Cutaneous Anthrax and Its Mimics

Differential Dx of Ulceroglandular Syndromes:  Cutaneous Anthrax  Cutaneous Leishmaniasis  Cat-Scratch Disease  Chancroid  Herpes Simplex  Lymphogranuloma Venereum  Melioidosis  Cutaneous Nocardiosis  Plague  Sporotrichosis  Streptococcal/Staphylococcal Adenitis  Tuberculosis  Tularemia Differential Dx of Ulcer and Eschar:  Cutaneous Anthrax  Antiphospholipid Antibody Syndrome Ulcers  Aspergillosis and Mucormycosis  Brown Recluse Spider Bite  Coumarin and Heparin Necrosis  Cutaneous Leishmaniasis  Ecthyma and Ecthyma Gangrenosum  Factitious Ulcer  Orf/Milkers Nodule  Plague  Rickettsialpox, Scrub Typhus, and Tick Typhus  Tularemia

Cutaneous Anthrax
Fitzpatricks Dermatology in General Medicine. Fifth Edition. Freedberk IM, Eizen, AZ, Wolff, K, Austen KF, Goldsmith LA, Katz SI, Fitzpatrick TB (eds.). New York: The McGraw Hill Companies, Inc; 1999.

Anthrax is caused by Bacillus anthracis, a sporulating, gram-negative bacillus. B. anthracis can be part of the normal soil, and poses a risk to grazing animals. Natural infection occurs when humans become accidentally infected through contact with infected animals or their products. The primary lesion of cutaneous anthrax begins as a painless, pruritic papule that appears 1 to 7 days after inoculation. The papule enlarges, and within 1 to 2 days, small vesicles or a larger, 1- to 2-cm vesicle forms on the papule that is filled with clear or serosanguineous fluid.

Cutaneous Anthrax (continued)

As the vesicle enlarges, satellite vesicles may form. Fluid within the vesicles may contain numerous, large gram-positive bacilli and a paucity of neutrophils. Within 1 to 2 days, the vesicle ruptures, undergoes necrosis, and enlarges, forming painless ulcer covered by a characteristic black eschar. Surrounding the ulcer and eschar is a characteristic, non-pitting, gelatinous edema that appears out of proportion to the size of the ulcer. Symptoms include low-grade fever and malaise. Regional lymphadenopathy is present early on. Clinical characteristics highly suggestive of cutaneous anthrax include: (1) a painless ulcer covered with black eschar (2) surrounding edema out of proportion to the size of the ulcer (3) a paucity of neutrophils in vesicular fluid.

Cutaneous Leishmaniasis

Cutaneous Leishmaniasis
Leishmaniasis is an infection caused by the protozoan parasite belonging to the genus Leishmania. Natural reservoirs are rodents and domesticated dogs, and the vector is the sandfly, a small mosquitolike insect. Ninety percent of all cases of leishmaniasis occur in Saudi Arabia, Iran, Afghanistan, Brazil, and Peru. The disease begins as a small, red, painless papule, usually 2 to 4 weeks after the sandfly bite. The papule enlarges to approximately 2 cm over the next 2 to 4 weeks and becomes dusky red to violaceous in color. The lesion becomes crusted over, and if the crust is removed, a shallow ulcer can be found with a raised, indurated border. Cutaneous leishmaniasis may be associated with small satellite lesions and nodules along the course of the draining lymphatics. After the lesion has been present for 2 months, it ceases expanding and after 3 to 6 months begins to heal, leaving a depressed scar. The number of lesions can range from 1 to 100 or more. Diagnosis depends upon finding the parasites in the skin.

Differential Dx Cutaneous Leishmaniasis

Cutaneous Leishmaniasis
 Patient has traveled to or resides in an endemic area  Lesions slowly evole from papule to ulcer  Nodular lymphangitis may be an associated sign  Eschar is absent

Cutaneous anthrax
 Ulcer and eschar are surrounded by characteristic non-pitting edema  Lesion undergoes rapid progression from papule, vesicle, or bulla, to formation edema, necrotic ulcer, and eschar

Cat-Scratch Disease

Cat-Scratch Disease
Cat-scratch disease is a common, benign condition, most often caused by Bartonella henselae. It is transmitted by a bite or scratch of a kitten or a cat with fleas or occasionally, that of an other pet. Peak transmission is in the early fall or winter. The condition characteristically affects children and adults younger than 21 years. The vast majority of patients can recall a history of cat contact, but not all. Typically, within 2 to 3 days of inoculation, a papule develops and progresses to a vesicle, which is followed by proximal lymphadenopathy in about two weeks. Rarely, the primary lesion at the site of inoculation is pustular or nodular. In fewer than 6% of patients, the primary lesion is followed by a generalized macularpapular and morbilliform eruption.

