P ediatric and D eve lo p m e n ta l P a th o lo g y 18, 164-166, 2015 DOI: 10.2350/14-08-1545-CR.1 © 2015 Society fo r P ediatric P athology
A Five-Year-Old Child with a Subcutaneous Forehead Nodule Lars F. W estblade, 1,2* P eter U. Fischer, 3 N ina H ag hi, 4 M atthew J. Schniederjan , 1,2 Bobbi S. Pritt, 5 John G. Long , 6 R obert C. Jerris, 1,2 and R obert E. G arola 7 ,8 ’ Department o f Pathology, Children's Healthcare o f Atlanta, Atlanta, GA, USA d e p a rtm e n t o f Pathology and Laboratory Medicine, Emory University School o f Medicine, Atlanta, GA, USA in fe ctio u s Diseases Division, Department o f Internal Medicine, Washington University in St. Louis School o f Medicine, St. Louis, MO, USA d e p a rtm e n t o f Pathology and Laboratory Medicine, Hofstra North Shore-LIJ School o f Medicine, Hempstead, NY, USA d iv is io n of Clinical Microbiology, Mayo Clinic, Rochester, MN, USA sPediatric Infectious Disease Associates of Atlanta, PC, Atlanta, GA, USA d e p a rtm e n t of Pathology and Laboratory Medicine, Children's Mercy Hospital, Kansas City, MO, USA 8The University o f Missouri at Kansas City School of Medicine, Kansas City, MO, USA
Received August 28, 2014; accepted January
5,
2015; published online January 8, 2015.
ABSTRACT We describe a case of a 5-year-old girl with onchocer ciasis. The patient was recently adopted from Ethiopia and presented with a firm, raised nodule on the midportion of the forehead. Initially, Langerhans cell histiocytosis with bone involvement was suspected; however, histopathologic analysis of the excised nodule revealed the presence of a young-adult, female Oncho cerca volvulus worm. This case exemplifies the impor tance of recognizing the key morphologic characteristics of adult O. volvulus worms isolated from pediatric patients in nonendemic areas to ensure adroit clinical management. Key words: doxycycline, filariasis, ivermectin, oncho cerca, onchocerciasis, Wolbachia
CASE REPORT A 5-year-old girl residing in Georgia, United States, presented with an approximately 6 month history of a firm, raised nodule 2 by 2 cm on the midportion of the forehead. About 1 month before presentation, the patient was adopted from Ethiopia. Radiologic analysis of the skull showed a small soft tissue mass with abnormal scalloping/erosion of the outer table of the frontal bone, although no fracture was observed. Upon initial evalua tion, Langerhans cell histiocytosis with bone involvement was suspected. A diagnostic incisional biopsy revealed that the mass was easily separated from the overlying skin and soft tissue and underlying bone, and the specimen was sent for histopathologic examination. The specimen received in the laboratory consisted of a 1.5 by 1.2 by * Corresponding author, e-mail: [email protected]
0.8 cm, pink-red, rubbery, and focally cauterized portion of soft tissue. A hematoxylin and eosin-stained section was prepared and microscopically examined. Inspection of the hematoxylin and eosin-stained section showed stromal tissue with multiple cross-sections of a young-adult, female Onchocerca volvulus worm [1] (Fig. 1). No developing or mature microfilariae (larvae) were detected in the uterine branches or the nodular tissue. In pediatric patients, nodules with young-adult, female worms, often alone, are common [1], Diagnosis is often difficult in nonendemic areas because young female worms do not yet produce microfilariae, which are definitively diagnostic for onchocerciasis when detected in the skin [2]. Further, as exemplified by our case, despite travel history, the clinical presentation of onchocerciasis is often greatly underappreciated in nonendemic areas. The filarial nem atode O. volvulus is the causative agent of onchocerciasis, also known as African River Blindness because of the close association between this vector-bome disease and fast flowing rivers and streams. An estimated 37 million people in 34 countries in sub-Saharan Africa (including Ethiopia), Yemen, and in South America are infected with O. volvulus [3], The O. volvulus life cycle is dependent on the definitive human host and the Simulium species blackfly intermediate host that breeds in oxygen-rich rivers [2]. Adult worms live in the subcutaneous and deeper tissues within fibrous connective tissue nodules called onchocercomas. Onchocercomas sometimes contain more than one adult worm (macrofilariae), with females measuring 35 to 70 cm long and 0.4 mm in diameter, and males measuring 2 to 5 cm long by 0.2 mm. Mature, adult, female worms produce unsheathed microfilariae, which measure 300 by 8 pm, with a sharply pointed tail and head devoid of nuclei. Microfilariae are typically found in the
Figure 1. A. H em atoxylin and eosin-sta ine d cross-section o f th e onchocercom a sh ow ing several cross-sections o f a yo un ga d u lt, fe m a le w o rm surrou nd ed by a dense p o p u la tio n o f in fla m m a to ry cells (o rig in a l m a g n ific a tio n X40). B. Single section th ro u g h th e w o rm w ith in th e onchocercom a a t h ig h e r m a g n ific a tio n . The key dia gn ostic fe atures include th e cu ticu la r rings (darts), p aired u te rin e branches co n ta in in g oocytes (black arrow s) and th e intestin e (w h ite a rro w ) (o rig in a l m a g n ific a tio n x200). Males have a sm aller d ia m e te r and o n ly one re p ro d u ctive tu b e b u t w e re n o t seen in th is specimen.
