Rocky Mountain spotted fever (RMSF) typically presents as a triad with fever, rash, and headache. It presents dermatologically as a maculopapular rash on the hands and feet along with a late petechial rash on the forearm and hands. The exanthema consists of small blanching pink macules, located in the arches, wrists, and forearms, eventually expanding to the proximal extremities and torso.¹,²,³

This disease has its greatest incidence during the late spring and early summer months, when ticks are most active and act as arthropod vectors for the organism Rickettsia rickettsii. Usually 1 week following a tick bite, RMSF presents with an abrupt onset characterized by severe headache, fever, chills, nausea, and generalized myalgia. The fourth febrile day is joined by the onset of erythematous macules that start on the hands and feet and then spread centrally to the trunk and face. Two to three days later, the macules become papular and then purpuric, consistent with vasculitis. These same changes occur within viscera, potentially resulting in shock or renal failure.

The diagnostic tools used to confirm RMSF are serologic testing and skin biopsy. The best serologic test is immunofluorescent antibody assays. Also available are enzyme-linked immunosorbent assays and latex agglutination assays. If RMSF is suspected, treatment should not be delayed while
awaiting confirmatory test results. The drug of choice used to treat RMSF is doxycycline. It is a broad spectrum antibiotic, in the tetracycline family. When doxycycline is administered for short courses and under strict guidelines, it has not been found to discolor teeth in children <8 years old; however, use in pediatric patients is usually the contraindication.

Although presenting in a fashion similar to RMSF, the rash of meningococcemia occurs very rapidly after the onset of constitutional changes. In addition, nuchal rigidity and pain on passive flexion of the neck (secondary to stretching of painful meninges) provide additional differentiating clues.

The widespread ecchymosis and limb ischemia is usually preceded by a petechial or purpuric rash that is rapidly spreading.⁴ The process involves a number of factors that are initiated by a bacterial infection invading the soft tissue, causing swelling, hypoperfusion, and hypoxia, ultimately resulting in disseminated intravascular coagulation.⁵

It is recommended to have blood cultures drawn prior to the start of treatment, and if the patient is stable, a lumbar puncture is also recommended. Having said that, therapy should not be delayed if the suspicion is high and the diagnostic procedures are not performed.⁵

The following are the current treatment options⁵: ceftriaxone 100 mg/kg/d in one to two divided doses, cefotaxime 200 mg/kg/d in three divided doses, and penicillin G 500,000 units/kg/d in six divided doses.

Prophylaxis against meningococcus is recommended for those who have been in close contact with the patient. In this case, the drug of choice is rifampin, which is administered every 12 hours for 2 days or, alternatively, a single dose of ciprofloxacin or ceftriaxone.⁵

Patients who present with a chronic meningococcemia pose a diagnostic challenge. They usually present with prolonged periods of intermittent fever, arthritis that is migratory, as well as disseminated skin lesions in the form of macules or nodules that are erythematous.⁶ Patients with chronic meningococcemia may fail to reveal its identity with routine microbiologic testing. It has been suggested in these cases that polymerase chain reaction (PCR) testing of the skin biopsy be performed along with an immunohistochemical approach, sometimes using silver staining of the lesions.⁶

The ham-colored maculopapular rash of secondary syphilis usually presents within 3 to 6 weeks after the appearance of the primary chancre. The rash is always painless, and never hemorrhagic or vesiculobullous. Plaques, nodules, and ulcerated lesions are rare but can also occur. Lesions develop slowly in crops rather than abruptly. Constitutional symptoms are absent. The reader is reminded that guttate palmoplantar keratoses also exist in this stage.

Diagnostic procedures may include HIV, hepatitis B/C, Venereal Disease Research Laboratory (VDRL), Treponema pallidum particle agglutination test, and anti-T. pallidum immunoglobulin M enzyme-linked immunosorbent assay (ELISA) index.⁷,⁸ The serologic tests are also combined with immunohistochemical staining of the lesional and nonlesional skin using PCR and Ziehl-Neelsen stain.⁷

The treatment involves giving the patient a prophylactic dose of prednisone to avoid a Jarisch-Herxheimer reaction. Then treatment would follow with weekly injections of 2.4 million units of benzathine penicillin (PCN) for three consecutive weeks. It can also be dosed at 1 million units for 21 days, depending on the specific guidelines being followed.⁸

Often considered a familial form of amyloidosis with childhood onset, familial Mediterranean fever (FMF) presents with hot, tender, erythematous patches on the calves, ankles, or the dorsa of the feet. FMF is a condition that results in recurrent episodes of fever and polyserositis, which does not involve infection or autoantibodies.⁹,¹⁰ It is an autoinflammatory condition that results from a mutation in the MEFV gene, which usually starts during childhood.⁹,¹⁰ Laboratory tests may include elevations in serum amyloid A, erythrocyte sedimentation rate, C-reactive protein, leukocytosis, and fibrinogen during febrile episodes. Definitive diagnosis is made with genetic testing and confirmed when a mutation of the MEFV gene is established.¹ The mainstay of treatment is colchicine, but in cases where there are patients resistant to the drug, interferon-α may be a treatment option.⁹,¹⁰

