disease and to facilitate a correct diagnosis of this rare disorder.

To the Editor:

Prior studies have assessed the quality of text-based dermatology information on the Internet using traditional search engine queries.¹ However, little is understood about the sources, accuracy, and quality of online dermatology images derived from direct image searches. Previous work has shown that direct search engine image queries were largely accurate for 3 pediatric dermatology diagnosis searches: atopic dermatitis, lichen striatus, and subcutaneous fat necrosis.² We assessed images obtained for common dermatologic conditions from a Google image search (GIS) compared to a traditional text-based Google web search (GWS).

Image results for 32 unique dermatologic search terms were analyzed (Table 1). These search terms were selected using the results of a prior study that identified the most common dermatologic diagnoses that led users to the 2 most popular dermatology-specific websites worldwide: the American Academy of Dermatology (www.aad.org) and DermNet New Zealand (www.dermnetnz.org).³ The Alexa directory (www.alexa.com), a large publicly available Internet analytics resource, was used to determine the most common dermatology search terms that led a user to either www.dermnetnz.org or www.aad.org. In addition, searches for the 3 most common types of skin cancer—melanoma, squamous cell carcinoma, and basal cell carcinoma—were included. Each term was entered into a GIS and a GWS. The first 10 results, which represent 92% of the websites ultimately visited by users,⁴ were analyzed. The source, diagnostic accuracy, and Fitzpatrick skin type of the images was determined. Website sources were organized into 11 categories. All data collection occurred within a 1-week period in August 2015.

A total of 320 images were analyzed. In the GIS, private websites (36%), dermatology association websites (28%), and general health information websites (10%) were the 3 most common sources. In the GWS, health information websites (35%), private websites (21%), and dermatology association websites (20%) accounted for the most common sources (Table 2). The majority of images were of Fitzpatrick skin types I and II (89%) and nearly all images were diagnostically accurate (98%). There was no statistically significant difference in accuracy of diagnosis between physician-associated websites (100% accuracy) versus nonphysician-associated sites (98% accuracy, P=.25).

Our results showed high diagnostic accuracy among the top GIS results for common dermatology search terms. Diagnostic accuracy did not vary between websites that were physician associated versus those that were not. Our results are comparable to the reported accuracy of online dermatologic health information.¹ In GIS results, the majority of images were provided by private websites, whereas the top websites in GWS results were health information websites.

Only 1% of images were of Fitzpatrick skin types VI and VII. Presentation of skin diseases is remarkably different based on the patient’s skin type.⁵ The shortage of readily accessible images of skin of color is in line with the lack of familiarity physicians and trainees have with dermatologic conditions in ethnic skin.⁶

Based on the results from this analysis, providers and patients searching for dermatologic conditions via a direct GIS should be cognizant of several considerations. Although our results showed that GIS was accurate, the searcher should note that image-based searches are not accompanied by relevant text that can help confirm relevancy and accuracy. Image searches depend on textual tags added by the source website. Websites that represent dermatological associations and academic centers can add an additional layer of confidence for users. Patients and clinicians also should be aware that the consideration of a patient’s Fitzpatrick skin type is critical when assessing the relevancy of a GIS result. In conclusion, search results via GIS queries are accurate for the dermatological diagnoses tested but may be lacking in skin of color variations, suggesting a potential unmet need based on our growing ethnic skin population.

To the Editor:

Prior studies have assessed the quality of text-based dermatology information on the Internet using traditional search engine queries.¹ However, little is understood about the sources, accuracy, and quality of online dermatology images derived from direct image searches. Previous work has shown that direct search engine image queries were largely accurate for 3 pediatric dermatology diagnosis searches: atopic dermatitis, lichen striatus, and subcutaneous fat necrosis.² We assessed images obtained for common dermatologic conditions from a Google image search (GIS) compared to a traditional text-based Google web search (GWS).

Image results for 32 unique dermatologic search terms were analyzed (Table 1). These search terms were selected using the results of a prior study that identified the most common dermatologic diagnoses that led users to the 2 most popular dermatology-specific websites worldwide: the American Academy of Dermatology (www.aad.org) and DermNet New Zealand (www.dermnetnz.org).³ The Alexa directory (www.alexa.com), a large publicly available Internet analytics resource, was used to determine the most common dermatology search terms that led a user to either www.dermnetnz.org or www.aad.org. In addition, searches for the 3 most common types of skin cancer—melanoma, squamous cell carcinoma, and basal cell carcinoma—were included. Each term was entered into a GIS and a GWS. The first 10 results, which represent 92% of the websites ultimately visited by users,⁴ were analyzed. The source, diagnostic accuracy, and Fitzpatrick skin type of the images was determined. Website sources were organized into 11 categories. All data collection occurred within a 1-week period in August 2015.

A total of 320 images were analyzed. In the GIS, private websites (36%), dermatology association websites (28%), and general health information websites (10%) were the 3 most common sources. In the GWS, health information websites (35%), private websites (21%), and dermatology association websites (20%) accounted for the most common sources (Table 2). The majority of images were of Fitzpatrick skin types I and II (89%) and nearly all images were diagnostically accurate (98%). There was no statistically significant difference in accuracy of diagnosis between physician-associated websites (100% accuracy) versus nonphysician-associated sites (98% accuracy, P=.25).

Our results showed high diagnostic accuracy among the top GIS results for common dermatology search terms. Diagnostic accuracy did not vary between websites that were physician associated versus those that were not. Our results are comparable to the reported accuracy of online dermatologic health information.¹ In GIS results, the majority of images were provided by private websites, whereas the top websites in GWS results were health information websites.

Only 1% of images were of Fitzpatrick skin types VI and VII. Presentation of skin diseases is remarkably different based on the patient’s skin type.⁵ The shortage of readily accessible images of skin of color is in line with the lack of familiarity physicians and trainees have with dermatologic conditions in ethnic skin.⁶

Based on the results from this analysis, providers and patients searching for dermatologic conditions via a direct GIS should be cognizant of several considerations. Although our results showed that GIS was accurate, the searcher should note that image-based searches are not accompanied by relevant text that can help confirm relevancy and accuracy. Image searches depend on textual tags added by the source website. Websites that represent dermatological associations and academic centers can add an additional layer of confidence for users. Patients and clinicians also should be aware that the consideration of a patient’s Fitzpatrick skin type is critical when assessing the relevancy of a GIS result. In conclusion, search results via GIS queries are accurate for the dermatological diagnoses tested but may be lacking in skin of color variations, suggesting a potential unmet need based on our growing ethnic skin population.

To the Editor:

Prior studies have assessed the quality of text-based dermatology information on the Internet using traditional search engine queries.¹ However, little is understood about the sources, accuracy, and quality of online dermatology images derived from direct image searches. Previous work has shown that direct search engine image queries were largely accurate for 3 pediatric dermatology diagnosis searches: atopic dermatitis, lichen striatus, and subcutaneous fat necrosis.² We assessed images obtained for common dermatologic conditions from a Google image search (GIS) compared to a traditional text-based Google web search (GWS).

Image results for 32 unique dermatologic search terms were analyzed (Table 1). These search terms were selected using the results of a prior study that identified the most common dermatologic diagnoses that led users to the 2 most popular dermatology-specific websites worldwide: the American Academy of Dermatology (www.aad.org) and DermNet New Zealand (www.dermnetnz.org).³ The Alexa directory (www.alexa.com), a large publicly available Internet analytics resource, was used to determine the most common dermatology search terms that led a user to either www.dermnetnz.org or www.aad.org. In addition, searches for the 3 most common types of skin cancer—melanoma, squamous cell carcinoma, and basal cell carcinoma—were included. Each term was entered into a GIS and a GWS. The first 10 results, which represent 92% of the websites ultimately visited by users,⁴ were analyzed. The source, diagnostic accuracy, and Fitzpatrick skin type of the images was determined. Website sources were organized into 11 categories. All data collection occurred within a 1-week period in August 2015.

A total of 320 images were analyzed. In the GIS, private websites (36%), dermatology association websites (28%), and general health information websites (10%) were the 3 most common sources. In the GWS, health information websites (35%), private websites (21%), and dermatology association websites (20%) accounted for the most common sources (Table 2). The majority of images were of Fitzpatrick skin types I and II (89%) and nearly all images were diagnostically accurate (98%). There was no statistically significant difference in accuracy of diagnosis between physician-associated websites (100% accuracy) versus nonphysician-associated sites (98% accuracy, P=.25).

Our results showed high diagnostic accuracy among the top GIS results for common dermatology search terms. Diagnostic accuracy did not vary between websites that were physician associated versus those that were not. Our results are comparable to the reported accuracy of online dermatologic health information.¹ In GIS results, the majority of images were provided by private websites, whereas the top websites in GWS results were health information websites.

Only 1% of images were of Fitzpatrick skin types VI and VII. Presentation of skin diseases is remarkably different based on the patient’s skin type.⁵ The shortage of readily accessible images of skin of color is in line with the lack of familiarity physicians and trainees have with dermatologic conditions in ethnic skin.⁶

Based on the results from this analysis, providers and patients searching for dermatologic conditions via a direct GIS should be cognizant of several considerations. Although our results showed that GIS was accurate, the searcher should note that image-based searches are not accompanied by relevant text that can help confirm relevancy and accuracy. Image searches depend on textual tags added by the source website. Websites that represent dermatological associations and academic centers can add an additional layer of confidence for users. Patients and clinicians also should be aware that the consideration of a patient’s Fitzpatrick skin type is critical when assessing the relevancy of a GIS result. In conclusion, search results via GIS queries are accurate for the dermatological diagnoses tested but may be lacking in skin of color variations, suggesting a potential unmet need based on our growing ethnic skin population.