The involved lymph nodes are tender, often with overlying erythema; occasionally they can suppurate. The lymphadenopathy subsides spontaneously after several months. The diagnosis of cat-scratch disease is primarily clinical.

Differential Dx Cat-Scratch Disease

Cat-Scratch Disease
 Patient has had contact with kittens or cats with fleas  Occurrence is in fall or winter  Primary lesion is a papule or vesicle  Lymph node histopathology is characteristic of the disease

Cutaneous anthrax
 Ulcer and eschar are surrounded by characteristic non-pitting edema  Ulcer with eschar is painless

Chancroid

Chancroid
Chancroid, or soft chancre, is a sexually transmitted disease caused by Haemophilus ducreyi, a gram-negative bacillus. It is relatively uncommon in the United States, but is the most common cause of genital ulcers in Africa. The incubation period is 3 to 7 days. The lesion begins as a soft, red papule. Within 1 to 2 days, it becomes pustular, eroded, and ulcerated. The ulcer is usually 1 to 2 cm in diameter, painful, and covered by a yellowish or gray exudates; it bleeds easily when scraped. The edges of the ulcer are ragged and undermined.

Chancroid does not have a vesicular stage. In males the ulcer is typically located on the distal penis, but may occasionally occur in the urethra and anal orifice. In females, the lesions tend to be localized to the vulva but can also occur in the vaginal, perianal area, and cervix. Painful inguinal lymphadenopathy and over-riding erythema is associated with chancroid in nearly half of all cases in males, less often in female cases. The lymph nodes become fluctuant, can spontaneously rupture, and drain pus. Systemic symptoms can occur but are rare.

Differential Dx Chancroid
Chancroid
 Lesion is located in the anogenital area  Lesion is a painful ulcer without eschar  Lesion lacks vesicular stage

Cutaneous anthrax
 Ulcer and eschar are surrounded by characteristic non-pitting edema  Ulcer with eschar is painless  Lesion is located on exposed parts of the body  Lesion has a vesicular stage

Herpes Simplex

Herpes Simplex
Herpes simplex virus infections are caused by two closely related viruses, identified as type 1 and type 2. They cause a wide variety of primary and recurrent mucocutaneous infections. Following a primary infection, the virus maintains a latent state, and recurrent disease is caused by reactivation of the latent viral infection. Primary genital herpes is the most common cause of genital ulceration. The typical incubation period is 3 to 14 days after sexual exposure. The primary lesion begins as a small group of painful, pruritic vesicles, which break down to form ulcerating, pustular lesions in 2 to 4 days. By the time the patient sees a physician, the lesions are usually in the ulcerative phase. Painful, enlarged inguinal lymph nodes are common. New lesions will continue to form during the first week of the primary illness in about 75% of patients. About two-thirds of patients will have systemic symptoms including fever and headache. Fewer than 10 % of patients will develop aseptic meningitis or urinary retention. The duration of the illness may total 14 to 21 days. In the immunocompromised patient, herpetic infections may be associated with progressive mucocutaneous ulcerations of the face, mouth, or anogenital regions. Lesions may coalesce, forming large, superficial ulcers that last for weeks or months.

