Rocky Mountain spotted fever differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Michael Maddaleni, B.S.; João André Alves Silva, M.D. [2]; Ilan Dock, B.S.


Rocky Mountain spotted fever (RMSF) must be differentiated from other diseases that cause fever, headaches, muscle pain, and rash. In virtually all cases, RMSF presents with a rash. When trying to differentiate RMSF from other infections, it should be noted that there has been a rare case in which RMSF has presented itself without the typical rash. Examples of misdiagnosed, rickettsiae caused, diseases include typhus-spotted fevers and Ehrlichiosis. Other misdiagnoses include pox diseases and acne.When diagnosing Rocky Mountain spotted fever it's important to account for patient history such as exposure to endemic regions and a history of tick bites. Although immunofluorescence assays, polymerase chain reactions, and immuno-staining remain the most effective ways of determining a RMSF infection.

Differential Diagnosis

Examples of diseases that may be misdiagnosed for Rocky Mountain spotted fever are found in the table below:

Disease Symptoms
Common Typhus Infections (Rickettsia)
Rocky Mountain Spotted Fever Fever, alterations in mental state, myalgia, rash, and headaches.
Helvetica Spotted Fever [1] Rash: spotted, red dots. Respiratory symptoms (dyspnea, cough), muscle pain, and headaches.
Ehrlichiosis Anaplasmosis [2] Fever, headache, chills, malaise, muscle pain, nausea, confusion, conjunctivitis, or rash (60% in children and 30% in adults).
Other Diseases with Clinical Manifestations Similar to RMSF[3]
Insect bites In an insect bite, the insect injects formic acid, which can cause an immediate skin reaction often resulting in a rash and swelling in the injured area, often with formation of vesicles.
Kawasaki disease Symptoms include high and persistent fever, red mucous membranes in mouth, "strawberry tongue", swollen lymph nodes and skin rash in early disease, with peeling of the skin on the hands, feet and genital area.
Measles Symptoms include high fever, coryza and conjunctivitis, with observation of oral mucosal lesions (Koplik's spots), followed by widespread skin rash.
Monkeypox Clinical presentation is similar to smallpox, although it is often a milder form, with fever, headache, myalgia, back pain, swollen lymph nodes, a general feeling of discomfort, and exhaustion. Within 1 to 3 days (sometimes longer) after the appearance of fever, the patient develops a papular rash, often first on the face. The lesions usually develops through several stages before crusting and falling off.
Rubella Symptoms include a facial rash which then spreads to the trunk and limbs, fading after 3 days, low grade fever, swollen glands, joint pains, headache and conjunctivitis. The rash disappears after a few days with no staining or peeling of the skin. Forchheimer's sign occurs in 20% of cases, and is characterized by small, red papules on the area of the soft palate.
Atypical measles Symptoms commonly begin about 7-14 days after infection and clinically present as fever, cough, coryza and conjunctivitis. Observation of Koplik's spots is also a characteristic finding in measles.
Coxsackievirus The most commonly caused disease is the Coxsackie A disease, presenting itself as hand, foot and mouth disease. It may be asymptomatic or cause mild symptoms, or it may produce fever and painful blisters in the mouth (herpangina), on the palms and fingers of the hand, or on the soles of the feet. There can also be blisters in the throat or above the tonsils. Adults can also be affected. The rash, which can appear several days after high temperature and painful sore throat, can be itchy and painful, especially on the hands/fingers and bottom of feet.
Acne Typical within teenage populations, usually appears on the face and upper neck, but the chest, back and shoulders may have acne as well. The upper arms can also have acne, but lesions found there are often keratosis pilaris, not acne. The typical acne lesions are comedones and inflammatory papules, pustules, and nodules. Some of the large nodules were previously called "cysts."
Syphilis Generalized systemic symptoms such as malaise, fatigue, headache and fever. Skin eruptions may be subtle and asymptomatic. It is classically described as 1) non-pruritic bilateral symmetrical mucocutaneous rash; 2) non-tender regional lymphadenopathy; 3) condylomata lata; and 4) patchy alopecia.
Molluscum contagiosum Lesions are commonly flesh-colored, dome-shaped, and pearly in appearance. They are often 1-5 millimeters in diameter, with a dimpled center. Generally not painful, but they may itch or become irritated. Picking or scratching the lesions may lead to further infection or scarring. In about 10% of the cases, eczema develops around the lesions. They may occasionally be complicated by secondary bacterial infections.
Mononucleosis Common symptoms include low-grade fever without chills, sore throat, white patches on tonsils and back of the throat, muscle weakness and sometime extreme fatigue, tender lymphadenopathy, petechial hemorrhage and skin rash.
Toxic erythema Common rash in infants, with clustered and vesicular appearance.
Rat-bite fever Symptoms include fever, chills, open sore at the site of the bite and rash, which may show red or purple plaques.
Parvovirus B19 Typically described as "slapped cheeks," with erythema across the cheeks and sparing the nasolabial folds, forehead, and mouth.
Cytomegalovirus Symptoms include sore throat, swollen lymph nodes, fever, headache, fatigue, weakness, muscle pain and loss of appetite.
Scarlet fever Symptoms include fever, punctate red macules on the hard and soft palate and uvula (Forchheimer's spots), bright red tongue with a "strawberry" appearance, sore throat and headache and lymphadenopathy.
Stevens-Johnson syndrome Symptoms may include fever, sore throat and fatigue. Commonly presents ulcers and other lesions in the mucous membranes, almost always in the mouth and lips but also in the genital and anal regions. Those in the mouth are usually extremely painful and reduce the patient's ability to eat or drink. Conjunctivitis of the eyes occurs in about 30% of children. A rash of round lesions about an inch across, may arise on the face, trunk, arms and legs, and soles of the feet, but usually not on the scalp.
Varicella-zoster virus Commonly starts as a painful rash on one side of the face or body. The rash forms blisters that typically scab over in 7-10 days and clears up within 2-4 weeks.
Chickenpox Commonly starts with conjunctival and catarrhal symptoms and then characteristic spots appearing in two or three waves, mainly on the body and head, rather than the hands, becoming itchy raw pox (small open sores which heal mostly without scarring). Touching the fluid from a chickenpox blister can also spread the disease.
Meningococcemia Symptoms include rash, petechiae, headache, confusion, and stiff neck, high fever, mental status changes, nausea and vomiting.
Rickettsialpox Initial symptom is commonly a bump formed by a mite-bite, eventually resulting in a black, crusty scab. Many of the symptoms are flu-like including fever, chills, weakness and muscle pain but the most distinctive symptom is the rash that breaks out, spanning the person's entire body.
Meningitis Symptoms include headache, nuchal rigidity, fever, petechiae and altered mental status.
Impetigo Symptoms include pimple-like lesions surrounded by erythematous skin. Lesions are pustules, filled with pus, which then break down over 4-6 days and form a thick crust. It's often associated with insect bites, cuts, and other forms of trauma to the skin.


  1. Rocky Mountain Spotted Fever Information. Centers for Disease Control and Prevention (2015). Accessed on December 30, 2015
  2. Disease index General Information (2015). Accessed on December 30, 2015
  3. Moore, Zack S; Seward, Jane F; Lane, J Michael (2006). "Smallpox". The Lancet. 367 (9508): 425–435. doi:10.1016/S0140-6736(06)68143-9. ISSN 0140-6736.