skin and lymphatic vessels and are ingested by blackflies as they feed on blood. Within the blackfly, microfilariae develop into infective larvae over a period of 6 to 12 days and are deposited onto human skin during a subsequent blood meal, where they enter the bite wound. Infective larvae develop into sexually mature adult worms. During reproductive periods, mature female worms can produce thousands of microfilariae a day for an estimated 9 to 11 years. The prepatent period in the human host (the time between infection and the appearance of microfilariae in the skin) is typically 10 to 15 months. The spectrum of disease presentations due to O. volvulus range from light, asymptomatic infections to acute and chronic dermatitis to visual impairment and blindness [2], The cutaneous and ocular manifestations occur in response to death of microfilariae in the skin and eye, respectively. There is some evidence that Wolbachia, endosymbiotic bacteria in O. volvulus, are important
drivers of pathogenesis of onchocerciasis [4], The most common cutaneous manifestation of onchocerciasis is papular dermatitis with pruritus, whereas more chronic changes can include atrophy, hyperkeratosis, and abnor mal pigmentation. The most debilitating outcome of onchocerciasis is visual impairment and blindness. In 1995, the World Health Organization estimated that 17.7 million individuals worldwide were infected with O. volvulus with up to 270 000 cases of blindness and 500 000 cases of severe visual impairment [2], The primary treatment for onchocerciasis is ivermec tin (a semisynthetic, macrocyclic lactone), which blocks nematode glutamate-gated ion channels. Ivermectin temporarily sterilizes adult, female worms by inhibiting the release of uterine microfilariae, while skin and ocular microfilariae are immobilized and ultimately killed [2], Ivermectin treatment can be hazardous in patients in Central Africa who are coinfected with the filarial A C hild with a Subcutaneous Scalp N odule
165
/
*
\,
Figure 2. Wolbachia im m u no stain (ant\-Wolbachia o u te r surface p ro te in [GenBank accession num ber: AAW 71020]) o f a cross-section o f th e y o u n g -a d u lt, fe m a le w o rm o b ta in e d fro m o u r p a tie n t. Labeled Wolbachia (green dots a p p ro x im a te ly 500 nm in d ia m e te r) are co nce ntra ted in th e lateral chords and hypoderm is o f th e w o rm . Few labeled Wolbachia w ere observed in th e oocytes w ith in th e u te rin e branches. A lth o u g h Wolbachia are associated w ith all fila ria l nem atodes o f m edical im p o rta n ce (except Loa loa), to g e th e r th e clinical pre sen ta tion , h isto p a th o lo g y, and positive Wolbachia im m u no stain was d e fin itiv e fo r Onchocerca volvulus in th is case.
nematode Loa loa. Patients with heavy L. loa infections sometimes experience severe adverse events, including coma and even death, following ivermectin therapy [2,5], Throughout all life cycle stages, and as observed with our patient (Fig. 2), O. volvulus is associated with the essential endosymbiotic bacterium Wolbachia. As such, anti -Wolbachia therapies, including doxycycline (a ster ilization agent and macrofilaricide), are an evolving treatment strategy for onchocerciasis [2,4]. In addition to O. volvulus, all filarial nematodes of medical importance, with the exception of L. loa, rely on Wolbachia symbiosis
[6],
166
L.F. W estblade
et al .