Differential Dx Herpes Simplex

Herpes Simplex
 Lesions begin as painful, pruritic grouped vesicles  Vesicles break down to form an ulcer  Lesions are located in the anogenital area

Cutaneous anthrax
 Ulcer is painless  Lesion is located on exposed parts of the body  Ulcer and eschar are surrounded by characteristic non-pitting edema

Lymphogranuloma Venereum

Lymphogranuloma Venereum
Lymphogranuloma venereum (LV) is a sexually transmitted disease caused by chlamydia organisms. LV is found most frequently in the tropical and subtropical parts of the world. The incubation period ranges from 3 to 12 days. The primary lesion is a 5- to 8-mm, soft, red, painless erosion or ulcer. The ulcer heals spontaneously in a few days. The secondary stage begins 2 to 6 weeks later and is characterized by the appearance of tender, inguinal adenopathy, which develops with over-riding erythema and edema. The lymph nodes coalesce, may fluctuate, and drain spontaneously. Associated fever, chills, and malaise can be severe. The late stage of LV is characterized by anogenital strictures in untreated or under-treated cases.

Differential Dx Lymphogranuloma Venereum

Lymphogranuloma Venereum
 Lesion is located in the anogenital area  Genital ulcer or erosion has no eschar  Lymphadenopathy develops after ulcer disappears

Cutaneous anthrax
 Lesion is located on exposed parts of the body  Ulcer and eschar are surrounded by characteristic non-pitting edema  Ulcer and lymphadenopathy are concurrent

Melioidosis
Melioidosis is caused by a gram-negative bacillus, Burkholderia pseudomallei. Infections are endemic in Southeast Asia. The majority of cases are diagnosed in Thailand, Malaysia, Singapore, and northern Australia. Infections are probably acquired as percutaneous inoculations during the wet season from infected soil. Besides living in or traveling to an endemic area, risk factors include diabetes mellitus, alcoholism, and renal failure. Acute disease is defined by symptoms lasting less than 2 months, whereas chronic disease is defined by the presence of symptoms for more than 2 months. Like tuberculosis, melioidosis has the capacity to become latent and be reactivated at a later time. Acute melioidosis can produce suppurative skin infections, pneumonia, or septicemia. Cutaneous lesions are not specific for melioidosis. They may take the form of multiple, superficial pustules or ecthyma gangrenosum. Regional lymphadenopathy is common.

Differential Dx Melioidosis Melioidosis

 Patient resides or has traveled to an endemic area

Cutaneous anthrax
 Ulcer is painless  Lesion is located on exposed parts of the body  Lesion develops a vesicular stage  Ulcer and eschar are surrounded by characteristic non-pitting edema

Cutaneous Nocardiosis
Nocardia species are soil bacteria found worldwide. Disease in humans is rare, and often signals significant immune deficiency. Human infection usually occurs through inhalation, and rarely through direct cutaneous inoculation. In about 50% of cases of inhalational Nocarida bacteria can disseminate particularly to the central nervous system and subcutaneous tissues. The extent of the infection is determined by the immune status of the host. Four clinical types of cutaneous nocardiosis are recognized: mycetoma, lymphocutaneous infection, superficial skin infection, and secondary skin infection associated with disseminated disease. Hematogenous dissemination to the skin, in the form of cellulitis, nodules, or abscesses, probably occurs more often than primary infection of the skin. Primary cutaneous infection may follow skin injury from thorns, insect bites, and even cat scratches. Localized cutaneous infections may present as chronically draining ulcerative lesions, a slowly expanding nodule, or rarely, pustules, abscesses, cellulitis, or pyoderma. In one-third of individuals, the infection can spread to involve the regional lymph nodes, producing a syndrome similar to that of sporotrichosis, known as the lymphocutaneous syndrome. The draining lymphatics become inflamed and swollen and a chain of secondary nodules develops along the course of the lymphatics. These may break down and ulcerate.

Differential Dx Cutaneous Nocardiosis

Cutaneous Nocardiosis
 Pulmonary nodules and skin lesions are present with lymphadenopathy in immunosuppressed patient  Primary lesion is associated with nodular, tender lymphatic chain to regional lymph node

Cutaneous anthrax
 Ulcer with eschar painless  Ulcer and eschar are surrounded by characteristic non-pitting edema