To improve patient care and outcomes, leading dermatologists offered their recommendations on OTC rosacea treatments. Consideration must be given to:

• Eucerin Redness Relief
  Beiersdorf Inc
  Recommended by Gary Goldenberg, MD, New York, New York
   
• Rosaliac CC Cream
  La Roche-Posay Laboratoire Dermatologique
  “This product provides hydration and an even tint to correct and reduce the erythema of rosacea. It is made with both titanium dioxide and organic UV filters to give broad-spectrum coverage with SPF 30.”—Cherise Mizrahi-Levi, DO, New York, New York
   
• Vanicream
  Pharmaceutical Specialties, Inc.
  “I like Vanicream products since they are mild and hypoallergenic.”—Gary Goldenberg, MD, New York, New York
   

Cutis invites readers to send us their recommendations. Cleansing devices, skin-lightening agents, and self-tanners will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on OTC rosacea treatments. Consideration must be given to:

• Eucerin Redness Relief
  Beiersdorf Inc
  Recommended by Gary Goldenberg, MD, New York, New York
   
• Rosaliac CC Cream
  La Roche-Posay Laboratoire Dermatologique
  “This product provides hydration and an even tint to correct and reduce the erythema of rosacea. It is made with both titanium dioxide and organic UV filters to give broad-spectrum coverage with SPF 30.”—Cherise Mizrahi-Levi, DO, New York, New York
   
• Vanicream
  Pharmaceutical Specialties, Inc.
  “I like Vanicream products since they are mild and hypoallergenic.”—Gary Goldenberg, MD, New York, New York
   

Cutis invites readers to send us their recommendations. Cleansing devices, skin-lightening agents, and self-tanners will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on OTC rosacea treatments. Consideration must be given to:

• Eucerin Redness Relief
  Beiersdorf Inc
  Recommended by Gary Goldenberg, MD, New York, New York
   
• Rosaliac CC Cream
  La Roche-Posay Laboratoire Dermatologique
  “This product provides hydration and an even tint to correct and reduce the erythema of rosacea. It is made with both titanium dioxide and organic UV filters to give broad-spectrum coverage with SPF 30.”—Cherise Mizrahi-Levi, DO, New York, New York
   
• Vanicream
  Pharmaceutical Specialties, Inc.
  “I like Vanicream products since they are mild and hypoallergenic.”—Gary Goldenberg, MD, New York, New York
   

Cutis invites readers to send us their recommendations. Cleansing devices, skin-lightening agents, and self-tanners will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

The Diagnosis: Dental Sinus Secondary to Osteonecrosis of the Jaw

Cone beam computed tomography revealed an area of lucency measuring 40×20 mm in the body of the right mandible (Figure). The patient subsequently underwent curettage of the wound with sequestrectomy of the involved area.

Osteonecrosis of the jaw is a form of avascular necrosis. It is an uncommon but potentially serious side effect of bisphosphonate use.¹ Bisphosphonates commonly are used as first-line therapy for osteoporosis, with proven efficacy to reduce fracture risk by exerting an antiresorptive effect on bones.² Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons as the presence of exposed necrotic bone in the maxillofacial region that has persisted for more than 8 weeks, with current or prior treatment with a bisphosphonate and absence of prior radiation therapy to the jaw.3 Bisphosphonate-related osteonecrosis of the jaw can be associated with infections, pathologic fractures, extraoral fistulae, or osteolysis extending to the inferior border.

Our patient had a dental sinus that resulted from the underlying BRONJ. The jawbones, unlike the long bones, are in a special environment in that both acute and chronic infections occur often within the bone, and surgical procedures as well as masticatory trauma expose the bone to a bacteria-laden environment.⁴ Infection around the root apex of a tooth results in a dental abscess and a sinus tract can develop from the abscess, draining either intraorally or extraorally.⁵ Facial sinus tracts can be either odontogenic or nonodontogenic, and sometimes the lesions of dental origin may be confused with dermatological lesions.

Bisphosphonates inhibit osteoclasts, which are responsible for bone resorption. Antiangiogenetic effects also have been reported in bisphosphonates, resulting in devitalized bone.⁶ The potent and prolonged inhibition of bone remodeling likely plays an important role in BRONJ. The more frequently occurring microdamage inflicted on the lower jawbone with mastication also may represent a contributory factor.⁷

Bisphosphonate-related osteonecrosis of the jaw more often is associated with the use of high-dose intravenous (IV) bisphosphonate in cancer-related hypercalcemia and less so with oral bisphosphonates, which are generally used to treat osteoporosis.³ In a Swedish study conducted from 2003 to 2010, 55 cases of BRONJ were documented in a population of 1.2 million individuals. The prevalence of BRONJ in patients on oral bisphosphonates and IV bisphosphonates was estimated to be 0.024% and 2.8%, respectively.⁸

Bisphosphonates are widely used worldwide as the main treatment of osteoporosis. The association between osteonecrosis of the jaw and oral bisphosphonates is contentious among the osteoporosis population, as most studies focus on IV bisphosphonate use in cancer patients.⁹ Bisphosphonate-related osteonecrosis of the jaw adversely affects the patient's quality of life, producing notable morbidity in afflicted patients. Thus, a complete dental assessment and treatment is recommended before the initiation of bisphosphonate treatment. The risk for developing BRONJ associated with oral bisphosphonates increases when the duration of therapy exceeds 3 years.³ It has been reported that antifracture efficacy would persist for 1 to 2 years following discontinuation of alendronate or risedronate that had been taken for 3 to 5 years, but patients with low bone mineral density at the femoral neck (T-score below -2.5) after 3 to 5 years of treatment of bisphosphonates are at the highest risk for vertebral fractures and therefore appear to benefit most from continuation of therapy.¹⁰ For dental procedures, the American Association of Oral and Maxillofacial Surgeons suggests that if systemic conditions persist, the clinician might consider discontinuation of oral bisphosphonates for a 3-month period before and after elective invasive dental surgery to lower the risk for BRONJ.³ When possible, invasive dentoalveolar procedures such as extractions should be avoided; conservative endodontic treatment is preferable.

Bisphosphonate-related osteonecrosis of the jaw is a devastating condition that is difficult to treat and manage, thus the focus should be on prevention through dental clearance prior to starting bisphosphonates. It also is crucial to have a high index of suspicion for BRONJ in patients presenting with orofacial lesions so that they can be treated expediently.

The Diagnosis: Dental Sinus Secondary to Osteonecrosis of the Jaw

Cone beam computed tomography revealed an area of lucency measuring 40×20 mm in the body of the right mandible (Figure). The patient subsequently underwent curettage of the wound with sequestrectomy of the involved area.

Osteonecrosis of the jaw is a form of avascular necrosis. It is an uncommon but potentially serious side effect of bisphosphonate use.¹ Bisphosphonates commonly are used as first-line therapy for osteoporosis, with proven efficacy to reduce fracture risk by exerting an antiresorptive effect on bones.² Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons as the presence of exposed necrotic bone in the maxillofacial region that has persisted for more than 8 weeks, with current or prior treatment with a bisphosphonate and absence of prior radiation therapy to the jaw.3 Bisphosphonate-related osteonecrosis of the jaw can be associated with infections, pathologic fractures, extraoral fistulae, or osteolysis extending to the inferior border.

Our patient had a dental sinus that resulted from the underlying BRONJ. The jawbones, unlike the long bones, are in a special environment in that both acute and chronic infections occur often within the bone, and surgical procedures as well as masticatory trauma expose the bone to a bacteria-laden environment.⁴ Infection around the root apex of a tooth results in a dental abscess and a sinus tract can develop from the abscess, draining either intraorally or extraorally.⁵ Facial sinus tracts can be either odontogenic or nonodontogenic, and sometimes the lesions of dental origin may be confused with dermatological lesions.

Bisphosphonates inhibit osteoclasts, which are responsible for bone resorption. Antiangiogenetic effects also have been reported in bisphosphonates, resulting in devitalized bone.⁶ The potent and prolonged inhibition of bone remodeling likely plays an important role in BRONJ. The more frequently occurring microdamage inflicted on the lower jawbone with mastication also may represent a contributory factor.⁷

Bisphosphonate-related osteonecrosis of the jaw more often is associated with the use of high-dose intravenous (IV) bisphosphonate in cancer-related hypercalcemia and less so with oral bisphosphonates, which are generally used to treat osteoporosis.³ In a Swedish study conducted from 2003 to 2010, 55 cases of BRONJ were documented in a population of 1.2 million individuals. The prevalence of BRONJ in patients on oral bisphosphonates and IV bisphosphonates was estimated to be 0.024% and 2.8%, respectively.⁸

Bisphosphonates are widely used worldwide as the main treatment of osteoporosis. The association between osteonecrosis of the jaw and oral bisphosphonates is contentious among the osteoporosis population, as most studies focus on IV bisphosphonate use in cancer patients.⁹ Bisphosphonate-related osteonecrosis of the jaw adversely affects the patient's quality of life, producing notable morbidity in afflicted patients. Thus, a complete dental assessment and treatment is recommended before the initiation of bisphosphonate treatment. The risk for developing BRONJ associated with oral bisphosphonates increases when the duration of therapy exceeds 3 years.³ It has been reported that antifracture efficacy would persist for 1 to 2 years following discontinuation of alendronate or risedronate that had been taken for 3 to 5 years, but patients with low bone mineral density at the femoral neck (T-score below -2.5) after 3 to 5 years of treatment of bisphosphonates are at the highest risk for vertebral fractures and therefore appear to benefit most from continuation of therapy.¹⁰ For dental procedures, the American Association of Oral and Maxillofacial Surgeons suggests that if systemic conditions persist, the clinician might consider discontinuation of oral bisphosphonates for a 3-month period before and after elective invasive dental surgery to lower the risk for BRONJ.³ When possible, invasive dentoalveolar procedures such as extractions should be avoided; conservative endodontic treatment is preferable.

Bisphosphonate-related osteonecrosis of the jaw is a devastating condition that is difficult to treat and manage, thus the focus should be on prevention through dental clearance prior to starting bisphosphonates. It also is crucial to have a high index of suspicion for BRONJ in patients presenting with orofacial lesions so that they can be treated expediently.