Before the administration of antifilarial therapy, a thorough ophthalmologic examination of our patient’s eyes to detect microfilariae was performed. To increase the sensitivity of detecting O. volvulus microfilariae in the anterior chamber, the patient was asked to sit with their head between their knees for 10 minutes immediately before examination [7]. Additionally, venous blood was drawn between 10 am and 2 pm to detect L. loa microfilaremia [8]. Both the eye examination and microscopic analysis of thin and thick venous blood smears were negative. Subsequently, oral ivermectin therapy was initiated, and the patient remains symptom free. In conclusion, our case exemplifies the importance of recognizing the key morphologic characteristics of adult 0. volvulus worms isolated from pediatric patients in nonendemic areas to ensure efficient and appropriate clinical management. REFERENCES 1. Specht S, Brattig N, Biittner M, Biittner DW. Criteria for the differentiation between young and old Onchocerca volvulus filariae. Parasitol Res 2009;105:1531-1538. 2. Simonsen PE, Fischer PU, Hoerauf A, Weil GJ. The filariases. In: Farrar J, Hotez PJ, Junghanss T, Kang G, Lalloo D, White N, eds. Manson’s Tropical Diseases. Philadelphia: Saunders; 2013:737-765. 3. Basanez MG, Pion SDS, Churcher TS, Breitling LP, Little MP, Boussinesq M. River blindness: a success story under threat? PLoS Med 2006;3:e371. 4. Tamarozzi F, Halliday A, Gentil K, Hoerauf A, Pearlman E, Taylor MJ. Onchocerciasis: the role of Wolbachia bacterial endosymbionts in parasite biology, disease pathogenesis, and treatment. Clin Microbiol Rev 2011;24:459^168. 5. Gardon J, Gardon-Wendel N, Demanga-Ngangue, Kamgno J, Chippaux JP. Boussinesq M. Serious reactions after mass treatment of onchocerciasis with ivennectin in an area endemic for Loa loa infection. Lancet 1997;350:18-22. 6. Taylor MJ, Voronin D, Johnston KL, Ford L. Wolbachia filarial interactions. Cell Microbiol 2013;15:520-526. 7. Thylefors B, Brinkmann UK. The microfilarial load in the anterior segment of the eye. A parameter of intensity of onchocerciasis. Bull World Health Organ 1977;55:731-737. Eberhard ML, Lammie PJ. Laboratory diagnosis of filariasis. Clin Lab Med 1991;11:977-1010.
Copyright of Pediatric & Developmental Pathology is the property of Allen Press Publishing Services Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
A Five-Year-Old Child with a Subcutaneous Forehead Nodule Lars F. W estblade, 1,2* P eter U. Fischer, 3 N ina H ag hi, 4 M atthew J. Schniederjan , 1,2 Bobbi S. Pritt, 5 John G. Long , 6 R obert C. Jerris, 1,2 and R obert E. G arola 7 ,8 ’ Department o f Pathology, Children's Healthcare o f Atlanta, Atlanta, GA, USA d e p a rtm e n t o f Pathology and Laboratory Medicine, Emory University School o f Medicine, Atlanta, GA, USA in fe ctio u s Diseases Division, Department o f Internal Medicine, Washington University in St. Louis School o f Medicine, St. Louis, MO, USA d e p a rtm e n t o f Pathology and Laboratory Medicine, Hofstra North Shore-LIJ School o f Medicine, Hempstead, NY, USA d iv is io n of Clinical Microbiology, Mayo Clinic, Rochester, MN, USA sPediatric Infectious Disease Associates of Atlanta, PC, Atlanta, GA, USA d e p a rtm e n t of Pathology and Laboratory Medicine, Children's Mercy Hospital, Kansas City, MO, USA 8The University o f Missouri at Kansas City School of Medicine, Kansas City, MO, USA
Received August 28, 2014; accepted January
5,
2015; published online January 8, 2015.
