Dermatoses from ticks

Ticks are ectoparasites that cause dermatologic disease directly by their bite and indirectly as vectors of bacterial, rickettsial, protozoal, and viral diseases. In North America, where ticks are the leading cause of vector-borne infection, dermatologists should recognize several tick species. Basic tick biology and identification will be reviewed. Tick bites cause a variety of acute and chronic skin lesions. The tick-borne diseases include Lyme disease, tick-borne relapsing fever, tularemia, babesiosis, Rocky Mountain spotted fever, other spotted fevers, ehrlichiosis, Colorado tick fever, and others. The epidemiology, clinical features, diagnosis, and treatment of these diseases are reviewed with an emphasis on cutaneous manifestations. Finally, the prevention of diseases caused by ticks is reviewed.     

Diagnosis and treatment of tick infestation and tick-borne diseases with cutaneous manifestations

Hard and soft ticks may be associated directly or indirectly with a number of dermatoses, both infectious and inflammatory in origin. Morbidity may occur as a result of tick bites, tick toxicosis, and even infestation. These arthropod vectors may transmit life-threatening protozoan, bacterial, rickettsial, and viral diseases with systemic and cutaneous findings. Additionally, ticks may transmit more than one pathogen with subsequent human coinfection. This article reviews the presentation of tick-borne illnesses and the medical management of these diseases. Among others, diseases such as ehrlichiosis, anaplasmosis, babesiosis, tularemia, borrelioses, tick-borne encephalitides, rickettsial spotted fevers, and tick typhus are discussed in this article. The recognition of skin manifestations associated with these diseases is paramount to early diagnosis and treatment initiation.     

Larval tick infestation: a case report and review of tick-borne disease

Tick-borne disease in the United States continues to be a threat as people interact with their natural surroundings. We present a case of an 8-year-old boy with a larval tick infestation. Ticks within the United States can carry Lyme disease, Rocky Mountain spotted fever (RMSF), ehrlichiosis, babesiosis, tularemia, tick-borne relapsing fever, and tick paralysis. These preventable diseases are treatable when accurately recognized and diagnosed; however, if left untreated, they can cause substantial morbidity and mortality. This article highlights the knowledge necessary to recognize, treat, and prevent tickborne disease.     

Fever and rash in a 3-year-old girl: Rocky Mountain spotted fever

Initial symptoms of Rocky Mountain spotted fever (RMSF), a tick-borne illness caused by Rickettsia rickettsii, are nonspecific and include headache, gastrointestinal disturbances, malaise, and myalgias, followed by fever and rash. The classic triad of fever, rash, and history of tick exposure is uncommon at presentation. Clinical manifestations of RMSF range from virtually asymptomatic to severe. Because of the potentially fatal outcome of RMSF, presumptive clinical diagnosis and empiric antimicrobial therapy can be critical. We present the case of a 3-year-old girl from New York State who presented with fever and rash.     

The rash with maculopapules and fever in adults

There is a broad differential diagnosis for the presentation of fever and maculopapular rash in an adult. Although some causative conditions are benign, others are medical emergencies that require prompt diagnosis. We describe various conditions that result in a fever and maculopapular rash in adults. These include infectious processes (meningococcemia, infectious mononucleosis, West Nile virus, zika virus, rubella, primary human immunodeficiency virus, parvovirus B19, ebolavirus), tick-borne illnesses (Rocky Mountain spotted fever, ehrlichiosis), and hypersensitivity reactions (exanthematous drug reactions). We also provide an algorithm to aid in the diagnosis of the patient with fever and maculopapular rash. Such conditions that can occur in adults but are seen predominantly in children are discussed in the article “Rash with maculopapules and fever in children” of this issue.     

Tick bite fever

Tick bite fever (boutonneuse fever) is endemic in India, Africa and especially the Mediterranean countries. It is occasionally "imported" into central European countries by tourists. The exanthematic disease is caused by infection with Rickettsia conori, which is usually transmitted by the brown dog tick. A typical primary lesion at the site of the tick's bite is an important diagnostic hint. The treatment of choice are tetracyclines.     

Vacation and tropical dermatoses

Besides fever and diarrhea, skin diseases are the third most common cause of morbidity in returning travelers after a stay in a tropical country. Approximately one- quarter of these dermatological symptoms can be referred to a classical tropical disease. The majority are of infectious origin. Often only the clinical appearance leads to the diagnosis of a tropical disease as myiasis, cutaneous larva migrans, tungiasis or cutaneous leishmaniasis. Not infrequently the dermatological symptoms lead to the diagnosis of a primarily systemic tropical disease. For example, an eschar with or without a rash might lead to the diagnosis of a South African tick bite fever caused by Rickettsia africae days before serology may turn positive. Less common tropical skin diseases such as lymphatic filariasis and loiasis need to be considered in returning long-term travelers and immigrants.     

