Type-I cryoglobulinemia-like histopathologic changes in tick bites: a useful clue for tissue diagnosis in the absence of tick parts

BACKGROUND: The histopathologic findings of localized reactions to tick bites may present as diagnostic dilemmas, especially if there is no history of a tick bite, or if the tick's mouthparts are not present in the biopsied skin. OBJECTIVE: Skin biopsies of patients with a clinical history of a tick bite were selected and reviewed with the aim of detecting a common histopathologic denominator which could serve as a useful clue to the diagnosis, especially when the tick's mouthparts are absent. METHODS: Hematoxylin and eosin-stained slides of 15 skin biopsies of tick bites were retrieved from three dermatopathology and pathology laboratories. Where additional paraffin-embedded tissue was available, additional sections were also stained with periodic acid-Schiff (PAS) and phosphotungstic acid-hematoxylin (PTAH). RESULTS: In every case in which adequate tissue was available (13/ 15 biopsies), the capillaries and postcapillary venules of the superficial and deep vascular plexi adjacent to the attachment's site were filled with thrombi. Fibrin thrombi were seen in association with other more numerous thrombi characterized by homogeneous eosinophilic hyaline material similar to the cryoprecipitate present in type I (monoclonal) cryoglobulinemia. All thrombi were positive for PAS and PTAH; however, the latter staining was minimally present in the hyaline thrombi. In most cases, the site of the tick bite showed ulceration, with an underlying wedge-shaped superficial and deep perivascular and occasionally interstitial mixed lymphohistiocytic infiltrate. In addition, there were eosinophils, numerous neutrophils and extravasated erythrocytes. Other findings included suppurative necrosis (7/15) cases, giant-cell reaction (one case), fat necrosis (one case) and eccrine gland necrosis (one case). CONCLUSIONS: Vascular eosinophilic hyaline thrombi were found to be a frequent histologic manifestation of a tick bite. This finding may be related to the secretory products of the tick's saliva during inoculation. We believe that a tick bite should be suspected when focal intravascular hyaline occlusion is observed, and that it should be included in the differential diagnosis of type I (monoclonal) cryoglobulinemia, even if there is no history of a tick bite or if tick parts are not present in the skin biopsy specimen.     

Thrombogenic vasculopathy with diffuse neutrophilic inflammation: a histologic manifestation of a tick bite

We describe 5 cases of tick bite reactions with dermal necrosis and sparse interstitial to dense diffuse dermal neutrophilic infiltrates associated with thrombogenic vasculopathy. Tick bite reactions classically consist of moderately dense perivascular infiltrates composed of an admixture of inflammatory cells. Each of our patients had embedded tick parts, with interesting histologic features.     

African tick bite fever: a not-so-uncommon illness in international travelers

BACKGROUND: African tick bite fever is a rickettsial illness that has recently emerged as a significant disease among international travelers. The vector is the Amblyomma tick, which is endemic to sub-Saharan Africa and parts of the eastern Caribbean. OBSERVATIONS: We describe a middle-aged woman who returned from a mission trip to Zimbabwe with an influenzalike illness and inoculation eschar; she also had a history of travel to a game farm. Biopsy revealed a histopathologic pattern consistent with an infectious pathogenesis. Immunohistochemical staining confirmed the presence of rickettsial organisms. In light of the patient's history, the clinical constellation of signs and symptoms, and the results of ancillary laboratory testing, a diagnosis of African tick bite fever was made. The patient was treated with doxycycline hydrochloride and had an uncomplicated course. CONCLUSIONS: This report further highlights the epidemiological and clinical features of African tick bite fever. With the increase in international travel, it is important to recognize the illness in those who have been to endemic countries and to counsel patients regarding preventive measures for planned travel.     

Tick bite mimicking indeterminate cell histiocytosis

Ticks are a well‐known vector for viral, bacterial, and rickettsial infections, many of which are accompanied by cutaneous eruptions, but the bite itself can induce a spectrum of inflammatory reactions, including foreign body granuloma, tick bite alopecia, and cutaneous lymphoid hyperplasia. We describe the development of an indeterminate cell histiocytic infiltrate at the site of a tick bite. Although the etiology of intermediate cell histiocytosis is not well understood, this case raises the possibility that such infiltrates may represent an inflammatory reaction in some patients.     