ABSTRACT We describe a case of a 5-year-old girl with onchocer ciasis. The patient was recently adopted from Ethiopia and presented with a firm, raised nodule on the midportion of the forehead. Initially, Langerhans cell histiocytosis with bone involvement was suspected; however, histopathologic analysis of the excised nodule revealed the presence of a young-adult, female Oncho cerca volvulus worm. This case exemplifies the impor tance of recognizing the key morphologic characteristics of adult O. volvulus worms isolated from pediatric patients in nonendemic areas to ensure adroit clinical management. Key words: doxycycline, filariasis, ivermectin, oncho cerca, onchocerciasis, Wolbachia
CASE REPORT A 5-year-old girl residing in Georgia, United States, presented with an approximately 6 month history of a firm, raised nodule 2 by 2 cm on the midportion of the forehead. About 1 month before presentation, the patient was adopted from Ethiopia. Radiologic analysis of the skull showed a small soft tissue mass with abnormal scalloping/erosion of the outer table of the frontal bone, although no fracture was observed. Upon initial evalua tion, Langerhans cell histiocytosis with bone involvement was suspected. A diagnostic incisional biopsy revealed that the mass was easily separated from the overlying skin and soft tissue and underlying bone, and the specimen was sent for histopathologic examination. The specimen received in the laboratory consisted of a 1.5 by 1.2 by * Corresponding author, e-mail: [email protected]
0.8 cm, pink-red, rubbery, and focally cauterized portion of soft tissue. A hematoxylin and eosin-stained section was prepared and microscopically examined. Inspection of the hematoxylin and eosin-stained section showed stromal tissue with multiple cross-sections of a young-adult, female Onchocerca volvulus worm [1] (Fig. 1). No developing or mature microfilariae (larvae) were detected in the uterine branches or the nodular tissue. In pediatric patients, nodules with young-adult, female worms, often alone, are common [1], Diagnosis is often difficult in nonendemic areas because young female worms do not yet produce microfilariae, which are definitively diagnostic for onchocerciasis when detected in the skin [2]. Further, as exemplified by our case, despite travel history, the clinical presentation of onchocerciasis is often greatly underappreciated in nonendemic areas. The filarial nem atode O. volvulus is the causative agent of onchocerciasis, also known as African River Blindness because of the close association between this vector-bome disease and fast flowing rivers and streams. An estimated 37 million people in 34 countries in sub-Saharan Africa (including Ethiopia), Yemen, and in South America are infected with O. volvulus [3], The O. volvulus life cycle is dependent on the definitive human host and the Simulium species blackfly intermediate host that breeds in oxygen-rich rivers [2]. Adult worms live in the subcutaneous and deeper tissues within fibrous connective tissue nodules called onchocercomas. Onchocercomas sometimes contain more than one adult worm (macrofilariae), with females measuring 35 to 70 cm long and 0.4 mm in diameter, and males measuring 2 to 5 cm long by 0.2 mm. Mature, adult, female worms produce unsheathed microfilariae, which measure 300 by 8 pm, with a sharply pointed tail and head devoid of nuclei. Microfilariae are typically found in the
Figure 1. A. H em atoxylin and eosin-sta ine d cross-section o f th e onchocercom a sh ow ing several cross-sections o f a yo un ga d u lt, fe m a le w o rm surrou nd ed by a dense p o p u la tio n o f in fla m m a to ry cells (o rig in a l m a g n ific a tio n X40). B. Single section th ro u g h th e w o rm w ith in th e onchocercom a a t h ig h e r m a g n ific a tio n . The key dia gn ostic fe atures include th e cu ticu la r rings (darts), p aired u te rin e branches co n ta in in g oocytes (black arrow s) and th e intestin e (w h ite a rro w ) (o rig in a l m a g n ific a tio n x200). Males have a sm aller d ia m e te r and o n ly one re p ro d u ctive tu b e b u t w e re n o t seen in th is specimen.
skin and lymphatic vessels and are ingested by blackflies as they feed on blood. Within the blackfly, microfilariae develop into infective larvae over a period of 6 to 12 days and are deposited onto human skin during a subsequent blood meal, where they enter the bite wound. Infective larvae develop into sexually mature adult worms. During reproductive periods, mature female worms can produce thousands of microfilariae a day for an estimated 9 to 11 years. The prepatent period in the human host (the time between infection and the appearance of microfilariae in the skin) is typically 10 to 15 months. The spectrum of disease presentations due to O. volvulus range from light, asymptomatic infections to acute and chronic dermatitis to visual impairment and blindness [2], The cutaneous and ocular manifestations occur in response to death of microfilariae in the skin and eye, respectively. There is some evidence that Wolbachia, endosymbiotic bacteria in O. volvulus, are important
drivers of pathogenesis of onchocerciasis [4], The most common cutaneous manifestation of onchocerciasis is papular dermatitis with pruritus, whereas more chronic changes can include atrophy, hyperkeratosis, and abnor mal pigmentation. The most debilitating outcome of onchocerciasis is visual impairment and blindness. In 1995, the World Health Organization estimated that 17.7 million individuals worldwide were infected with O. volvulus with up to 270 000 cases of blindness and 500 000 cases of severe visual impairment [2], The primary treatment for onchocerciasis is ivermec tin (a semisynthetic, macrocyclic lactone), which blocks nematode glutamate-gated ion channels. Ivermectin temporarily sterilizes adult, female worms by inhibiting the release of uterine microfilariae, while skin and ocular microfilariae are immobilized and ultimately killed [2], Ivermectin treatment can be hazardous in patients in Central Africa who are coinfected with the filarial A C hild with a Subcutaneous Scalp N odule
165
/
*
\,
Figure 2. Wolbachia im m u no stain (ant\-Wolbachia o u te r surface p ro te in [GenBank accession num ber: AAW 71020]) o f a cross-section o f th e y o u n g -a d u lt, fe m a le w o rm o b ta in e d fro m o u r p a tie n t. Labeled Wolbachia (green dots a p p ro x im a te ly 500 nm in d ia m e te r) are co nce ntra ted in th e lateral chords and hypoderm is o f th e w o rm . Few labeled Wolbachia w ere observed in th e oocytes w ith in th e u te rin e branches. A lth o u g h Wolbachia are associated w ith all fila ria l nem atodes o f m edical im p o rta n ce (except Loa loa), to g e th e r th e clinical pre sen ta tion , h isto p a th o lo g y, and positive Wolbachia im m u no stain was d e fin itiv e fo r Onchocerca volvulus in th is case.
