Synonyms: None
Etiology: Rickettsia rickettsii following Dermacentor sp. tick bite
Associations: Outdoor recreational activity
Clinical: Fever/headache followed by macules and petechial eruption of wrists/ankles with subsequent generalization
Histology: Lymphocytic vasculitis with vascular thrombosis, epidermal necrosis organisms with special stains seen in vascular wall
IHC repertoire: Organisms identified by immunohistochemical and immunofluorescent antibodies
Staging: Not applicable
Prognosis: Fatality rate of 20% –30%, worse in the elderly or with coexisting G6PD deficiency
Adverse variables: Renal failure, myocarditis, arrythmias, DIC and ARDS
Treatment: Intravenous tetracycline, doxycycline, or chloramphenicol
26
Rocky Mountain Spotted Fever and the Rickettsioses
The rickettsioses constitute a diverse group of arthropod- borne human diseases capable of producing significant morbidity and mortality. They share important patho- logic and clinical attributes that permit their diagnosis in most instances (1). The rickettsioses are responsible for a great number of deaths seen particularly in times of war.
It is estimated that over 3 million combatants and civil- ians in the First World War succumbed to epidemic typhus. Among the more deadly types of infection belong- ing to this group is Rocky Mountain Spotted Fever, the principal subject of this chapter.
The rickettsioses are endemic to most areas of the world where contact with arthropods, namely biting ticks, mites, fleas, and lice, can be found. They can be broadly catego- rized into tick-borne agents that principally include Rocky Mountain Spotted Fever (R. rickettsii) and Meditteranean fevers (R. conorii), mite-borne diseases including rickett- sialpox (R. akari) and scrub typhus (Orientia tsutsugamu- shi, formerly R. tsutsugamushi), flea-borne endemic typhus (R. typhi), and louse-borne epidemic thyphus (R. prowaze- kii). Q fever is unique within the group as its etiologic agent Coxiella burnetti is acquired following aerosolization of infected tissues. They can also be subcategorized into the spotted fever group or the typhus group on the basis
of shared immunologic or biologic properties (2). The infectious agents are among the smallest of bacteria at 0.3–10−6mm. They are considered to be gram-negative and exist as pleomorphic-appearing bodies either exclusive to the cytoplasm of infected cells (typhus group) or the nucleus and cytoplasm (spotted fever group). They require passage via blood-consuming arthropod vectors that use infected mammals and the arthropods themselves as a reservoir. Once introduced into the skin, the organisms attach to endothelial cell membranes until phagocytosed by inflammatory cells with subsequent hematogenous or lymphatic passage throughout the body.
Rocky Mountain spotted fever (RMSF) was first described in the late nineteenth century among settlers in the still-wild frontier of the American West, hence the term “Rocky Mountain” fever. RMSF is the most common rickettsial infection reported in North America and though found throughout the continent, is most common in the south Atlantic region of the United States (3). The most important vector for disease is the dog tick or Der- macentor variabilis and the Rocky Mountain wood tick Dermacentor andersonii. The etiologic agent R. rickettsii is transmitted with blood-meals of the infecting ticks, which usually requires at least a 6-hour interval of feeding (4).
125
126 Deadly Dermatologic Diseases
Most infections occur during the summer and are most commonly seen in children or adult males engaged in outdoor recreational activity. Insect repellants, protective outer garments, periodic tick surveillance, and timely and efficacious extraction of feeding ticks are all important means of disease prevention (5).
The clinical manifestations are ushered in by high fever, chills, myalgia, and headache at an average of 7 days fol- lowing exposure (range 2–14 days). The fever often exceeds 102 degrees and may be accompanied by gastrointestinal complaints (6). The cutaneous manifestation, namely rash, follows within 2 to 4 days after the initial complaints and consists of a macular followed by papular petechial rash (Figure 26.1). The rash initially begins on the wrists and or ankles and spreads to the trunk over the ensuing day. Palm and or sole involvement is fairly uncommon, yet can occur. The classic triad of fever, headache, and rash is present in about 60% of patients. A distinct minority (∼10%) of patients may never develop rash, so-called spot- less fever. This is most commonly seen in the elderly or among the dark-skinned races. The rash is most often accompanied by systemic manifestations including hypo- volemia, tachycardia, and peripheral edema. Important complications include epidermal necrosis in conjunction with ischemic vascular thrombosis with digital or extrem- ity loss, scarring, and visceral organ failure including hepatic or renal failure, cardiomyopathy with electrical instability, disseminated intravascular coagulation, the adult respiratory distress syndrome, and CNS involve- ment with delirium or seizure. Motor deficits, cranial nerve palsy, or coma may also be seen.
Important laboratory abnormalities routinely encoun- tered in these patients include thrombocytopenia and normochromic normocytic anemia with increased pro- thrombin times and decreased fibrinogen, hyponatremia, hepatic transaminasemia with hyperbilirubinemia, and elevated BUN and creatinine levels.