Cutaneous histopathology of the tick‐bite region in severe fever with thrombocytopenia syndrome

A case of severe fever with thrombocytopenia syndrome (SFTS) in which a skin biopsy from the tick‐bite region was analyzed is reported. The patient was a 72‐year‐old woman who developed fever and thrombocytopenia after a tick bite. SFTS was diagnosed from polymerase chain reaction (PCR) analysis of a blood sample. Histopathological analysis of a skin biopsy specimen from the tick‐bite region showed CD20‐positive perivascular and interstitial immunoblastic cells, which were positive to anti‐SFTS virus (SFTSV) nucleoprotein antibody. In addition, SFTSV RNA was detected by real‐time PCR from this biopsy specimen. Moreover, hemophagocytosis was also found in the tick‐bite region. To the best of our knowledge, this is the first report to analyze the details of the tick‐bite region of skin in SFTS, and the first to detect virus‐infected cells in the skin. The present findings may help elucidate the mechanisms of entry of SFTSV.     

Tick bite by Haemaphysalis megaspinosa - first case

We describe the first case of tick bite by Haemaphysalis megaspinosa. The tick was found on the skin at the right occipital area in a 5-year-old girl, who had gone on a picnic twice to a mountain 1 and 5 days before she noticed the tick. The tick was surgically removed. The tick was identified as an adult female of Haemaphysalis megaspinosa from its morphological characteristics. This is the first report of tick bite by Haemaphysalis megaspinosa.     

A case of tick bite with Ixodes turdus Nakatsuji--a report from Japan

The first case of tick bite by Ixodes turdus Nakatsuji was reported. The tick was found on the occipital area near the left ear of a 6-year-old boy. The tick bite occurred in Hoya, a suburb of Tokyo.     

Laboratory observations of Haemaphysalis longicornis Neumann after a human bite

A case of a tick bite with Haemaphysalis longicornis Neumann is reported. The tick was found on the left lower abdomen of a 62-year-old female. The tick bite occurred in Fuchu city, a suburb of Tokyo. This paper presents laboratory observations of the process of Haemaphysalis longicornis Neumann laying eggs and becoming larvae after biting a human. The results of our observations include the size of female adult (length: 7.5 mm, width: 5.2 mm, weight: 96 mg) after blood sucking, preoviposition period (7 days), oviposition period (24 days), number of eggs (760 eggs), egg size (length: 0.58-0.62 mm, width: 0.39-0.42 mm), size of unfed larva (length: 0.45-0.5 mm, width: 0.45-0.5 mm) and unfed larva period until death, which ranged from 10 days to 62 days.     

A Case of Tick Bite from Amblyomma testudinarium on the Glans Penis

A tick which bit the glans penis of a 40-year-old Japanese man was surgically excised together with the skin where the bite occurred. It was identified as Amblyomma testudinarium through the taxonomical investigation of its morphological characteristics. To our best knowledge, our patient is the sixth tick bite from this species of tick recorded in the Chugoku District of Japan.     

Case of tick‐associated rash illness caused by Amblyomma testudinarium

We report a case of tick‐associated rash illness (TARI), a new clinical entity of erythema migrans associated with a tick bite without infection of Lyme borreliosis agent. The patient, a 53‐year‐old man, went hiking in a mountainous area of Minoh City, Osaka Prefecture in October 2012. An erythematous macule with itching and a biting tick was found on his left thigh 2 days later, which gradually expanded. On the first visit to our department at the fifth day after hiking, an erythematous macule of 10 cm was recognized around the bite site. He had no systemic symptoms, and laboratory data were within normal limits. The tick was identified as a nymph of Amblyomma testudinarium. Histopathologically, perivascular infiltrates, mainly consisting of T lymphocytes, were seen in the dermis. The skin rash disappeared within 2 weeks with no treatment. Serum antibody titers against Lyme disease borrelial and rickettsial agents on the first visit and 2 weeks later were negative. These results indicate that the skin lesion of TARI was not associated with borrelial or rickettsial infection but a T‐cell‐mediated allergic reaction to salivary gland substances of the tick.     