Plague
Plague is caused by Yersinia pestis, a gram-negative bacillus endemic to Arizona, Colorado, California, and New Mexico. Plague is a zoonosis that primarily affects rodents, with humans serving as an "accidental host." Three plague syndromes are recognized: bubonic, septecemic, and pneumonic. Transmission to humans occurs in one of five ways: bite or bites from an infected flea, human-to-human transmission of pneumonic plague, handling of infected animal carcasses, cat bites or scratches, or aerosolization of bacteria. Bubonic plague is the most common human presentation, and fleabites are the most common mode of transmission, followed by contact with infected animals. The initial cutaneous manifestation of bubonic plague appears 2 to 8 days following the fleabite, and can easily be missed. The primary lesion, which consists of a small papule, or vesicopustule, develops at the site of the fleabite. This stage is soon followed by the abrupt onset of fever, chills, headache, weakness, and tender, proximal lymphadenopathy, most commonly occurring in the inguinal areas or axilla. Gastrointestinal symptoms such as nausea, vomiting, and abdominal pain may occur. The involved nodes become enlarged, matted, and associated with extensive overlying erythema and edema (buboes). Bacteremia may follow, resulting in sepsis and death. In the setting of bacteremia, petechiae and ecchymosis develop, and eschars and lesions similar to those of ecthyma gangrenosum may be seen. Eschars and ecthyma gangrenosum-like lesions can also develop at the site of the fleabite in the absence of bacteremia.

Differential Dx Plague Plague

 Patient has traveled to or resides in an endemic site (western United States)  Patient has been exposed to potential rodent or other animal vector  Fever and buboes develop  Signs of bacteremia and DIC (septic form) may be present

Cutaneous anthrax
 Tender lymphadenopathy may be present, but typically buboes are not common  Ulcers are painless  Ulcer and eschar surrounded by characteristic non-pitting edema

Sporotrichosis

Sporotrichosis
Sporotrichosis is an infection caused by Sporothrix schenckii, a fungus that occurs naturally in temperate and tropical locations. Of the two clinical syndromes of sporotrichosis, the subcutaneous and the systemic, the subcutaneous variety is the most common form. The organism is introduced into the skin through a local injury, such as a thorn prick. Subcutaneous sporotrichosis can present as a lymphatic infection or a fixed infection. The lymphatic form is more common and usually develops on exposed skin sites such as the hands or feet. Days to weeks after dermal inoculation, the infection begins as a nodule that may break down to form a small ulcer. The draining lymphatics become inflamed and swollen and a chain of secondary nodules develops along the course of the lymphatics. These may also break down and ulcerate. The nodules are mildly painful, and systemic symptoms are mild or absent. In the fixed variety syndrome, the infection remains localized to the one site. A granuloma develops that may ulcerate. Satellite nodules may form around the primary lesion. This form is most common in tropical and subtropical areas.

Differential Dx Sporotrichosis
Sporotrichosis
 Primary ulcer or nodule is associated with nodular, tender lymphatic chain to draining regional lymph node  Patient may be a gardener or have an outdoor occupation  No vesicular stage

Cutaneous anthrax
 Ulcer with eschar is painless  Ulcer and eschar are surrounded by characteristic non-pitting edema  Lymphatic vessel is not involved

Streptococcal/Staphylococcal Adenitis
Acute lymphangitis is an inflammatory process that involves the superficial lymphatic system. It is most often the result of group A streptococci and can result from Staphylococcus aureus or Pasteurella multocida infections. The portal of entry is usually a wound on the extremity, infected blister, or paronychia. Pain along the lymphatics and regional draining lymph nodes is common as, are systemic symptoms. The diagnosis is suggested by the appearance of red, linear streaks extending from the primary lesion toward the regional lymph nodes, which are enlarged and tender. Rarely, the skin over the primary lesion may break down, forming an ulcer.

Differential Dx
Streptococcal/Staphylococcal Adenitis Streptococcal/Staphylococcal Adenitis
The primary wound is associated with red, linear streaks toward regional lymph node

Cutaneous anthrax
 Ulcer with eschar is painless  Ulcer and eschar are surrounded by characteristic non-pitting edema  Lymphatic vessels are not involved