AFRICAN TICK TYPHUS (MEDITERRANEAN SPOTTED FEVER) IN AUSTRALIAN TRAVELLERS

Two cases of infection with Rickettsia conorii in Australian travellers returned from Africa are reported in order to heighten awareness of this condition. The major clinical features are fever, an eschar, and a maculopapular rash. Diagnostic methods and treatment with tetracyclines are reviewed.     

African tick bite fever – Papulovesicular exanthem with fever after staying in South Africa

In the wake of expanding international tourism, rickettsioses are increasingly observed also in central Europe. African tick bite fever is a recently described, acute febrile illness with characteristic skin lesions.It is caused by Rickettsia africae, which is transmitted to humans by ticks of the Amblyomma genus. A 60‐year‐old woman presented with a papulovesic‐ular exanthem, fever, and headache after returning from South Africa. A purple nodule with central necrosis (“tache noire”or “inoculation eschar”) was noticed on the lower leg. Antibodies against rickettsia of the spotted fever group were detected serologically. Oral doxycycline led to clearance of the disease after few days of treatment.     

Rocky Mountain spotted fever

Rocky Mountain spotted fever (RMSF) is an unusual but important dermatological condition to identify without hesitation. The classic triad of headache, fever, and a rash that begins on the extremities and travels proximally to involve the trunk is found in a majority of patients. The cutaneous centripetal pattern is a result of cell to cell migration by the causative organism Rickettsia rickettsii. Such individuals should receive prompt antimicrobial therapy and supportive care to avoid serious and potentially fatal complications.     

Human immunodeficiency virus type 1 (HIV-1) derived vectors: safety considerations and controversy over therapeutic applications

The latest generation of lentiviral vectors based on HIV-1 is one of the most efficient tools for gene transduction of mammalian cells. However, the possible employment of HIV-based vectors in clinical trials is a very controversial issue, mainly due to safety and ethical concerns. HIV-1 is a lethal pathogenic agent, which induces AIDS. Genetic vectors must derive either from viruses that are not pathogenic in humans, or that eventually just cause mild illnesses. Patients exposed to HIV-based vectors will test seropositive to certain components of HIV-1. In addition, there might be other possible adverse effects in patients that cannot be predicted, as many aspects of the pathogenesis of AIDS have not been completely understood yet. On these grounds, it seems necessary to improve the design of other lentiviral vectors, which derive from viruses that are not pathogenic in humans and are distantly related to primate retroviridae.     

Brazilian Spotted Fever: the importance of dermatological signs for early diagnosis

Brazilian spotted fever is an acute febrile infectious disease caused by Rickettsia rickettsii, transmitted by tick bite. As this disease is rare and has high mortality rates in Brazil, the clinical aspects and epidemiological data may help the diagnosis. We report a case of Brazilian spotted fever in a 19-year-old patient who presented maculopapular exanthema in the palmar region and upper limbs, lymphadenopathy, fever, chills, headache, conjunctival hyperemia, nausea, vomiting, dyspnea, myalgia, developing neurological signs and abdominal pain. He was treated with doxycycline with clinical improvement. We emphasize the importance of the recognition of this disease by dermatologists as cutaneous manifestations are the key findings to establish early diagnosis and prevent complications.     

Cutaneous vasculitis update: neutrophilic muscular vessel and eosinophilic, granulomatous, and lymphocytic vasculitis syndromes

Most biopsies of cutaneous vasculitis will exhibit a small vessel neutrophilic vasculitis [leukocytoclastic vasculitis (LCV)] that is associated with immune complexes on direct immunofluorescence examination or, less commonly, antineutrophilic cytoplasmic antibodies (ANCA) by indirect immunofluorescence testing. Is in uncommon for skin biopsy to reveal solely a neutrophilic arteritis signifying the presence of cutaneous polyarteritis nodosa or, if accompanied by significant lobular panniculitis, nodular vasculitis/erythema induratum. In other cases, cutaneous vascular damage (fibrinoid necrosis, muscular vessel wall disruption, or endarteritis obliterans) will be mediated by a nonneutrophilic inflammatory infiltrate. Eosinophilic vasculitis can be a primary (idiopathic) process that overlaps with hypereosinophilic syndrome, or it can be a secondary vasculitis associated with connective tissue disease or parasite infestation. Authentic cutaneous granulomatous vasculitis (versus vasculitis with extravascular granulomas) can represent a cutaneous manifestation of giant cell arteritis, an eruption secondary to systemic disease such as Crohn's disease or sarcoidosis, or a localized disorder, often a post-herpes zoster (HZ) phenomenon. Lymphocytic vasculitis is a histologic reaction pattern that correlates with broad clinical differential diagnosis, which includes connective tissue disease - mostly systemic lupus erythematosus (SLE), endothelial infection by Rickettsia and viruses, idiopathic lichenoid dermatoses such as perniosis or ulcerative necrotic Mucha-Habermann disease, and angiocentric cutaneous T-cell lymphomas. Skin biopsy extending into the subcutis, identifying the dominant inflammatory cell and caliber of vessels affected, extravascular histologic clues such as presence of lichenoid dermatitis or panniculitis, and correlation with clinical data allows for accurate diagnosis of these uncommon vasculitic entities.     