The Diagnosis: Dental Sinus Secondary to Osteonecrosis of the Jaw

Cone beam computed tomography revealed an area of lucency measuring 40×20 mm in the body of the right mandible (Figure). The patient subsequently underwent curettage of the wound with sequestrectomy of the involved area.

Osteonecrosis of the jaw is a form of avascular necrosis. It is an uncommon but potentially serious side effect of bisphosphonate use.¹ Bisphosphonates commonly are used as first-line therapy for osteoporosis, with proven efficacy to reduce fracture risk by exerting an antiresorptive effect on bones.² Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons as the presence of exposed necrotic bone in the maxillofacial region that has persisted for more than 8 weeks, with current or prior treatment with a bisphosphonate and absence of prior radiation therapy to the jaw.3 Bisphosphonate-related osteonecrosis of the jaw can be associated with infections, pathologic fractures, extraoral fistulae, or osteolysis extending to the inferior border.

Our patient had a dental sinus that resulted from the underlying BRONJ. The jawbones, unlike the long bones, are in a special environment in that both acute and chronic infections occur often within the bone, and surgical procedures as well as masticatory trauma expose the bone to a bacteria-laden environment.⁴ Infection around the root apex of a tooth results in a dental abscess and a sinus tract can develop from the abscess, draining either intraorally or extraorally.⁵ Facial sinus tracts can be either odontogenic or nonodontogenic, and sometimes the lesions of dental origin may be confused with dermatological lesions.

Bisphosphonates inhibit osteoclasts, which are responsible for bone resorption. Antiangiogenetic effects also have been reported in bisphosphonates, resulting in devitalized bone.⁶ The potent and prolonged inhibition of bone remodeling likely plays an important role in BRONJ. The more frequently occurring microdamage inflicted on the lower jawbone with mastication also may represent a contributory factor.⁷

Bisphosphonate-related osteonecrosis of the jaw more often is associated with the use of high-dose intravenous (IV) bisphosphonate in cancer-related hypercalcemia and less so with oral bisphosphonates, which are generally used to treat osteoporosis.³ In a Swedish study conducted from 2003 to 2010, 55 cases of BRONJ were documented in a population of 1.2 million individuals. The prevalence of BRONJ in patients on oral bisphosphonates and IV bisphosphonates was estimated to be 0.024% and 2.8%, respectively.⁸

Bisphosphonates are widely used worldwide as the main treatment of osteoporosis. The association between osteonecrosis of the jaw and oral bisphosphonates is contentious among the osteoporosis population, as most studies focus on IV bisphosphonate use in cancer patients.⁹ Bisphosphonate-related osteonecrosis of the jaw adversely affects the patient's quality of life, producing notable morbidity in afflicted patients. Thus, a complete dental assessment and treatment is recommended before the initiation of bisphosphonate treatment. The risk for developing BRONJ associated with oral bisphosphonates increases when the duration of therapy exceeds 3 years.³ It has been reported that antifracture efficacy would persist for 1 to 2 years following discontinuation of alendronate or risedronate that had been taken for 3 to 5 years, but patients with low bone mineral density at the femoral neck (T-score below -2.5) after 3 to 5 years of treatment of bisphosphonates are at the highest risk for vertebral fractures and therefore appear to benefit most from continuation of therapy.¹⁰ For dental procedures, the American Association of Oral and Maxillofacial Surgeons suggests that if systemic conditions persist, the clinician might consider discontinuation of oral bisphosphonates for a 3-month period before and after elective invasive dental surgery to lower the risk for BRONJ.³ When possible, invasive dentoalveolar procedures such as extractions should be avoided; conservative endodontic treatment is preferable.

Bisphosphonate-related osteonecrosis of the jaw is a devastating condition that is difficult to treat and manage, thus the focus should be on prevention through dental clearance prior to starting bisphosphonates. It also is crucial to have a high index of suspicion for BRONJ in patients presenting with orofacial lesions so that they can be treated expediently.

To the Editor:

A 42-year-old woman who had a tattoo on the right wrist surgically removed 2 days prior developed severe erythema and swelling at the incision site (Figure 1). Exposure at the incision site was limited to bacitracin, poliglecaprone 25 suture, and plain cotton gauze. Patch testing of bacitracin was performed, which was ++ (moderately positive reaction) at the 96-hour reading, indicating that part of the reaction was due to the topical antibiotic. Testing of the suture was performed by tying the suture to the skin of the forearm and removing it at 48 hours. There was a ++ reaction to the suture prior to removal at 48 hours, which increased to +++ (severely positive reaction) after suture removal at 96 hours (Figure 2). Therefore, it appears that allergy to the suture also was partially responsible for the postsurgical reaction.

Poliglecaprone 25 suture is a monofilament synthetic absorbable material that is a copolymer of glycolide and ε-caprolactone. One case report of oral contact allergy to this suture material resulted in failure of an oral graft; however, no testing was performed to verify the contact allergy.¹ Caprolactam ([CH₂]₅C[O]NH) is a related chemical that can be synthesized by treating caprolactone ([CH₂]₅CO₂) with ammonia at elevated temperatures.² Contact allergy has been reported to polyamide 6 suture, which is obtained by polymerizing ε-caprolactam. This report stated that contact allergy to ε-caprolactam also has been reported occupationally during manufacture and from its use in fishing nets, socks, gloves, and stockings.³

The package insert for the poliglecaprone 25 suture states that the material is “nonantigenic, nonpyrogenic and elicits only a slight tissue reaction during absorption.”⁴ We present a case of contact allergy to poliglecaprone 25 suture that was confirmed by allergy testing.

To the Editor:

A 42-year-old woman who had a tattoo on the right wrist surgically removed 2 days prior developed severe erythema and swelling at the incision site (Figure 1). Exposure at the incision site was limited to bacitracin, poliglecaprone 25 suture, and plain cotton gauze. Patch testing of bacitracin was performed, which was ++ (moderately positive reaction) at the 96-hour reading, indicating that part of the reaction was due to the topical antibiotic. Testing of the suture was performed by tying the suture to the skin of the forearm and removing it at 48 hours. There was a ++ reaction to the suture prior to removal at 48 hours, which increased to +++ (severely positive reaction) after suture removal at 96 hours (Figure 2). Therefore, it appears that allergy to the suture also was partially responsible for the postsurgical reaction.

Poliglecaprone 25 suture is a monofilament synthetic absorbable material that is a copolymer of glycolide and ε-caprolactone. One case report of oral contact allergy to this suture material resulted in failure of an oral graft; however, no testing was performed to verify the contact allergy.¹ Caprolactam ([CH₂]₅C[O]NH) is a related chemical that can be synthesized by treating caprolactone ([CH₂]₅CO₂) with ammonia at elevated temperatures.² Contact allergy has been reported to polyamide 6 suture, which is obtained by polymerizing ε-caprolactam. This report stated that contact allergy to ε-caprolactam also has been reported occupationally during manufacture and from its use in fishing nets, socks, gloves, and stockings.³

The package insert for the poliglecaprone 25 suture states that the material is “nonantigenic, nonpyrogenic and elicits only a slight tissue reaction during absorption.”⁴ We present a case of contact allergy to poliglecaprone 25 suture that was confirmed by allergy testing.

To the Editor:

A 42-year-old woman who had a tattoo on the right wrist surgically removed 2 days prior developed severe erythema and swelling at the incision site (Figure 1). Exposure at the incision site was limited to bacitracin, poliglecaprone 25 suture, and plain cotton gauze. Patch testing of bacitracin was performed, which was ++ (moderately positive reaction) at the 96-hour reading, indicating that part of the reaction was due to the topical antibiotic. Testing of the suture was performed by tying the suture to the skin of the forearm and removing it at 48 hours. There was a ++ reaction to the suture prior to removal at 48 hours, which increased to +++ (severely positive reaction) after suture removal at 96 hours (Figure 2). Therefore, it appears that allergy to the suture also was partially responsible for the postsurgical reaction.

Poliglecaprone 25 suture is a monofilament synthetic absorbable material that is a copolymer of glycolide and ε-caprolactone. One case report of oral contact allergy to this suture material resulted in failure of an oral graft; however, no testing was performed to verify the contact allergy.¹ Caprolactam ([CH₂]₅C[O]NH) is a related chemical that can be synthesized by treating caprolactone ([CH₂]₅CO₂) with ammonia at elevated temperatures.² Contact allergy has been reported to polyamide 6 suture, which is obtained by polymerizing ε-caprolactam. This report stated that contact allergy to ε-caprolactam also has been reported occupationally during manufacture and from its use in fishing nets, socks, gloves, and stockings.³

The package insert for the poliglecaprone 25 suture states that the material is “nonantigenic, nonpyrogenic and elicits only a slight tissue reaction during absorption.”⁴ We present a case of contact allergy to poliglecaprone 25 suture that was confirmed by allergy testing.

Sneddon syndrome (SS) was first described in 1965 in patients with persistent livedo racemosa and neurological events.¹ Because the other manifestations of SS are nonspecific (eg, hypertension, cardiac valvulopathy, arterial and venous occlusion), the diagnosis often is delayed. Many patients who experience prodromal neurologic symptoms such as headaches, depression, anxiety, dizziness, and neuropathy often present to a physician prior to developing ischemic brain manifestations² but seldom receive the correct diagnosis. Onset of cerebral occlusive events typically occurs in patients younger than 45 years and may present as a transient ischemic attack, stroke, or intracranial hemorrhage.³ The disease is more prevalent in females than males (2:1 ratio). The exact pathogenesis of SS is still unknown, and although it has been thought of as a separate entity from systemic lupus erythematosus and other antiphospholipid disorders, it has been postulated that an immunological dysfunction damages vessel walls leading to thrombosis.