Tuberculosis
Primary cutaneous inoculation with Mycobacterium tuberculosis or bovis in a previously uninfected host will result in a tuberculosis chancre and regional lymphadenopathy. These findings constitute the primary tuberculosis complex of the skin. Skin lesions develop 2 to 4 weeks after inoculation. The condition is most common where the incidence of tuberculosis is high and hygiene is poor. Most patients are children, but young adults can also be infected, particularly those working in the health professions. The tuberculosis chancre will present as a small papule, scab, or wound that does not heal. A painless ulcer will eventually develop that is quite variable in size, from barely recognizable to as large as 5 cm in diameter. The ulcer is shallow, with a granular or hemorrhagic base, and may be studded with microabscesses, or covered with necrotic debris. The borders are ragged and undermined. As the ulcer ages, the borders become indurated and the ulcer is covered with an adherent crust. Three to 8 weeks following the appearance of the ulcer, a slowly progressive, painless regional lymphadenopathy develops. After several weeks, cold abscesses may perforate the surface of the skin overlying the lymph node to form draining sinuses. More proximal lymph node chains may become involved. In about half of the patients, the course is more acute with fever, pain, and swelling that mimics a typical bacterial infection.

Differential Dx Tuberculosis
Primary tuberculosis complex of the skin
 Patient is a child or health care worker from highly endemic area  Lesion may be slowly progressive  Pustules may be present  Draining sinuses over regional lymph nodes may be present

Cutaneous anthrax
 Lesion progression to ulcerative stage is rapid  Eschar is present  Ulcer and eschar are surrounded by characteristic non-pitting edema  Lymphatic vessels are not involved  Pustules are rare

Tularemia
Tularemia is caused by Francisella tulaeresis, a gram-negative coccobacillus. Six clinical syndromes are recognized: ulceroglandular, glandular, typhoidal, pneumonic, oropharyngeal, and oculoglandular. As many as 80% of the cases are ulceroglandular, and are the result of direct contact with infected animals; the organisms are introduced through minor skin abrasions. They can also be caused by the bite of an animal, espically a cat, or an insect vector, particularly a tick or deer fly. After an incubation period of 2 to 10 days, there is an abrupt onset of fever, chills, headache, and myalgias. The primary lesion develops at the site of inoculation, usually the hand, is associated with regional lymphadenopathy, and occasionally, nodular lymphangitis. The primary lesion begins as a single, red, painful papule that develops a central ulcer with raised margins, often covered by a black eschar. Systemic toxicity can be marked.

Differential Dx Tularemia
Tularemia
 Onset follows contact with cats, rabbits, foxes, squirrels, muskrats, beavers, and pheasants or potential exposure to tick or deer fly vector  Lesion is a painful papule or ulcer

Cutaneous anthrax
 Ulcer is painless  Ulcer and eschar are surrounded by characteristic non-pitting edema

Antiphospholipid Antibody Syndrome Ulcers

Antiphospholipid Antibody Syndrome Ulcers

Antiphospholipid antibodies (APLAs) constitute a large family of autoantibodies, including lupus anticoagulants and anticardiolipin antibodies. These antibodies may occur in several clinical contexts. First, APLAs are present in 2% to 5% of healthy blood donors, and their prevalence is increased dramatically in the elderly. Second, APLAs are common in persons with autoimmune disorders; for example, they are found in as many as 60% of patients with systemic lupus erythematosus. Third, APLAs may develop in persons exposed to medications such as procainamide, quinidine, and chlorpromazine. Fourth, APLAs are found frequently in patients with HIV infection or in patients with congenital immunodeficiency syndromes. APLAs may also be present transiently in as many as 30% of children following common viral infections. Several studies have suggested a genetic predisposition to the development of these antibodies.

An association of APLAs with thrombosis and recurrent fetal loss is well supported. In patients with APLAs, thrombosis can be either venous or arterial; the former type is slightly more common. Venous thrombi usually develop in high-risk contexts, such as during pregnancy, after surgery, or in association with prolonged immobilization. Arterial thrombi may involve any central or peripheral vessel. APLAs have been associated with a number of cutaneous disorders including livido reticularis, livido vasculitis, cutaneous necrosis, infarctions and ulceration, subungual splinter hemorrhages, and vasculitis (palpable purpura).