Persistent pruritic papules from deer ked bites

Deer ked (Lipoptena cervi L.), a haematophagous louse fly of deer, also attacks man and can cause persistent pruritic papules. Nineteen patients with this conditions were examined. They suffered attacks while carrying out their work, or merely walking, in forested areas. The bite papules appeared mostly on the head and back. They were very itchy and resistant to treatment and persisted from 2 weeks up to 12 months. Histologically, a typical insect bite reaction was found without any signs of retained deer ked mouth parts. Direct immunofluorescence showed deposits of C3 in dermal vessel walls in 7 of the 11 papules examined. Skin tests with a deer ked whole body extract were positive in all patients tested, showing both immediate and delayed reactions. Moreover, 57% of the patients tested had elevated serum IgE levels. All these findings suggest that IgE, complement and cell-mediated immune mechanisms are involved in the pathogenesis of deer ked bite reactions.     

The spirochetal etiology of lymphadenosis benigna cutis solitaria

Ten patients with a clinical diagnosis of lymphadenosis benigna cutis (LABC) solitaria were investigated. Four of the patients knew that they had received a tick bite during the year prior to the appearance of the LABC lesion. Five patients had had a migrating erythema, indicating a previous erythema chronicum migrans Afzelius, near the site where the LABC lesion had developed. In one patient meningitis and a facial palsy occurred. Elevated titers of antibodies against Borrelia spirochetes were found in sera from six of nine patients. Spirochetes were cultivated from one out of two biopsies from LABC lesions. The clinical findings, the results of the serologic tests and the successful cultivation of spirochetes show that Ixodes ricinus-transmitted Borrelia spirochetes can cause LABC solitaria.     

Five cases of tick bite

Reported here are five cases of tick bite: in a 2-year-old boy, a 3-year-old girl, a 72-year-old woman, a 29-year-old woman, and a 51-year-old man. Four cases are thought to have occurred in a mountain area while one occurred in a city garden. None were accompanied with severe systemic symptoms or deuteropathies. The parasites were identified as the adult female tick Ixodes ovatus Neumann (3 cases) and Ixodes nipponensis Kitaoka et Saito (2 cases), which are commonly distributed in Japan.     

Amblyomma testudinarium tick bite: one case of engorged adult and a case of extraordinary number of larval tick infestation

This paper reports two recent cases of tick bite due to Amblyomma testudinarium. The first case was an 86-year-old farmer infested with a fully engorged adult tick attached on his inguinal region. The second case was a 57-year-old male infested with an extraordinarily large number of larval ticks (> 100 larvae). The ticks were identified as A. testudinarium based on morphological characteristics. To our knowledge, the latter case is the eleventh case of larval tick bites among all tick species and the fourth case with larval A. testudinarium in Japan.     

A case of tick bite

A case of tick bite in a 4-year-old Japanese boy is reported. The parasite was identified as an adult female tick, Ixodes persulcatus Schulze, which is one of the most common ticks in Japan.     

Delayed appearance of symptoms in immediate hypersensitivity: type I sensitization to galactose-α-1,3-galactose

Delayed immediate-type allergy to innards and red meat can be mediated by IgE antibodies to galactose-α-1, 3-galactose (α-Gal). Apart from humans and Old World apes, α-Gal is ubiquitously expressed in glycoproteins and glycolipids. Thus, as α-Gal is immunogenic for humans, they can be easily sensitized even through a tick bite. Anti-α-Gal IgG represents approximately 1% of total IgG; IgE antibodies to α-Gal are comparably rare. However, in these patients, consuming red meat and especially innards can lead to the development of immediate type reactions such as urticaria. Cetuximab is a humanized IgG1 antibody containing murine α-Gal. Therefore, allergic reactions may occur with its first administration.     