Cutaneous findings associated with SS involve small- to medium-sized dermal-subdermal arteries. Histopathology in some patients demonstrates proliferation of the endothelium and fibrin deposits with subsequent obliteration of involved arteries.⁴ In many patients including our patient, histopathologic examination of involved skin fails to show specific abnormalities.¹ Zelger et al⁵ reported the sequence of histopathologic skin events in a series of antiphospholipid-negative SS patients. The authors reported that only small arteries at the dermis-subcutis junction were involved and a progression of endothelial dysfunction was observed. The authors believed there were several nonspecific stages prior to fibrin occlusion of involved arteries.⁵ Stage I involved loosening of endothelial cells with nonspecific perivascular lymphocytic infiltration with perivascular inflammation and lymphocytic infiltration representing the prime mover of the disease.^5,6 This stage is thought to be short lived, thus the reason why it has gone undetected for many years in SS patients. Stages II to IV progress through fibrin deposition and occlusion.⁵ Histological features of stages I to II have not been reported because of late diagnosis of SS. Stage I patients typically present with an average duration of symptoms of 6 months with few neurologic symptoms, the most common being paresthesia of the legs.⁵

Case Report

A 37-year-old woman with epigastric tenderness on the left side and splenomegaly seen on computed tomography was referred by a hematologist for evaluation of a reticular rash on the left side of the flank of 9 months’ duration with a presumed diagnosis of focal melanoderma. Her medical history was remarkable for a congenital ventricular septal defect and coarctation of the aorta, as well as endometriosis, myalgia, and joint stiffness that had all developed over the last year. Her medical history also was remarkable for nephrolithiasis, irritable bowel syndrome, and chronic sinusitis, as well as psychiatric depression and anxiety disorders. She recently had been diagnosed with moderate hypertension and had experienced difficulty getting pregnant for the last several years with 3 consecutive miscarriages in the first trimester. Neurologic symptoms included neuropathy involving the feet, intermittent paresthesia of the legs, and a history of chronic migraine headaches for several months.

Dermatologic examination revealed a slightly overweight woman with a 25×30-cm dusky, erythematous, irregular, netlike pattern on the left side of the upper and lower trunk (Figure 1). Extensive livedo racemosa was not altered by changes in temperature and had been unchanged for more than 9 months. There were no signs of pruritus or ulcerations, and areas of livedo racemosa were slightly tender to palpation.

We performed 2 sets of three 4-mm biopsies. The first set targeted areas within the violaceous pattern, while the second set targeted areas of normal tissue between the mottled areas. All 6 specimens demonstrated superficial perivascular lymphocytic infiltrate with no evidence of vasculitis or connective tissue disease. The vessels showed no microthrombi or surrounding fibrosis. No eosinophils were identified within the epidermis. There was no evidence of increased dermal mucin. Both the superficial and deep vascular plexuses were unremarkable and showed no evidence of damage to the walls (Figure 2).

To rule out other possible causes of livedo racemosa, complete blood cell count, comprehensive metabolic panel, coagulation profile, lipase test, urinalysis, serologic testing, and immunologic workup were performed. Lipase was within reference range. The complete blood cell count revealed mild anemia, while the rest of the values were within reference range. An immunologic workup included Sjögren syndrome antigen A, Sjögren syndrome antigen B, anticardiolipin antibodies, and antinuclear antibody, which were all negative. Family history was remarkable for first-degree relatives with systemic lupus erythematosus and Crohn disease.

Computed tomography revealed enlargement of the spleen, as well as periaortic, portacaval, and porta hepatis lymphadenopathy. Based on the laboratory findings and clinical presentation as well as the patient’s medical history, the diagnosis of exclusion was idiopathic livedo racemosa with unknown progression to full-blown SS. The patient did not meet the current diagnostic criteria for SS, and her immunologic studies failed to confirm any present antibodies, but involvement of the reticuloendothelial system pointed to production of antibodies that were not yet detectable on laboratory testing.

Comment

More than 50 years after the first case of SS was diagnosed, better laboratory workup is available and more information is known about the pathophysiology. Sneddon syndrome is a rare disorder, affecting only approximately 4 patients per million each year worldwide. Seronegative antiphospholipid antibody syndrome (SNAPS) describes patients with clinical presentations of antiphospholipid syndrome (APS) without detectable serological markers.⁷ Antiphospholipid-negative SS, which was seen in our patient, would be categorized under SNAPS. A PubMed search of articles indexed for MEDLINE using the terms livedo racemosa, Sneddon syndrome, and SNAPS and splenomegaly revealed there currently are no known cases of SNAPS that have been reported with splenomegaly and lymphadenopathy. Our patient presented with the following clinical features of SS: livedo racemosa, history of miscarriage, psychiatric disturbances, and hypertension. Surprisingly, biopsies from affected skin did not show any fibrin deposition or microthrombi but did reveal perivascular lymphocytic infiltrations. Magnetic resonance imaging did not show any pathological lesions or vascular changes.

Sneddon syndrome and APS share a common pathway to occlusive arteriolopathy for which 4 stages have been described by Zelger et al.⁵ Stage I involves a nonspecific Langerhans cell infiltrate with polymorphonuclear leukocytes. The tunica media and elastic lamina usually are unaltered at this early stage, while the surrounding connective tissue may appear edematous.⁵ This early stage of histopathology has not been evaluated in SS patients, primarily because of delay of diagnosis. Late stages III and IV will show fibrin deposition and shrinkage of affected vessels.⁷

A PubMed search using the terms Sneddon syndrome, lymphadenopathy and livedo racemosa, and Sneddon syndrome and lymphadenopathy revealed that splenomegaly and lymphadenopathy have not been reported in patients with SS. In patients with antiphospholipid-negative SS, one can assume that antibodies to other phospholipids not tested must exist because of striking similarities between APS and antiphospholipid-negative SS.⁸ Although our patient did not test positive for any of these antibodies, she did present with lymphadenopathy and splenic enlargement, leading us to believe that involvement of the reticuloendothelial system may be a feature of SS that has not been previously reported. Further studies are required to name specific antigens responsible for clinical manifestations in SS.

Currently, no single diagnostic test for SS exists, thus delaying both diagnosis and initiation of treatment. Histopathologic examination may be helpful, but in many cases it is nonspecific, as are serologic markers. Neuroradiological confirmation of involvement usually is the confirmatory feature in many patients with late-stage diagnosis.² A diagnostic schematic for SS, which was first described by Daoud et al,² illustrates classification of symptoms and aids in diagnosis. A working diagnosis of idiopathic livedo racemosa is made after ruling out other causes of SS in a patient with nonspecific biopsy findings and negative magnetic resonance imaging results with prodromal symptoms. The prognosis for such patients progressing to full SS is unknown with or without management using anticoagulant therapy.

Conclusion

Early diagnosis of livedo racemosa and SS is essential, as prevention of cerebrovascular accidents, myocardial infarction, and other thromboembolic diseases can be minimized by attacking risk factors such as smoking, taking oral contraceptive pills, becoming pregnant,⁹ and by initiating either antiplatelet or anticoagulation treatments. These treatments have been shown to delay the development of neurovascular damage and early-onset dementia. We present this case to demonstrate the variability of early-presenting symptoms in idiopathic livedo racemosa. Recognizing some of the early manifestations can lead to early diagnosis and initiation of treatment.

Sneddon syndrome (SS) was first described in 1965 in patients with persistent livedo racemosa and neurological events.¹ Because the other manifestations of SS are nonspecific (eg, hypertension, cardiac valvulopathy, arterial and venous occlusion), the diagnosis often is delayed. Many patients who experience prodromal neurologic symptoms such as headaches, depression, anxiety, dizziness, and neuropathy often present to a physician prior to developing ischemic brain manifestations² but seldom receive the correct diagnosis. Onset of cerebral occlusive events typically occurs in patients younger than 45 years and may present as a transient ischemic attack, stroke, or intracranial hemorrhage.³ The disease is more prevalent in females than males (2:1 ratio). The exact pathogenesis of SS is still unknown, and although it has been thought of as a separate entity from systemic lupus erythematosus and other antiphospholipid disorders, it has been postulated that an immunological dysfunction damages vessel walls leading to thrombosis.

Cutaneous findings associated with SS involve small- to medium-sized dermal-subdermal arteries. Histopathology in some patients demonstrates proliferation of the endothelium and fibrin deposits with subsequent obliteration of involved arteries.⁴ In many patients including our patient, histopathologic examination of involved skin fails to show specific abnormalities.¹ Zelger et al⁵ reported the sequence of histopathologic skin events in a series of antiphospholipid-negative SS patients. The authors reported that only small arteries at the dermis-subcutis junction were involved and a progression of endothelial dysfunction was observed. The authors believed there were several nonspecific stages prior to fibrin occlusion of involved arteries.⁵ Stage I involved loosening of endothelial cells with nonspecific perivascular lymphocytic infiltration with perivascular inflammation and lymphocytic infiltration representing the prime mover of the disease.^5,6 This stage is thought to be short lived, thus the reason why it has gone undetected for many years in SS patients. Stages II to IV progress through fibrin deposition and occlusion.⁵ Histological features of stages I to II have not been reported because of late diagnosis of SS. Stage I patients typically present with an average duration of symptoms of 6 months with few neurologic symptoms, the most common being paresthesia of the legs.⁵

Case Report

A 37-year-old woman with epigastric tenderness on the left side and splenomegaly seen on computed tomography was referred by a hematologist for evaluation of a reticular rash on the left side of the flank of 9 months’ duration with a presumed diagnosis of focal melanoderma. Her medical history was remarkable for a congenital ventricular septal defect and coarctation of the aorta, as well as endometriosis, myalgia, and joint stiffness that had all developed over the last year. Her medical history also was remarkable for nephrolithiasis, irritable bowel syndrome, and chronic sinusitis, as well as psychiatric depression and anxiety disorders. She recently had been diagnosed with moderate hypertension and had experienced difficulty getting pregnant for the last several years with 3 consecutive miscarriages in the first trimester. Neurologic symptoms included neuropathy involving the feet, intermittent paresthesia of the legs, and a history of chronic migraine headaches for several months.