Differential Dx Antiphospholipid Antibody Syndrome Ulcers

Antiphospholipid Antibody Syndrome Ulcers
 Symptoms occur in appropriate clinical context (elderly, patients with autoimmune disorders, exposure to procainamide, quinidine, and chlorpromazine)  Patients may have other manifestations including arterial or venous thrombosis  Ulcers are painful  Laboratory evidence reveals prolonged prothrombin time

Cutaneous anthrax
 Ulcer is painless  Ulcer and eschar surrounded by characteristic non-pitting edema  There is no evidence of other thrombotic conditions

Aspergillosis and Mucormycosis

Systemic Mycoses
Aspergillus, a systemic mycosis, produces cutaneous ulcers most often by direct implantation following trauma, and much less commonly, following dissemination from a primary pulmonary tract infection. The lesion begins as a papule, evolving into an ulcer. The rate and extent of ulcer enlargement depend largely upon the degree of immunosuppresion. Patients with large, rapidly progressive ulcers typically have severe underlying disease states, such as AIDS, neutropenia, or functional neutrophil defects. These ulcers can take on the appearance of ecthyma gangrenosum. Zygomycetes (mucormycosis) is a class of fungi capable of causing a variety of systemic infections in humans. Cutaneous infections are usually the result of direct inoculation into the skin and are almost always associated with trauma or wounds. In some cases, the trauma may seem trivial, such as an intravenous catheter insertion or insulin injection site. Patients with mucormycosis typically have serious, underlying immune disorders or challenges, such as diabetes mellitus, organ transplantation, or neutropenia. Infection in these hosts typically begins as a single, painful, indurated area of cellulitis, progressing to ulceration. It may take on the appearance of ecthyma gangrenosum. Infection can also occur in large traumatic wounds or burns, when associated with contaminated dressings or splints. In such cases, the infection appears as an ischemic tissue infarction.

Differential Dx Aspergillosis and Mucormycosis

Mucotic Infections
 Lesion is localized in a prior burn site, wound, or injury, possibly trivial  Patient has AIDS, severe neutropenia, or functional neutrophil defects  Patient has poorly controlled diabetes, neutropenia, or renal disease  Infection is associated with contaminated dressing or splints  Ulcers are painful

Cutaneous anthrax
 Patient has no underlying immune deficiency  Ulcer is painless  Ulcer and eschar are surrounded by characteristic non-pitting edema

Brown Recluse Spider Bite

Brown Recluse Spider Bite

The brown recluse spider, Loxosceles reclusa, is widely distributed in the United States throughout the Southeast and Midwest. Its natural habitat is outdoors under overhanging rocks and cliffs; it also lives in closets, attics, and outbuildings. The brown recluse hibernates during the winter; most bites occur between March and October. Responses to bites range from mild local urticarial (hive-like) reactions to full-thickness skin necrosis. The more extensive reactions may be associated with systemic manifestations including a maculopapular rash, fever, headache, malaise, joint aches, and nausea and vomiting. The bite itself is generally painless, and the findings of a central papule and associated redness may not be seen for 6 to 12 hours. Only approximately 10% of bites progress to skin necrosis; those that do tend to show progression in 48 to 72 hours. Central blistering with a surrounding gray to purple discoloration at the bite site may appear. The site is surrounded by a ring of blanched skin that in turn is surrounded by a large area of redness, producing the "red, white, and blue" sign typical of a brown recluse spider bite. At this stage, the bite is associated with significant pain. As the wound becomes necrotic, it will turn black. Healing is slow and may require skin grafting to cover the defect. Not all victims recall the spider bite, and because the clinical appearance is nonspecific, diagnosis can be difficult.

Differential Dx Brown Recluse Spider Bite

Brown Recluse Spider Bite
 Patient has a possible history of spider bite or recent exposure to spider habitat  Bite lesion becomes painful  Lesion may manifest the red, white and blue sign

Cutaneous anthrax
 Ulcer with eschar is painless  Ulcer and eschar are surrounded by characteristic non-pitting edema

Coumarin and Heparin Necrosis

Coumarin and Heparin Necrosis

Cutaneous ulcers are a rare complication of coumarin therapy. In most cases, symptoms begin 3 to 5 days after initiation of coumarin; the most common areas of involvement are the thighs, breasts, and buttocks. The lesions can be single or multiple. They present with localized pain, followed by the development of erythema, progressing to blue-black lesions that may blister. A painful, necrotic eschar develops at the site of the blister. Most patients with coumarin necrosis have low levels of protein C, a serine protease that has anticoagulant and fibrinolytic activity. In the presence of coumarin, levels of protein C fall more rapidly than do procoagulant factors IX, X and prothrombin. Therefore, when coumarin is given to a patient with low levels of protein C, a transient hypercoagulable state can develop causing local thrombosis of dermal vessels. Coumarin necrosis is most likely to occur in patients in whom large initial doses of coumarin (greater than 10 mg) have been initiated in the absence of heparin anticoagulation.