nematode Loa loa. Patients with heavy L. loa infections sometimes experience severe adverse events, including coma and even death, following ivermectin therapy [2,5], Throughout all life cycle stages, and as observed with our patient (Fig. 2), O. volvulus is associated with the essential endosymbiotic bacterium Wolbachia. As such, anti -Wolbachia therapies, including doxycycline (a ster ilization agent and macrofilaricide), are an evolving treatment strategy for onchocerciasis [2,4]. In addition to O. volvulus, all filarial nematodes of medical importance, with the exception of L. loa, rely on Wolbachia symbiosis
[6],
166
L.F. W estblade
et al .
Before the administration of antifilarial therapy, a thorough ophthalmologic examination of our patient’s eyes to detect microfilariae was performed. To increase the sensitivity of detecting O. volvulus microfilariae in the anterior chamber, the patient was asked to sit with their head between their knees for 10 minutes immediately before examination [7]. Additionally, venous blood was drawn between 10 am and 2 pm to detect L. loa microfilaremia [8]. Both the eye examination and microscopic analysis of thin and thick venous blood smears were negative. Subsequently, oral ivermectin therapy was initiated, and the patient remains symptom free. In conclusion, our case exemplifies the importance of recognizing the key morphologic characteristics of adult 0. volvulus worms isolated from pediatric patients in nonendemic areas to ensure efficient and appropriate clinical management. REFERENCES 1. Specht S, Brattig N, Biittner M, Biittner DW. Criteria for the differentiation between young and old Onchocerca volvulus filariae. Parasitol Res 2009;105:1531-1538. 2. Simonsen PE, Fischer PU, Hoerauf A, Weil GJ. The filariases. In: Farrar J, Hotez PJ, Junghanss T, Kang G, Lalloo D, White N, eds. Manson’s Tropical Diseases. Philadelphia: Saunders; 2013:737-765. 3. Basanez MG, Pion SDS, Churcher TS, Breitling LP, Little MP, Boussinesq M. River blindness: a success story under threat? PLoS Med 2006;3:e371. 4. Tamarozzi F, Halliday A, Gentil K, Hoerauf A, Pearlman E, Taylor MJ. Onchocerciasis: the role of Wolbachia bacterial endosymbionts in parasite biology, disease pathogenesis, and treatment. Clin Microbiol Rev 2011;24:459^168. 5. Gardon J, Gardon-Wendel N, Demanga-Ngangue, Kamgno J, Chippaux JP. Boussinesq M. Serious reactions after mass treatment of onchocerciasis with ivennectin in an area endemic for Loa loa infection. Lancet 1997;350:18-22. 6. Taylor MJ, Voronin D, Johnston KL, Ford L. Wolbachia filarial interactions. Cell Microbiol 2013;15:520-526. 7. Thylefors B, Brinkmann UK. The microfilarial load in the anterior segment of the eye. A parameter of intensity of onchocerciasis. Bull World Health Organ 1977;55:731-737. Eberhard ML, Lammie PJ. Laboratory diagnosis of filariasis. Clin Lab Med 1991;11:977-1010.
Copyright of Pediatric & Developmental Pathology is the property of Allen Press Publishing Services Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