Dermatologic examination revealed a slightly overweight woman with a 25×30-cm dusky, erythematous, irregular, netlike pattern on the left side of the upper and lower trunk (Figure 1). Extensive livedo racemosa was not altered by changes in temperature and had been unchanged for more than 9 months. There were no signs of pruritus or ulcerations, and areas of livedo racemosa were slightly tender to palpation.

We performed 2 sets of three 4-mm biopsies. The first set targeted areas within the violaceous pattern, while the second set targeted areas of normal tissue between the mottled areas. All 6 specimens demonstrated superficial perivascular lymphocytic infiltrate with no evidence of vasculitis or connective tissue disease. The vessels showed no microthrombi or surrounding fibrosis. No eosinophils were identified within the epidermis. There was no evidence of increased dermal mucin. Both the superficial and deep vascular plexuses were unremarkable and showed no evidence of damage to the walls (Figure 2).

To rule out other possible causes of livedo racemosa, complete blood cell count, comprehensive metabolic panel, coagulation profile, lipase test, urinalysis, serologic testing, and immunologic workup were performed. Lipase was within reference range. The complete blood cell count revealed mild anemia, while the rest of the values were within reference range. An immunologic workup included Sjögren syndrome antigen A, Sjögren syndrome antigen B, anticardiolipin antibodies, and antinuclear antibody, which were all negative. Family history was remarkable for first-degree relatives with systemic lupus erythematosus and Crohn disease.

Computed tomography revealed enlargement of the spleen, as well as periaortic, portacaval, and porta hepatis lymphadenopathy. Based on the laboratory findings and clinical presentation as well as the patient’s medical history, the diagnosis of exclusion was idiopathic livedo racemosa with unknown progression to full-blown SS. The patient did not meet the current diagnostic criteria for SS, and her immunologic studies failed to confirm any present antibodies, but involvement of the reticuloendothelial system pointed to production of antibodies that were not yet detectable on laboratory testing.

Comment

More than 50 years after the first case of SS was diagnosed, better laboratory workup is available and more information is known about the pathophysiology. Sneddon syndrome is a rare disorder, affecting only approximately 4 patients per million each year worldwide. Seronegative antiphospholipid antibody syndrome (SNAPS) describes patients with clinical presentations of antiphospholipid syndrome (APS) without detectable serological markers.⁷ Antiphospholipid-negative SS, which was seen in our patient, would be categorized under SNAPS. A PubMed search of articles indexed for MEDLINE using the terms livedo racemosa, Sneddon syndrome, and SNAPS and splenomegaly revealed there currently are no known cases of SNAPS that have been reported with splenomegaly and lymphadenopathy. Our patient presented with the following clinical features of SS: livedo racemosa, history of miscarriage, psychiatric disturbances, and hypertension. Surprisingly, biopsies from affected skin did not show any fibrin deposition or microthrombi but did reveal perivascular lymphocytic infiltrations. Magnetic resonance imaging did not show any pathological lesions or vascular changes.

Sneddon syndrome and APS share a common pathway to occlusive arteriolopathy for which 4 stages have been described by Zelger et al.⁵ Stage I involves a nonspecific Langerhans cell infiltrate with polymorphonuclear leukocytes. The tunica media and elastic lamina usually are unaltered at this early stage, while the surrounding connective tissue may appear edematous.⁵ This early stage of histopathology has not been evaluated in SS patients, primarily because of delay of diagnosis. Late stages III and IV will show fibrin deposition and shrinkage of affected vessels.⁷

A PubMed search using the terms Sneddon syndrome, lymphadenopathy and livedo racemosa, and Sneddon syndrome and lymphadenopathy revealed that splenomegaly and lymphadenopathy have not been reported in patients with SS. In patients with antiphospholipid-negative SS, one can assume that antibodies to other phospholipids not tested must exist because of striking similarities between APS and antiphospholipid-negative SS.⁸ Although our patient did not test positive for any of these antibodies, she did present with lymphadenopathy and splenic enlargement, leading us to believe that involvement of the reticuloendothelial system may be a feature of SS that has not been previously reported. Further studies are required to name specific antigens responsible for clinical manifestations in SS.

Currently, no single diagnostic test for SS exists, thus delaying both diagnosis and initiation of treatment. Histopathologic examination may be helpful, but in many cases it is nonspecific, as are serologic markers. Neuroradiological confirmation of involvement usually is the confirmatory feature in many patients with late-stage diagnosis.² A diagnostic schematic for SS, which was first described by Daoud et al,² illustrates classification of symptoms and aids in diagnosis. A working diagnosis of idiopathic livedo racemosa is made after ruling out other causes of SS in a patient with nonspecific biopsy findings and negative magnetic resonance imaging results with prodromal symptoms. The prognosis for such patients progressing to full SS is unknown with or without management using anticoagulant therapy.

Conclusion

Early diagnosis of livedo racemosa and SS is essential, as prevention of cerebrovascular accidents, myocardial infarction, and other thromboembolic diseases can be minimized by attacking risk factors such as smoking, taking oral contraceptive pills, becoming pregnant,⁹ and by initiating either antiplatelet or anticoagulation treatments. These treatments have been shown to delay the development of neurovascular damage and early-onset dementia. We present this case to demonstrate the variability of early-presenting symptoms in idiopathic livedo racemosa. Recognizing some of the early manifestations can lead to early diagnosis and initiation of treatment.

Sneddon syndrome (SS) was first described in 1965 in patients with persistent livedo racemosa and neurological events.¹ Because the other manifestations of SS are nonspecific (eg, hypertension, cardiac valvulopathy, arterial and venous occlusion), the diagnosis often is delayed. Many patients who experience prodromal neurologic symptoms such as headaches, depression, anxiety, dizziness, and neuropathy often present to a physician prior to developing ischemic brain manifestations² but seldom receive the correct diagnosis. Onset of cerebral occlusive events typically occurs in patients younger than 45 years and may present as a transient ischemic attack, stroke, or intracranial hemorrhage.³ The disease is more prevalent in females than males (2:1 ratio). The exact pathogenesis of SS is still unknown, and although it has been thought of as a separate entity from systemic lupus erythematosus and other antiphospholipid disorders, it has been postulated that an immunological dysfunction damages vessel walls leading to thrombosis.

Cutaneous findings associated with SS involve small- to medium-sized dermal-subdermal arteries. Histopathology in some patients demonstrates proliferation of the endothelium and fibrin deposits with subsequent obliteration of involved arteries.⁴ In many patients including our patient, histopathologic examination of involved skin fails to show specific abnormalities.¹ Zelger et al⁵ reported the sequence of histopathologic skin events in a series of antiphospholipid-negative SS patients. The authors reported that only small arteries at the dermis-subcutis junction were involved and a progression of endothelial dysfunction was observed. The authors believed there were several nonspecific stages prior to fibrin occlusion of involved arteries.⁵ Stage I involved loosening of endothelial cells with nonspecific perivascular lymphocytic infiltration with perivascular inflammation and lymphocytic infiltration representing the prime mover of the disease.^5,6 This stage is thought to be short lived, thus the reason why it has gone undetected for many years in SS patients. Stages II to IV progress through fibrin deposition and occlusion.⁵ Histological features of stages I to II have not been reported because of late diagnosis of SS. Stage I patients typically present with an average duration of symptoms of 6 months with few neurologic symptoms, the most common being paresthesia of the legs.⁵

Case Report

A 37-year-old woman with epigastric tenderness on the left side and splenomegaly seen on computed tomography was referred by a hematologist for evaluation of a reticular rash on the left side of the flank of 9 months’ duration with a presumed diagnosis of focal melanoderma. Her medical history was remarkable for a congenital ventricular septal defect and coarctation of the aorta, as well as endometriosis, myalgia, and joint stiffness that had all developed over the last year. Her medical history also was remarkable for nephrolithiasis, irritable bowel syndrome, and chronic sinusitis, as well as psychiatric depression and anxiety disorders. She recently had been diagnosed with moderate hypertension and had experienced difficulty getting pregnant for the last several years with 3 consecutive miscarriages in the first trimester. Neurologic symptoms included neuropathy involving the feet, intermittent paresthesia of the legs, and a history of chronic migraine headaches for several months.

Dermatologic examination revealed a slightly overweight woman with a 25×30-cm dusky, erythematous, irregular, netlike pattern on the left side of the upper and lower trunk (Figure 1). Extensive livedo racemosa was not altered by changes in temperature and had been unchanged for more than 9 months. There were no signs of pruritus or ulcerations, and areas of livedo racemosa were slightly tender to palpation.

We performed 2 sets of three 4-mm biopsies. The first set targeted areas within the violaceous pattern, while the second set targeted areas of normal tissue between the mottled areas. All 6 specimens demonstrated superficial perivascular lymphocytic infiltrate with no evidence of vasculitis or connective tissue disease. The vessels showed no microthrombi or surrounding fibrosis. No eosinophils were identified within the epidermis. There was no evidence of increased dermal mucin. Both the superficial and deep vascular plexuses were unremarkable and showed no evidence of damage to the walls (Figure 2).

To rule out other possible causes of livedo racemosa, complete blood cell count, comprehensive metabolic panel, coagulation profile, lipase test, urinalysis, serologic testing, and immunologic workup were performed. Lipase was within reference range. The complete blood cell count revealed mild anemia, while the rest of the values were within reference range. An immunologic workup included Sjögren syndrome antigen A, Sjögren syndrome antigen B, anticardiolipin antibodies, and antinuclear antibody, which were all negative. Family history was remarkable for first-degree relatives with systemic lupus erythematosus and Crohn disease.

Computed tomography revealed enlargement of the spleen, as well as periaortic, portacaval, and porta hepatis lymphadenopathy. Based on the laboratory findings and clinical presentation as well as the patient’s medical history, the diagnosis of exclusion was idiopathic livedo racemosa with unknown progression to full-blown SS. The patient did not meet the current diagnostic criteria for SS, and her immunologic studies failed to confirm any present antibodies, but involvement of the reticuloendothelial system pointed to production of antibodies that were not yet detectable on laboratory testing.