Coumarin and Heparin Necrosis (cont)

A clinically similar reaction can occur with heparin. Patients with heparin necrosis, however, do not have deficiencies in natural anticoagulants. They do develop heparin-induced platelet antibodies, but without associated thrombocytopenia. Patients being given heparin can develop heparin-induced thrombocytopenia, or HIT. Symptoms occur after 5 to 15 days of heparin exposure, although pre-sensitized persons may experience HIT within hours of rechallenge. This disorder develops in 1% to 3% of patients who are treated with standard intravenous doses of unfractionated heparin, but can occur in patients who receive heparin by any route, or at any dose, including heparin flushes. Platelet counts are usually in the range of 20,000 to 100,000/L. Arterial and venous thrombosis develops in approximately 30% of patients with HIT. This syndrome, referred to as heparin-induced thrombocytopenia with thrombosis syndrome (HITTS), occurs most often in patients who have additional risk factors, such as postoperative immobilization. Patients with extensive venous thrombosis may develop venous limb gangrene and secondary skin ulceration.

Differential Dx Coumarin and Heparin Necrosis

Coumarin and Heparin Necrosis

 Patient has recently begun on coumarin or heparin  Patients with HITTS have additional thrombotic manifestations  Ulcers are painful

Cutaneous anthrax
 Patient is not on heparin or coumarin  Ulcer is painless  Ulcer and eschar are surrounded by characteristic non-pitting edema

Ecthyma and Ecthyma Gangrenosum

Ecthyma and Ecthyma Gangrenosum

Ecthyma is a condition in which the exudate or crust of a pyogenic infection involves the entire epidermis. The crust can be thick and adherent. Ecthyma is usually the consequence of neglected impetigo caused by Staphylococcus aureus or group A streptococcus. Ecthymatous lesions can evolve from localized skin abscesses (boils) or within sites of preexisting trauma. The margin of the ecthyma ulcer can be indurated, raised, and violaceous. Untreated ecthymatous lesions can enlarge over the course of weeks or months to a diameter of 2 to 3 cm. Staphylococcal and streptococcal ecthyma occur most commonly on the lower extremities of children, the elderly, and people who have diabetes. Poor hygiene and neglect are key elements in its pathogenesis. Ecthyma gangrenosum is characterized by single or multiple, cutaneous or mucous membrane ulcers that are most often associated with prolonged neutropenia, Pseudomonas aeruginosa bacteremia, and other serious bacterial infections. Ecthyma gangrenosum resembles ecthyma caused by staphylococcal or streptococcal organisms. First presenting as a painless nodular lesion, it quickly develops a central hemorrhagic area that subsequently breaks down to form a large necrotic ulcer.

Differential Dx Ecthyma and Ecthyma Gangrenosum

Ecthyma
 Lesions are located most commonly on lower extremities  Systemic symptoms are unusual  Lesion progresses slowly

Cutaneous anthrax
 Lesion is located most commonly on upper extremities (especially the hands), neck, or face  Systemic manifestations include fever, malaise, regional lymphadenopathy  Ulcer and eschar are surrounded by characteristic non-pitting edema

Differential Dx Ecthyma and Ecthyma Gangrenosum

Ecthyma Gangrenosum
 Lesion is associated with neutropenia  Lesion may be associated with Pseudomonas bacteremia  Multiple lesions may occur

Cutaneous anthrax
 Ulcer and eschar are surrounded by characteristic non-pitting edema

Factitious Ulcer

Factitious Ulcer
Factitious ulcers are self-induced lesions. They can be single or multiple, and are typically located on part of the body within easy reach of the dominant hand. The ulcer morphology is often angulated or geometric with patterns of necrosis that do not resemble any known dermatosis. The condition is most common in adolescents and young adults, but can occur at any age. Adult patients with factitious ulcers have personalities that are infantile, dependent, and manipulative, with poor impulse control. Many patients are health care workers or have family members who are health care workers. The patient is characteristically not distressed by the lesions, which appear not to be painful. Patients will deny responsibility for the lesions. The diagnosis is based upon the bizarre morphology of the lesion, and personality of the patient.