Fever and Multiple Eschars After an African Safari: Report of Three Cases

African tick‐bite fever (ATBF), a tickborne disease endemic in rural areas of sub‐Saharan Africa and the West Indies caused by Rickettsia africae, has been recognized as an emerging health problem in recent years. ATBF has been reported as the second most commonly documented etiology of fever, after malaria, in travelers who return ill from sub‐Saharan Africa. Most cases reported in the literature occurred in middle‐aged adults, so the incidence of ATBF in children is unclear. We report a cluster of three cases of ATBF that occurred in children ages 7 to 16 years after returning from a game‐hunting safari in South Africa.     

Multiple pruritic papules from lone star tick larvae bites

BACKGROUND: Ticks are the second most common vectors of human infectious diseases in the world. In addition to their role as vectors, ticks and their larvae can also produce primary skin manifestations. Infestation by the larvae of ticks is not commonly recognized, with only 3 cases reported in the literature. The presence of multiple lesions and partially burrowed 6-legged tick larvae can present a diagnostic challenge for clinicians. OBSERVATION: We describe a 51-year-old healthy woman who presented to our clinic with multiple erythematous papules and partially burrowed organisms 5 days after exposure to a wooded area in southern Kentucky. She was treated with permethrin cream and the lesions resolved over the following 3 weeks without sequelae. The organism was later identified as the larva of Amblyomma species, the lone star tick. CONCLUSIONS: Multiple pruritic papules can pose a diagnostic challenge. The patient described herein had an unusually large number of pruritic papules as well as tick larvae present on her skin. Recognition of lone star tick larvae as a cause of multiple bites may be helpful in similar cases.     

Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin

Background

Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα), interleukin-12 (IL-12), and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs) delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B) of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs.

Methods

Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels.

Results

Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by immunohistological examination.

Conclusions

Our studies consolidate the properties of lentiviral vectors as a tool for potent gene delivery and for evaluation of mRNA targets for anti-inflammatory therapy. However, in contrast to local anti-TNFα treatment, the therapeutic potential of targeting IL-12B at the RNA level in psoriasis is questioned.     

Tick-borne dermatologic diseases

Inquiries regarding tick exposure can be important in dermatologic diagnosis and treatment since ticks can be vectors of a diversity of infectious diseases. The classic teaching is that ticks are best removed with nail polish, solvents, petrolatum, mineral oil, or a hot match. However, a recent evaluation of tick removal revealed that mechanical removal with forceps preceded and followed by disinfection is the most effective method. In most cases, should the characteristic dermatologic lesion or systemic symptoms appear, appropriate treatment should be initiated for presumptive diseases.     

Tularemia: the disease and the weapon

Tularemia is a bacterial infection usually transmitted via arthropod vectors or direct contact with infected animals. Naturally occurring cases are relatively rare, and can result in six different clinical syndromes. Tularemia is also a potential agent of bioterrorism or biowarfare, and is categorized as a high-level threat. Effective antibiotic treatment is available, including potential use of oral antibiotics in a mass casualty situation. An awareness of potential clinical presentations of tularemia will facilitate timely intervention,appropriate diagnostic testing, and decreased morbidity in the event of a biologic attack with Francisella tularensis.     

Filariasis: diagnosis and treatment

Filariasis is an infectious disease of the lymphatics and subcutaneous tissues caused by nematodes or filariae. Carried by mosquito vectors, this disease causes millions of people to suffer from lymphedema and elephantiasis, characteristics of filariasis infection. This disease can be diagnosed through the identification of microfilariae in blood or skin samples, antigen detection, radiographic imaging, or polymerase chain reaction. Mass drug administration by the World Health Organization has helped to diminish the incidence of filariasis. However, continued research on new drugs and vaccinations will be needed to control and reduce the microfilarial levels in the human population.