Comment

More than 50 years after the first case of SS was diagnosed, better laboratory workup is available and more information is known about the pathophysiology. Sneddon syndrome is a rare disorder, affecting only approximately 4 patients per million each year worldwide. Seronegative antiphospholipid antibody syndrome (SNAPS) describes patients with clinical presentations of antiphospholipid syndrome (APS) without detectable serological markers.⁷ Antiphospholipid-negative SS, which was seen in our patient, would be categorized under SNAPS. A PubMed search of articles indexed for MEDLINE using the terms livedo racemosa, Sneddon syndrome, and SNAPS and splenomegaly revealed there currently are no known cases of SNAPS that have been reported with splenomegaly and lymphadenopathy. Our patient presented with the following clinical features of SS: livedo racemosa, history of miscarriage, psychiatric disturbances, and hypertension. Surprisingly, biopsies from affected skin did not show any fibrin deposition or microthrombi but did reveal perivascular lymphocytic infiltrations. Magnetic resonance imaging did not show any pathological lesions or vascular changes.

Sneddon syndrome and APS share a common pathway to occlusive arteriolopathy for which 4 stages have been described by Zelger et al.⁵ Stage I involves a nonspecific Langerhans cell infiltrate with polymorphonuclear leukocytes. The tunica media and elastic lamina usually are unaltered at this early stage, while the surrounding connective tissue may appear edematous.⁵ This early stage of histopathology has not been evaluated in SS patients, primarily because of delay of diagnosis. Late stages III and IV will show fibrin deposition and shrinkage of affected vessels.⁷

A PubMed search using the terms Sneddon syndrome, lymphadenopathy and livedo racemosa, and Sneddon syndrome and lymphadenopathy revealed that splenomegaly and lymphadenopathy have not been reported in patients with SS. In patients with antiphospholipid-negative SS, one can assume that antibodies to other phospholipids not tested must exist because of striking similarities between APS and antiphospholipid-negative SS.⁸ Although our patient did not test positive for any of these antibodies, she did present with lymphadenopathy and splenic enlargement, leading us to believe that involvement of the reticuloendothelial system may be a feature of SS that has not been previously reported. Further studies are required to name specific antigens responsible for clinical manifestations in SS.

Currently, no single diagnostic test for SS exists, thus delaying both diagnosis and initiation of treatment. Histopathologic examination may be helpful, but in many cases it is nonspecific, as are serologic markers. Neuroradiological confirmation of involvement usually is the confirmatory feature in many patients with late-stage diagnosis.² A diagnostic schematic for SS, which was first described by Daoud et al,² illustrates classification of symptoms and aids in diagnosis. A working diagnosis of idiopathic livedo racemosa is made after ruling out other causes of SS in a patient with nonspecific biopsy findings and negative magnetic resonance imaging results with prodromal symptoms. The prognosis for such patients progressing to full SS is unknown with or without management using anticoagulant therapy.

Conclusion

Early diagnosis of livedo racemosa and SS is essential, as prevention of cerebrovascular accidents, myocardial infarction, and other thromboembolic diseases can be minimized by attacking risk factors such as smoking, taking oral contraceptive pills, becoming pregnant,⁹ and by initiating either antiplatelet or anticoagulation treatments. These treatments have been shown to delay the development of neurovascular damage and early-onset dementia. We present this case to demonstrate the variability of early-presenting symptoms in idiopathic livedo racemosa. Recognizing some of the early manifestations can lead to early diagnosis and initiation of treatment.

Blastomycosis
Blastomycosis is caused by Blastomyces dermatitidis, which is endemic in the Midwestern and southeastern United States where it occurs environmentally in wood and soil. Unlike many fungal infections, blastomycosis most often develops in immunocompetent hosts. Infection is usually acquired via inhalation,¹ and cutaneous disease typically is secondary to pulmonary infection. Although not common, traumatic inoculation also can cause cutaneous blastomycosis. Skin lesions include crusted verrucous nodules and plaques with elevated borders.^1,2 Histologic features include pseudoepitheliomatous hyperplasia with intraepidermal neutrophilic microabscesses (Figure 1), and a neutrophilic and granulomatous dermal infiltrate. Organisms often are found within histiocytes (quiz image) or small abscesses. The yeasts usually are 8 to 15 µm in diameter with a thick cell wall and occasionally display broad-based budding.

Chromoblastomycosis is caused by dematiaceous (pigmented) fungi, including Fonsecaea, Phialophora, Cladophialophora, and Rhinocladiella species,³ which are present in soil and vegetable debris in tropical and subtropical regions. Infection typically occurs in the foot or lower leg from traumatic inoculation, such as a thorn or splinter injury.² Histologically, chromoblastomycosis is characterized by pseudoepitheliomatous hyperplasia; suppurative and granulomatous dermatitis; and sclerotic (Medlar) bodies, which are 5 to 12 µm in diameter, round, brown, sometimes septate cells resembling copper pennies (Figure 2).²

Coccidioidomycosis is caused by Coccidioides immitis, which is found in soil in the southwestern United States. Infection most often occurs via inhalation of airborne arthrospores.² Cutaneous lesions occasionally are observed following dissemination or rarely following primary inoculation injury. They may present as papules, nodules, pustules, plaques, and ulcers, with the face being the most commonly affected site.¹ Histologically, coccidioidomycosis is characterized by pseudoepitheliomatous hyperplasia, suppurative and granulomatous dermatitis, and large spherules (up to 100 µm in diameter) containing numerous small endospores (Figure 3).

Cryptococcosis is caused by Cryptococcus neoformans, a fungus found in soil, fruit, and pigeon droppings throughout the world.^2,3 The most common route of infection is via the respiratory tract. Systemic spread and central nervous system involvement may occur in immunocompromised hosts.² Skin involvement is uncommon and may present on the head and neck with umbilicated papules, pustules, nodules, plaques, or ulcers. Histologically, Cryptococcus is a spherical yeast, often 4 to 20 µm in diameter. Replication is by narrow-based budding. A characteristic feature is a mucoid capsule, which retracts during processing, leaving a clear space around the yeast (Figure 4). When present, the mucoid capsule can be highlighted on mucicarmine or Alcian blue staining. Histologic variants of cryptococcosis include granulomatous (high host immune response), gelatinous (low host immune response), and suppurative types.³  

Blastomycosis
Blastomycosis is caused by Blastomyces dermatitidis, which is endemic in the Midwestern and southeastern United States where it occurs environmentally in wood and soil. Unlike many fungal infections, blastomycosis most often develops in immunocompetent hosts. Infection is usually acquired via inhalation,¹ and cutaneous disease typically is secondary to pulmonary infection. Although not common, traumatic inoculation also can cause cutaneous blastomycosis. Skin lesions include crusted verrucous nodules and plaques with elevated borders.^1,2 Histologic features include pseudoepitheliomatous hyperplasia with intraepidermal neutrophilic microabscesses (Figure 1), and a neutrophilic and granulomatous dermal infiltrate. Organisms often are found within histiocytes (quiz image) or small abscesses. The yeasts usually are 8 to 15 µm in diameter with a thick cell wall and occasionally display broad-based budding.

Chromoblastomycosis is caused by dematiaceous (pigmented) fungi, including Fonsecaea, Phialophora, Cladophialophora, and Rhinocladiella species,³ which are present in soil and vegetable debris in tropical and subtropical regions. Infection typically occurs in the foot or lower leg from traumatic inoculation, such as a thorn or splinter injury.² Histologically, chromoblastomycosis is characterized by pseudoepitheliomatous hyperplasia; suppurative and granulomatous dermatitis; and sclerotic (Medlar) bodies, which are 5 to 12 µm in diameter, round, brown, sometimes septate cells resembling copper pennies (Figure 2).²

Coccidioidomycosis is caused by Coccidioides immitis, which is found in soil in the southwestern United States. Infection most often occurs via inhalation of airborne arthrospores.² Cutaneous lesions occasionally are observed following dissemination or rarely following primary inoculation injury. They may present as papules, nodules, pustules, plaques, and ulcers, with the face being the most commonly affected site.¹ Histologically, coccidioidomycosis is characterized by pseudoepitheliomatous hyperplasia, suppurative and granulomatous dermatitis, and large spherules (up to 100 µm in diameter) containing numerous small endospores (Figure 3).

Cryptococcosis is caused by Cryptococcus neoformans, a fungus found in soil, fruit, and pigeon droppings throughout the world.^2,3 The most common route of infection is via the respiratory tract. Systemic spread and central nervous system involvement may occur in immunocompromised hosts.² Skin involvement is uncommon and may present on the head and neck with umbilicated papules, pustules, nodules, plaques, or ulcers. Histologically, Cryptococcus is a spherical yeast, often 4 to 20 µm in diameter. Replication is by narrow-based budding. A characteristic feature is a mucoid capsule, which retracts during processing, leaving a clear space around the yeast (Figure 4). When present, the mucoid capsule can be highlighted on mucicarmine or Alcian blue staining. Histologic variants of cryptococcosis include granulomatous (high host immune response), gelatinous (low host immune response), and suppurative types.³  

Blastomycosis
Blastomycosis is caused by Blastomyces dermatitidis, which is endemic in the Midwestern and southeastern United States where it occurs environmentally in wood and soil. Unlike many fungal infections, blastomycosis most often develops in immunocompetent hosts. Infection is usually acquired via inhalation,¹ and cutaneous disease typically is secondary to pulmonary infection. Although not common, traumatic inoculation also can cause cutaneous blastomycosis. Skin lesions include crusted verrucous nodules and plaques with elevated borders.^1,2 Histologic features include pseudoepitheliomatous hyperplasia with intraepidermal neutrophilic microabscesses (Figure 1), and a neutrophilic and granulomatous dermal infiltrate. Organisms often are found within histiocytes (quiz image) or small abscesses. The yeasts usually are 8 to 15 µm in diameter with a thick cell wall and occasionally display broad-based budding.