Kawasaki disease is a condition that typically affects infants and young children. It is known as a self-limiting disease causing systemic vasculitis, resulting in coronary artery aneurysms, myocardial infarctions, and death if not promptly diagnosed and treated.¹¹ The diagnosis is based on both clinical and laboratory findings. The following is required to make the diagnosis, persistent fever >101°F for a minimum of 5 days along with at least four of the following characteristics: edema and erythema of the extremities; bilateral bulbar conjunctival injection without exudate; edema of the oropharynx with lips that become cracked or red, a “strawberry tongue”; erythematous rash; and cervical lymphadenopathy.¹¹ This disease demonstrates palmoplantar erythema and pedal edema, followed by a course of marked desquamation of the palms and soles. These patients often have fevers that continue to spike despite being treated with antipyretics and antibiotics. The diagnosis may also be made if fever is persistent for a minimum of 5 days, and less than four of the respective criteria are met, if there are coronary abnormalities found on 2D echo, or if four or more of the critical criteria have been established.¹² The drug of choice for Kawasaki disease is intravenous immunoglobulin and acetylsalicylic acid (aspirin) (ASA); steroids and immunosuppressive therapy may also be a treatment option for those patients who fail to respond to the initial therapy.¹¹

In addition to palmoplantar erythema and onycholysis, patients may present with a combination of diffuse goiter, exophthalmos, pretibial myxedema, nail clubbing, and periosteal new bone formation (the combination is often referred to as “thyroid acropachy”).

In this disorder, an α-cell tumor of the pancreas results in increased serum glucagon levels coupled with erythematous macules and patches that transform into flaccid bullae (Fig. 15-1). The blisters subsequently rupture to leave a collarette of desquamating skin. Lesions have a predilection for the abdomen, groin, thighs, hands, periorificial areas, legs, and feet. Although the dermatosis responds to oral diiodohydroxyquin, removal of the tumor leads to resolution of the skin changes.

The lesions may begin as erythematous macules and therefore are included for the sake of completeness. They rapidly progress to purpuric macules and papules; a more complete discussion may be found in the section on purpuric lesions.

Brown macules may be found on the palms, soles, and mouth (lips) (Fig. 15-2). These outward signs are associated with gastrointestinal polyposis. Historically, treatment options involved cryotherapy, surgical removal, dermabrasion, electric cautery, and the use of carbon dioxide and argon lasers.¹³ Alternatively, Li et al.¹³ have studied the use of a Q-switched alexandrite laser in the treatment of both labial and facial lentigines associated with Peutz-Jeghers syndrome. Their results revealed that after three treatments, 55.8% (24/43) of their patients had excellent results and 44% (19/43) had good results.¹³ They did not document any serious complications related to the use of the laser.

Although more fully discussed in other chapters of this text, Kaposi sarcoma (KS) is included because it may present with violaceous macules and papules that coalesce (Fig. 15-3). Four types of KS are generally recognized: classic, African, allograft associated, and epidemic (AIDS related). It is imperative that AIDS-associated KS be treated with highly active antiretroviral therapy.¹⁴ Other treatments include intralesional chemotherapy or radiation therapy, with systemic chemotherapy reserved for advanced cases of the disease and AIDS-associated KS.¹⁴

Patients with KS secondary to the classic type may do well using laser and photodynamic therapy.¹³ It has also been shown that the classic type as well as patients who
are elderly and immunocompromised have responded well to the use of topical immune response modifiers.¹⁵ The use of intralesional 3% sodium tetradecyl sulfate has also been proposed, especially in cases where KS presents as nodular lesions, ultimately resulting is sclerotization of the vessels.¹⁵

Patients present with diffuse keratoses of their palms and soles bilaterally, in association with a past or present history of esophageal carcinoma. At times, suspecting clinicians may first make the diagnosis solely on the basis of diffuse palmoplantar keratoses in a patient with symptoms of dysphagia and/or hematemesis.

Diffuse plantar keratoses, thick and brittle nails, and easy bruisability of the legs (manifested as purpura or ecchymoses) suggest the diagnosis. Confirmation is aided by finding the cardinal symptoms and signs of weight gain, constipation, cold intolerance, and mental or physical sluggishness. The hypothyroid foot can closely resemble one with the dry, scaly form of tinea pedis. This diagnosis might therefore be considered in patients who are unresponsive to standard antifungal therapy.

Acute intoxication does not fall into this category because it presents with nausea, vomiting, and other signs of gastrointestinal upset rather than skin change. Ingestion of contaminated groundwater is considered to be the most common cause of chronic arsenic poisoning, especially endemic in regions such as Bangladesh, Inner Mongolia, China, and the West Bengal province of India.¹⁶,¹⁷,¹⁸ Inorganic arsenic sulfide was also found in Chinese proprietary medicines as well as in American tobacco in the 1950s.¹⁹ There appears to be a dose-response relationship or rather a dose and frequency relationship, with skin manifestations being the most common adverse effect; furthermore, chronic exposure has been known to increase the risk of cancer affecting multiple organs and not limited to the skin.¹⁶,¹⁷,¹⁸ The most common initial skin manifestations are melanosis, keratosis, leukomelanosis, and hyperkeratosis¹⁶,¹⁷,¹⁸ (Fig. 15-4). There are a number of treatment options for the skin manifestations secondary to chronic arsenic exposure; however, the effects may be irreversible, though worth exploring, and may involve phototherapy, topical keratolytics, and chemotherapeutic agents along with surgical excision and cryotherapy.¹⁷

Guttate keratoses of the palms and soles are also found in patients with secondary syphilis. Concomitantly, they also exhibit a generalized, ham-colored, maculopapular rash (Fig. 15-5). Questions should be posed regarding sexual history, and the spontaneous resolution of a genital “sore” (the primary chancre).