Differential Dx Factitious Ulcer

Factitious Ulcer
 Shape of the lesion is bizarre  Lesion is within reach of dominant hand  Personality of the patient is infantile, dependent

Cutaneous anthrax
 Ulcer and eschar are surrounded by characteristic non-pitting edema  Typical lesion progresses from papule, vesicle, or bulla, to formation of edema, necrotic ulcer, and eschar

Orf/Milkers Nodule

Orf/Milkers Nodule
Orf virus is a member of the Poxviridae family. It produces disease mainly among sheep, goats, and musk oxen, but can occasionally be transmitted to humans. Farmers and veterinarians are among the most likely to be exposed to the virus. The orf lesion is approximately 1.5 cm in diameter, and is usually a solitary lesion located on the dorsal aspect of the finger. Regional lymphadenopathy, lymphangitis, and fever are common symptoms. The disease passes through several distinct stages: 1) 2) 3) 4) The lesion begins as a red, solid, elevated papule. Next, it enlarges into a nodule with a red center, white middle ring, and red periphery (the target stage). In the acute stage, a red weeping surface is present. In the regenerative stage, a thin, dry crust develops, through which black dots may be seen covering the surface of the nodule. In the next stage, small papillomas, or tiny growths, cover the surface. Finally, during the regressive phase, a thick crust develops over the surface of the lesion, papillomas decrease in size, and the lesion flattens out.

5) 6)

Differential Dx Orf/Milkers Nodule

Orf Lesion
 Lesion is found primarily on the dorsal fingers of farmers and veterinarians  Patient has had contact with sheep, goats, and musk oxen  Lesion is associated with crusts and scabbing

Cutaneous anthrax
 Lesion is not limited to fingers  Ulcer and eschar are surrounded by characteristic non-pitting edema

Rickettsialpox, Scrub Typhus, and Tick Typhus

Rickettsialpox is an uncommon condition caused by Rickettsia akari, transmitted to humans by the mouse mite. Cases have been described primarily in New York City, Pittsburgh, Cleveland, and Boston and in Arizona and Utah. One to two days following the mite bite, a red papule forms at the site of inoculation, and enlarges to 1 to 1.5 cm. A vesicle then forms in the center of the papule, producing a red halo. The vesicles dries, and a black eschar forms, followed by the abrupt onset of fever and proximal lymphadenopathy. The fever lasts about a week and is associated with a generalized macular-papular-vesicular eruption, often mimicking chickenpox. The rash is sparse, usually located on the face, trunk, and extremities, but may involve the palms, soles, and oral mucosa.

Rickettsialpox, Scrub Typhus, and Tick Typhus (continued)

Scrub typhus, caused by Orientia tsutsugamushi, is transmitted by the bite of a larval mite, also known as a "chigger". It produces disease in India, Southeast Asia, and Australia. A red papule forms, followed by a vesicle or black eschar on the papular base. Systemic symptoms include fever, chills, and headache. On the fifth day of fever, a generalized macular and papular, or occasionally papularvesicular rash develops on the abdomen, progressing to the extremities. This stage of the illness is frequently associated with generalized lymphadenopathy. Tick typhus can be produced by a number of different but closely related rickettsiae found in the eastern hemisphere. Five to 7 days following inoculation, the illness begins suddenly with fever and headache. The primary lesion begins as a red papule, which ulcerates and is then covered by an eschar, surrounded by a red halo. The primary lesion associated with regional and then generalized lymphadenopathy. After about four days of fever, a generalized, red, macular and papular rash develops.

Differential Dx
Rickettsialpox, Scrub Typhus, and Tick Typhus Rickettsialpox, Scrub Typhus, and Tick Typhus
 Disease is associated with a generalized macular-papular or papular-vesicular rash  Papular base is discernible under the vesicle or eschar  Patient resides in or has traveled to endemic areas (scrub typhus and tick typhus)

Cutaneous anthrax
 Ulcer and eschar are surrounded by characteristic non-pitting edema  No other cutaneous manifestations are present

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