Biopsies from the skin rash show perivascular lymp- hocytic infiltrates with variable degrees of vascular dis- ruption including fibrin deposits and thrombosis (lymphocytic vasculitis), dermal purpura and edema (Figures 26.2–26.4) (7). The overlying epithelium may undergo necrosis in conjunction with ischemic vascular thrombosis. The organisms may be positively identified within the endothelia with the aid of immunohistochemi- cal or immunofluorescent staining (8). Molecular-based methods including in situ PCR have also been utilized but are not widely available (9). Serologic methods remain the most important means of establishing a definitive diag- nosis, although they suffer from a delay in diagnosis requiring comparison of acute and convalescent antibody titers. The Weil-Felix and complement-based serologic methods are antiquated due to poor sensitivity (10).
The differential diagnosis of RMSF is broad. Important viral entities to consider include measles, rubella, and infectious mononucleosis. Measles more often presents with upper (coryza) and lower respiratory (cough) com- plaints and less often produces a petechial rash. Rubella tends to be less symptomatic than RMSF and produces a less dramatic rash that typically begins on the face. Infec- tious mononucleosis (Epstein-Barr viral infection) less often produces a rash (∼10% of patients) unless preceded
FIGURE26.1. Maculopapular erup- tion with petechial hemorrhage in Rocky Mountain Spotted Fever.
26. Rocky Mountain Spotted Fever and the Rickettsioses 127
by the administration of ampicillin. Important bacterial infections to exclude include in particular meningococ- cemia, tularemia, and leptospirosis. The rash of meningo- coccemia typically develops in conjunction with or shortly following the onset of symptoms and is often accompa- nied by leukocytosis. The rash of meningococcemia tends
to produce larger and confluent stellate configured pur- puric areas with an angulated border. Tularemia tends to produce solitary, often ulcerated or eschar-like cutaneous lesions with draining lymphadenopathy. Leptospirosis produces a rash that typically begins on the trunk, spread- ing later to the extremities. A clinical variant of leptospi- FIGURE 26.2. Low power photo-
micrograph depicting superficial and deep lymphocytic dermatitis with focal epithelial exocytosis.
Note the prominent dermal hemorrhage.
FIGURE26.3. Medium power pho- to micrograph detailing perivascu- lar lymphocytic infiltrate.
128 Deadly Dermatologic Diseases
rosis termed Fort Bragg or pretibial fever produces a petechial rash confined to the pretibial surfaces.
Empiric intravenous antibiotics should be instituted prior to biopsy or serologic confirmation as the untreated mortality approaches 30% (6). Treatment recommenda- tions are tetracycline 25–50 mg/kg q 6 hours or doxycy- cline 1 mg/lb q 12 hours or chloramphenicol 50–75 mg/kg q 6 hours for at least 7 days or until 2 days following reso- lution of symptoms. Aggressive fluid status and electrolyte balance management is essential. The overall mortality of RMSF is between 2% and 5% with appropriate antibiotic therapy. Most fatalities are observed between the eighth and fifteenth days of illness. Elderly patients and those individuals with coexisting glucose 6-phosphate dehydro- genase deficiency have been reported to have a worse prognosis.
References
1. Zaki M. Selected tickborne infections: A review of Lyme disease, Rocky Mountain Spotted Fever and babesiosis. NY State J Med 1989; 89: 320.
2. Boyd A, Neldner K. Typhus disease group. Int J Dermatol 1992; 31: 823.
3. Helmick C, Bernard K, d’Angelo L. Rocky Mountain Spotted Fever: Clinical, laboratory and epidemiological features of 262 cases. J Infect Dis 1984; 150: 480.
4. Woodward T. Rocky Mountain spotted fever: Epidemiological and early clinical signs are keys to treatment and reduced mortality. J Infect Dis 1984; 150: 465.
5. Cowan G. Rickettsial diseases: The typhus group of fevers—
a review. Postgrad Med J 2000; 76: 269.
6. Weber D, Walker D. Rocky Mountain spotted fever. Infect Dis Clin North Am 1991; 5: 19.
7. Kao G, Evancho C, Ioffe O, et al. Cutaneous histopathology of Rocky Mountain spotted fever. J Cutan Pathol 1997; 24:
604.
8. Walker C, Cain B, Olmstead P. Laboratory diagnosis of Rocky Mountain spotted fever by immunofluorescent demonstration of Rickettsia ricketsii in cutaneous lesions.
Am J Clin Pathol 1978; 69: 619.
9. Woodward T, Pederson C, Oster C, et al. Prompt confirmation of Rocky Mountain spotted fever: Identification of Rickettsiae in skin tissues. J Infect Dis 1976; 134: 297.
10. Kaplan J, Schonberger L. The sensitivity of various serologic tests in the diagnosis of Rocky Mountain spotted fever. Am J Trop Med Hyg 1986; 35: 840.
FIGURE 26.4. High power detail with perivascular lymphocytes and erythrocytes. Note fibrin deposits in proximity to the capillaries.