Chromoblastomycosis is caused by dematiaceous (pigmented) fungi, including Fonsecaea, Phialophora, Cladophialophora, and Rhinocladiella species,³ which are present in soil and vegetable debris in tropical and subtropical regions. Infection typically occurs in the foot or lower leg from traumatic inoculation, such as a thorn or splinter injury.² Histologically, chromoblastomycosis is characterized by pseudoepitheliomatous hyperplasia; suppurative and granulomatous dermatitis; and sclerotic (Medlar) bodies, which are 5 to 12 µm in diameter, round, brown, sometimes septate cells resembling copper pennies (Figure 2).²

Coccidioidomycosis is caused by Coccidioides immitis, which is found in soil in the southwestern United States. Infection most often occurs via inhalation of airborne arthrospores.² Cutaneous lesions occasionally are observed following dissemination or rarely following primary inoculation injury. They may present as papules, nodules, pustules, plaques, and ulcers, with the face being the most commonly affected site.¹ Histologically, coccidioidomycosis is characterized by pseudoepitheliomatous hyperplasia, suppurative and granulomatous dermatitis, and large spherules (up to 100 µm in diameter) containing numerous small endospores (Figure 3).

Cryptococcosis is caused by Cryptococcus neoformans, a fungus found in soil, fruit, and pigeon droppings throughout the world.^2,3 The most common route of infection is via the respiratory tract. Systemic spread and central nervous system involvement may occur in immunocompromised hosts.² Skin involvement is uncommon and may present on the head and neck with umbilicated papules, pustules, nodules, plaques, or ulcers. Histologically, Cryptococcus is a spherical yeast, often 4 to 20 µm in diameter. Replication is by narrow-based budding. A characteristic feature is a mucoid capsule, which retracts during processing, leaving a clear space around the yeast (Figure 4). When present, the mucoid capsule can be highlighted on mucicarmine or Alcian blue staining. Histologic variants of cryptococcosis include granulomatous (high host immune response), gelatinous (low host immune response), and suppurative types.³  

Sea urchin injuries are commonly seen in coastal regions near both warm and cold salt water with frequent recreational water activities or fishing. Sea urchins belong to the class Echinoidea with approximately 600 species, of which roughly 80 are poisonous to humans.^1,2 When a human comes in contact with a sea urchin, the spines of the sea urchin (made of calcium carbonate) can penetrate the skin and break off from the sea urchin, becoming embedded in the skin. Injuries from sea urchin spines are most commonly seen on the hands and feet, as the likelihood of contact with a sea urchin is greater on these sites. The severity of sea urchin spine injuries can vary widely, from minimal local trauma and pain to arthritis, synovitis, and occasionally systemic illness.^1,3 It is important to recognize the wide variety of responses to sea urchin spine injuries and the impact of prompt treatment. Many published reports on injuries from sea urchin spines describe arthritis and synovitis from spines in the joints.^1,2,4-6 Fewer reports discuss nonjoint injuries and the dermatologic aspects of sea urchin spine injuries.^3,7,8 We pre-sent a case of a patient with a puncture injury from sea urchin spines that resulted in painful granulomas.

Case Report

A 29-year-old otherwise healthy man was referred to our dermatology clinic by the university student health center due to continued pain in the right thigh. Five weeks prior to presentation to the student health center, the patient had fallen on a sea urchin while snorkeling in Hawaii. Sea urchin spines became lodged in the right thigh, some of which were removed in a local medical clinic in Hawaii. He was given oral antibiotics prior to his return home. A plain film radiograph of the affected area ordered by the student health center showed several punctate and linear densities in the lateral aspect of the right mid thigh (Figure 1). These findings were consistent with sea urchin spines within the superficial soft tissues of the lateral thigh.

At the time of presentation to our dermatology clinic, the patient reported sharp intermittent pain localized to the right thigh. The patient denied any fever, chills, or pain in the joints. On physical examination, there were several firm nodules on the right thigh, ranging from 4 to 20 mm in diameter (Figure 2). The nodules were tender to palpation with some surrounding edema. Drainage was not noted. Several scars were visible at sites of the original puncture injuries and removal of the spines.

Two 6-mm punch biopsies were performed on representative nodules on the right thigh for histopathologic examination. Along with the biopsy tissue, firm, brown-black, linear foreign bodies consistent with sea urchin spines were extracted with forceps (Figure 3). Histopathologic examination revealed a dense, diffuse, mixed inflammatory cell infiltrate in the dermis predominantly composed of lymphocytes, histiocytes, and numerous eosinophils. Proliferation of small vessels was noted. In one of the biopsies, small fragments of necrotic tissue were present. These findings were consistent with granulomatous inflammation and granulation tissue due to a foreign body.

At the time of suture removal 2 weeks later, the biopsied areas were well healed with minimal erythema. The patient reported decreased pain in the involved areas. He was not seen in clinic again due to resolution of the nodules and associated pain.

Comment

Sea urchin spine injuries are commonly seen in coastal regions with frequent participation in recreational and occupational water activities. A wide variety of responses can be seen in sea urchin spine injuries. There generally are 2 types of cutaneous reaction patterns to sea urchin spines: a primary initial reaction and a secondary delayed/granulomatous reaction. When the spines initially penetrate the skin, the primary initial reaction consists of sharp localized pain that worsens with applied pressure. In addition to pain, bleeding, erythema, edema, and myalgia can occur.³ These symptoms typically subside a few hours after complete removal of the spines from the skin.⁶ If some spines remain in the skin, a secondary delayed/granulomatous reaction can occur, which can lead to the formation of granulomas that can manifest as nodules or papules and can be diffuse.

Many patients may think their painful encounter with a sea urchin was just an unfortunate event, but depending on the location of the injury, more serious extracutaneous reactions and chronic symptoms may occur. Some cases have described the development of arthritis and synovitis from the implantation of spines into joints.^1,2,4-6 Other extracutaneous complications include neuropathy and paresthesia, local bone destruction, radiating pain, muscular weakness, and hypotension.³

The severity of the injury also can depend on the sea urchin species and the number of spines implanted. There are approximately 80 poisonous sea urchin species possessing toxins in venomous spines, resulting in edema and change in the leukocyte-endothelial interaction.⁹ Substances identified in the spines include proteins, steroids, serotonin, histamine, and glycosides.^3,9 The number of spines implanted, particularly the number of venomous spines, can lead to more severe complications. Penetration of 15 or more venomous spines can commonly lead to extracutaneous symptoms.³ Another concern, irrespective of species type, is the potential for secondary infection associated with the spine penetration or implantation into the skin. Mycobacterium marinum infections have been reported in some sea urchin granulomas,¹⁰ as well as fungal infection, bacterial infection, and tetanus.³

The diagnosis of sea urchin spine injuries starts with a thorough history and physical examination. A positive history of sea urchin contact suggests the diagnosis, and radiographs can be useful to find the location of the spine(s), especially if there are no visible nodules on the skin. However, small fragments of spine may not be completely observed on plain radiographs. Any signs or symptoms of infection should prompt a culture for confirmation and guidance for management. Cutaneous biopsies can be helpful for both diagnosis confirmation and symptomatic relief. Reported cases have described granulomatous reactions in the vast majority of the histologic specimens, with necrosis an additional common finding.^7,8 Sea urchin granulomas can be of varying types, the majority being foreign-body and sarcoid types.^3,6,7

Treatment of sea urchin spine injuries primarily involves removal of the spines by a physician. Patients may soak the affected areas in warm water prior to the removal of the spines to aid in pain relief. Surgical removal with local anesthesia and cutaneous extraction is a common treatment method, and more extensive surgical removal of the spines is another option, especially in areas around the joints.² The use of liquid nitrogen or skin punch biopsy also have been described as possible methods to remove the spines.^11,12

Conclusion

Sea urchin spine injuries can result in a wide range of cutaneous and systemic complications. Prompt diagnosis and treatment to remove the sea urchin spines can lessen the associated pain and is important in the prevention of more serious complications.

Sea urchin injuries are commonly seen in coastal regions near both warm and cold salt water with frequent recreational water activities or fishing. Sea urchins belong to the class Echinoidea with approximately 600 species, of which roughly 80 are poisonous to humans.^1,2 When a human comes in contact with a sea urchin, the spines of the sea urchin (made of calcium carbonate) can penetrate the skin and break off from the sea urchin, becoming embedded in the skin. Injuries from sea urchin spines are most commonly seen on the hands and feet, as the likelihood of contact with a sea urchin is greater on these sites. The severity of sea urchin spine injuries can vary widely, from minimal local trauma and pain to arthritis, synovitis, and occasionally systemic illness.^1,3 It is important to recognize the wide variety of responses to sea urchin spine injuries and the impact of prompt treatment. Many published reports on injuries from sea urchin spines describe arthritis and synovitis from spines in the joints.^1,2,4-6 Fewer reports discuss nonjoint injuries and the dermatologic aspects of sea urchin spine injuries.^3,7,8 We pre-sent a case of a patient with a puncture injury from sea urchin spines that resulted in painful granulomas.

Case Report

A 29-year-old otherwise healthy man was referred to our dermatology clinic by the university student health center due to continued pain in the right thigh. Five weeks prior to presentation to the student health center, the patient had fallen on a sea urchin while snorkeling in Hawaii. Sea urchin spines became lodged in the right thigh, some of which were removed in a local medical clinic in Hawaii. He was given oral antibiotics prior to his return home. A plain film radiograph of the affected area ordered by the student health center showed several punctate and linear densities in the lateral aspect of the right mid thigh (Figure 1). These findings were consistent with sea urchin spines within the superficial soft tissues of the lateral thigh.

At the time of presentation to our dermatology clinic, the patient reported sharp intermittent pain localized to the right thigh. The patient denied any fever, chills, or pain in the joints. On physical examination, there were several firm nodules on the right thigh, ranging from 4 to 20 mm in diameter (Figure 2). The nodules were tender to palpation with some surrounding edema. Drainage was not noted. Several scars were visible at sites of the original puncture injuries and removal of the spines.