Prominent Langerhans' cell migration in the arthropod bite reactions simulating Langerhans' cell histiocytosis

BACKGROUND: Epidermal Langerhans' cells (LCs) play pivotal roles in cutaneous immune responses. An encounter with antigens or other stimuli causes the mobilization and migration of LCs. Therefore, some dermatoses, which originated from antigenic stimuli or trauma, can show LC migration. Recently, we experienced several cases of anthropod bites that showed marked inflammatory infiltrates with eosinophils and CD1a-positive LCs. It was difficult to differentiate these cases from Langerhans' cell histiocytosis (LCH). METHODS: The degree and pattern of LC infiltration in the skin of arthropod bite reaction was evaluated. The characteristics of CD1a immunohistochemical expression in the arthropod bite reactions were compared with those of LCH. RESULTS: A few arthropod bite cases (approximately 36%) showed extensive CD1a-positive LCs in the dermis, especially in the perivascular area. In addition, the CD1a expression patterns of LCs in the arthropod bite reactions were dendritic, whereas that of tumor cells in LCH were distinctly membranous and cytoplasmic. CONCLUSION: Some arthropod bite reactions can show marked CD1a-positive LCs in the dermis, especially in the perivascular area. The dendritic CD1a immunohistochemical staining pattern in arthropod bite reactions is useful in helping to differentiate from LCH.     

Persistent atypical lymphocytic hyperplasia following tick bite in a child: report of a case and review of the literature

We report a 6-year-old girl who developed a red papule on the posterior neck at the site of a previous tick bite. Initial biopsy was performed a year after the bite and the specimen showed a dense lymphoid infiltrate with admixed CD30+ cells. The patient was referred to our center because of concern about the development of a CD30+ lymphoproliferative disorder. The lesion was completely excised. Histology showed no evidence of a clonal lymphoproliferative disorder or Borrelia infection, but persistence of CD30+ cells. This case demonstrates that a tick bite reaction can persist for more than 1 year and show immunophenotypic and morphologic overlap with a CD30+ lymphoproliferative disorder. Complete history with thorough clinical and histopathologic evaluation is necessary to arrive at the correct diagnosis.     

Lymphocytoma--a borreliosis?

4 patients suffering from lymphocytoma had been observed for a mean of 1.75 years (13 to 21 month). The lesions were located on the ears; all patients developed regional lymphadenopathy. Two patients experienced headaches of short duration, one child showed six erythema migrans lesions, and another child had an elevated IgM level of 322 mg/dl. A tick bite was noted in one child. Indirect immunofluorescence tests revealed significantly elevated IgG or IgM antibody titers against Ixodes dammini and Ixodes ricinus spirochetes in all patients. Serological evaluation may be helpful in differentiating borrelial lymphocytoma from other pseudolymphomas.     

Characterization of the early local immune response to Ixodes ricinus tick bites in human skin

Little is known about the immunomodulation by tick saliva during a natural tick bite in human skin, the site of the tick‐host interaction. We examined the expression of chemokines, cytokines and leucocyte markers on the mRNA levels and histopathologic changes in human skin biopsies of tick bites (n=37) compared to unaffected skin (n=9). Early tick‐bite skin lesions (<24 hours of tick attachment) were characterized by a predominance of macrophages and dendritic cells, elevated mRNA levels of macrophage chemoattractants (CCL2, CCL3, CCL4) and neutrophil chemoattractants (CXCL1, CXCL8), of the pro‐inflammatory cytokine, IL‐1β, and the anti‐inflammatory cytokine, IL‐5. In contrast, the numbers of lymphocytes and mRNA levels of lymphocyte cell markers (CD4, CD8, CD19), lymphocyte chemoattractants (CXCL9, CXCL10, CXCL11, CXCL13, CCL1, CCL22), dendritic cell chemoattractants (CCL20), and other pro‐ (IL‐6, IL‐12p40, IFN‐γ, TNF‐α) and anti‐inflammatory cytokines (IL‐4, IL‐10, TGF‐β) did not differ from normal skin. With longer tick attachment (>24 hours), the numbers of innate immune cells and mediators (not significantly) declined, whereas the numbers of lymphocytes (not significantly) increased. Natural tick bites by Ixodes ricinus ticks initially elicit a strong local innate immune response in human skin. Beyond 24 hours of tick attachment, this response usually becomes less, perhaps because of immunomodulation by tick saliva.