Two 6-mm punch biopsies were performed on representative nodules on the right thigh for histopathologic examination. Along with the biopsy tissue, firm, brown-black, linear foreign bodies consistent with sea urchin spines were extracted with forceps (Figure 3). Histopathologic examination revealed a dense, diffuse, mixed inflammatory cell infiltrate in the dermis predominantly composed of lymphocytes, histiocytes, and numerous eosinophils. Proliferation of small vessels was noted. In one of the biopsies, small fragments of necrotic tissue were present. These findings were consistent with granulomatous inflammation and granulation tissue due to a foreign body.

At the time of suture removal 2 weeks later, the biopsied areas were well healed with minimal erythema. The patient reported decreased pain in the involved areas. He was not seen in clinic again due to resolution of the nodules and associated pain.

Comment

Sea urchin spine injuries are commonly seen in coastal regions with frequent participation in recreational and occupational water activities. A wide variety of responses can be seen in sea urchin spine injuries. There generally are 2 types of cutaneous reaction patterns to sea urchin spines: a primary initial reaction and a secondary delayed/granulomatous reaction. When the spines initially penetrate the skin, the primary initial reaction consists of sharp localized pain that worsens with applied pressure. In addition to pain, bleeding, erythema, edema, and myalgia can occur.³ These symptoms typically subside a few hours after complete removal of the spines from the skin.⁶ If some spines remain in the skin, a secondary delayed/granulomatous reaction can occur, which can lead to the formation of granulomas that can manifest as nodules or papules and can be diffuse.

Many patients may think their painful encounter with a sea urchin was just an unfortunate event, but depending on the location of the injury, more serious extracutaneous reactions and chronic symptoms may occur. Some cases have described the development of arthritis and synovitis from the implantation of spines into joints.^1,2,4-6 Other extracutaneous complications include neuropathy and paresthesia, local bone destruction, radiating pain, muscular weakness, and hypotension.³

The severity of the injury also can depend on the sea urchin species and the number of spines implanted. There are approximately 80 poisonous sea urchin species possessing toxins in venomous spines, resulting in edema and change in the leukocyte-endothelial interaction.⁹ Substances identified in the spines include proteins, steroids, serotonin, histamine, and glycosides.^3,9 The number of spines implanted, particularly the number of venomous spines, can lead to more severe complications. Penetration of 15 or more venomous spines can commonly lead to extracutaneous symptoms.³ Another concern, irrespective of species type, is the potential for secondary infection associated with the spine penetration or implantation into the skin. Mycobacterium marinum infections have been reported in some sea urchin granulomas,¹⁰ as well as fungal infection, bacterial infection, and tetanus.³

The diagnosis of sea urchin spine injuries starts with a thorough history and physical examination. A positive history of sea urchin contact suggests the diagnosis, and radiographs can be useful to find the location of the spine(s), especially if there are no visible nodules on the skin. However, small fragments of spine may not be completely observed on plain radiographs. Any signs or symptoms of infection should prompt a culture for confirmation and guidance for management. Cutaneous biopsies can be helpful for both diagnosis confirmation and symptomatic relief. Reported cases have described granulomatous reactions in the vast majority of the histologic specimens, with necrosis an additional common finding.^7,8 Sea urchin granulomas can be of varying types, the majority being foreign-body and sarcoid types.^3,6,7

Treatment of sea urchin spine injuries primarily involves removal of the spines by a physician. Patients may soak the affected areas in warm water prior to the removal of the spines to aid in pain relief. Surgical removal with local anesthesia and cutaneous extraction is a common treatment method, and more extensive surgical removal of the spines is another option, especially in areas around the joints.² The use of liquid nitrogen or skin punch biopsy also have been described as possible methods to remove the spines.^11,12

Conclusion

Sea urchin spine injuries can result in a wide range of cutaneous and systemic complications. Prompt diagnosis and treatment to remove the sea urchin spines can lessen the associated pain and is important in the prevention of more serious complications.

Sea urchin injuries are commonly seen in coastal regions near both warm and cold salt water with frequent recreational water activities or fishing. Sea urchins belong to the class Echinoidea with approximately 600 species, of which roughly 80 are poisonous to humans.^1,2 When a human comes in contact with a sea urchin, the spines of the sea urchin (made of calcium carbonate) can penetrate the skin and break off from the sea urchin, becoming embedded in the skin. Injuries from sea urchin spines are most commonly seen on the hands and feet, as the likelihood of contact with a sea urchin is greater on these sites. The severity of sea urchin spine injuries can vary widely, from minimal local trauma and pain to arthritis, synovitis, and occasionally systemic illness.^1,3 It is important to recognize the wide variety of responses to sea urchin spine injuries and the impact of prompt treatment. Many published reports on injuries from sea urchin spines describe arthritis and synovitis from spines in the joints.^1,2,4-6 Fewer reports discuss nonjoint injuries and the dermatologic aspects of sea urchin spine injuries.^3,7,8 We pre-sent a case of a patient with a puncture injury from sea urchin spines that resulted in painful granulomas.

Case Report

A 29-year-old otherwise healthy man was referred to our dermatology clinic by the university student health center due to continued pain in the right thigh. Five weeks prior to presentation to the student health center, the patient had fallen on a sea urchin while snorkeling in Hawaii. Sea urchin spines became lodged in the right thigh, some of which were removed in a local medical clinic in Hawaii. He was given oral antibiotics prior to his return home. A plain film radiograph of the affected area ordered by the student health center showed several punctate and linear densities in the lateral aspect of the right mid thigh (Figure 1). These findings were consistent with sea urchin spines within the superficial soft tissues of the lateral thigh.

At the time of presentation to our dermatology clinic, the patient reported sharp intermittent pain localized to the right thigh. The patient denied any fever, chills, or pain in the joints. On physical examination, there were several firm nodules on the right thigh, ranging from 4 to 20 mm in diameter (Figure 2). The nodules were tender to palpation with some surrounding edema. Drainage was not noted. Several scars were visible at sites of the original puncture injuries and removal of the spines.

Two 6-mm punch biopsies were performed on representative nodules on the right thigh for histopathologic examination. Along with the biopsy tissue, firm, brown-black, linear foreign bodies consistent with sea urchin spines were extracted with forceps (Figure 3). Histopathologic examination revealed a dense, diffuse, mixed inflammatory cell infiltrate in the dermis predominantly composed of lymphocytes, histiocytes, and numerous eosinophils. Proliferation of small vessels was noted. In one of the biopsies, small fragments of necrotic tissue were present. These findings were consistent with granulomatous inflammation and granulation tissue due to a foreign body.

At the time of suture removal 2 weeks later, the biopsied areas were well healed with minimal erythema. The patient reported decreased pain in the involved areas. He was not seen in clinic again due to resolution of the nodules and associated pain.

Comment

Sea urchin spine injuries are commonly seen in coastal regions with frequent participation in recreational and occupational water activities. A wide variety of responses can be seen in sea urchin spine injuries. There generally are 2 types of cutaneous reaction patterns to sea urchin spines: a primary initial reaction and a secondary delayed/granulomatous reaction. When the spines initially penetrate the skin, the primary initial reaction consists of sharp localized pain that worsens with applied pressure. In addition to pain, bleeding, erythema, edema, and myalgia can occur.³ These symptoms typically subside a few hours after complete removal of the spines from the skin.⁶ If some spines remain in the skin, a secondary delayed/granulomatous reaction can occur, which can lead to the formation of granulomas that can manifest as nodules or papules and can be diffuse.

Many patients may think their painful encounter with a sea urchin was just an unfortunate event, but depending on the location of the injury, more serious extracutaneous reactions and chronic symptoms may occur. Some cases have described the development of arthritis and synovitis from the implantation of spines into joints.^1,2,4-6 Other extracutaneous complications include neuropathy and paresthesia, local bone destruction, radiating pain, muscular weakness, and hypotension.³

The severity of the injury also can depend on the sea urchin species and the number of spines implanted. There are approximately 80 poisonous sea urchin species possessing toxins in venomous spines, resulting in edema and change in the leukocyte-endothelial interaction.⁹ Substances identified in the spines include proteins, steroids, serotonin, histamine, and glycosides.^3,9 The number of spines implanted, particularly the number of venomous spines, can lead to more severe complications. Penetration of 15 or more venomous spines can commonly lead to extracutaneous symptoms.³ Another concern, irrespective of species type, is the potential for secondary infection associated with the spine penetration or implantation into the skin. Mycobacterium marinum infections have been reported in some sea urchin granulomas,¹⁰ as well as fungal infection, bacterial infection, and tetanus.³

The diagnosis of sea urchin spine injuries starts with a thorough history and physical examination. A positive history of sea urchin contact suggests the diagnosis, and radiographs can be useful to find the location of the spine(s), especially if there are no visible nodules on the skin. However, small fragments of spine may not be completely observed on plain radiographs. Any signs or symptoms of infection should prompt a culture for confirmation and guidance for management. Cutaneous biopsies can be helpful for both diagnosis confirmation and symptomatic relief. Reported cases have described granulomatous reactions in the vast majority of the histologic specimens, with necrosis an additional common finding.^7,8 Sea urchin granulomas can be of varying types, the majority being foreign-body and sarcoid types.^3,6,7

Treatment of sea urchin spine injuries primarily involves removal of the spines by a physician. Patients may soak the affected areas in warm water prior to the removal of the spines to aid in pain relief. Surgical removal with local anesthesia and cutaneous extraction is a common treatment method, and more extensive surgical removal of the spines is another option, especially in areas around the joints.² The use of liquid nitrogen or skin punch biopsy also have been described as possible methods to remove the spines.^11,12

Conclusion

Sea urchin spine injuries can result in a wide range of cutaneous and systemic complications. Prompt diagnosis and treatment to remove the sea urchin spines can lessen the associated pain and is important in the prevention of more serious complications.