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| ORIGINAL ARTICLE |
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| Year : 2020 | Volume
: 7
| Issue : 2 | Page : 102-107 |
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Infectious granulomatous dermatitis: Clinicohistopathological study with some unusual clinical presentation
Praneeta Jaswant Singh, Ambrish Kumar
Department of Pathology, KD Medical College Hospital and Research Center, Mathura, Uttar Pradesh, India
| Date of Submission | 17-Oct-2020 |
| Date of Acceptance | 02-Dec-2020 |
| Date of Web Publication | 21-Dec-2020 |
Correspondence Address:
Dr. Praneeta Jaswant Singh
Department of Pathology, KD Medical College Hospital and Research Center, Akbarpur, Mathura - 281 406, Uttar Pradesh
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/ami.ami_130_20
Introduction: Granulomatous dermatitis has a varied differential diagnosis ranging from infectious etiology to immune mediated diseases. In tropical countries like India, infectious etiology forms an important cause of granulomatous dermatitis with tuberculosis (TB) and leprosy being the major contributing factors. The present study was carried out with the aim to determine the frequency of various etiological agents causing infectious granulomatous dermatitis in our hospital setup and to see clinicohistopathological correlation in these cases. Materials and Methods: This is a hospital based retrospective study conducted in the department of pathology over a period of 1 year. All the skin biopsy cases diagnosed as infectious granulomatous dermatitis were retrieved from the histopathology record section for analysis and were categorized based on the causative etiological agents. Special stains were applied wherever necessary in addition to routine hematoxylin and eosin stain. Results: A total of 40 cases of infectious granulomatous dermatitis were included in the present study. Most common diagnosis was leprosy (57.5%), followed by TB (30.0%), actinomycosis (5.0%), dermatophytosis (2.5%), histoplasmosis (2.5%), and cysticercosis (2.5%). Gender wise distribution showed male predominance with 57.5% of cases and age wise distribution showed a peak in the age group of 41–60 years (32.5%). Clinicohistopathological correlation was found in 87.50% of the cases. The unusual clinical presentations were seen in cases of cysticercosis, actinomycosis, and histoplasmosis. Conclusion: Histopathological examination of the skin biopsies is an important diagnostic tool providing definitive diagnosis as well as clinicohistopathological correlation in cases of infectious granulomatous dermatitis.
Keywords: Actinomycosis, cutaneous tuberculosis, cysticercosis, granulomatous dermatitis, histoplasmosis, leprosy
How to cite this article:
Singh PJ, Kumar A. Infectious granulomatous dermatitis: Clinicohistopathological study with some unusual clinical presentation. Acta Med Int 2020;7:102-7 |
| Introduction | |  |
Granulomatous inflammation is a distinctive form of chronic inflammation. It is characterized by the formation of granuloma consisting of discrete collection of epithelioid histiocytes admixed with variable numbers of multinucleate giant cells of varying types and other inflammatory cells.[1] Granulomatous dermatitis can be classified according to the type of granuloma present in it which, in turn, is classified according to the arrangement of cells, presence or absence of central necrosis, suppuration, and foreign material or organisms into the following different seven types tuberculoid, sarcoidal, necrobiotic, suppurative, foreign body, xanthogranulomatous, and miscellaneous.[1]
Granulomatous dermatitis has a varied differential diagnosis ranging from infectious etiologies to immunologically mediated diseases. Thus, reporting of these cases becomes a diagnostic challenge for a general histopathologist without any specialized training in dermatopathology.
In tropical countries like India, infectious etiology forms an important cause of granulomatous dermatitis and it should be ruled out in all the cases.[1],[2] Leprosy and tuberculosis (TB) form the most common cause of infectious granulomatous dermatitis.[2],[3] Despite reports of global elimination of leprosy in the year 2000, it still continues to be a social stigma with new cases being reported from different parts of the world.[4],[5] According to the 2016–2017 annual report submitted by the National Leprosy Eradication Program in India, the prevalence rate of leprosy was 0.66 per 10,000 population.[6]
As per the 2017 Global TB report, India accounts for about a quarter of the world's TB cases.[7] Although cutaneous TB accounts for only 1%–2% of all TB cases, in countries with high prevalence, the absolute number of cases becomes significant.[8] Cutaneous TB has a varied clinical presentation depending on the mode of infection and immune response of the host. Previously, cutaneous TB was mainly classified based on its pathophysiology. However, recently, a more widely acceptable method of classification based on the route of propagation and bacterial load is used.[9],[10]
Other causes of infectious granulomatous dermatosis are fungal infections, actinomycosis, and parasitic infestation like leishmaniasis.
The present study was carried out with the aim to determine the frequency of various etiological agents causing infectious granulomatous dermatitis in a tertiary care hospital setup and to see clinicohistopathological correlation in these cases.
| Materials and Methods | | |
Study design and setting
This is a hospital-based retrospective study conducted in the department of pathology, in a tertiary care hospital from North India.
Subjects and methods
A total of 300 skin biopsy cases were retrieved from the histopathology laboratory record section for analysis over a period of 1 year from August 2019 to July 2020. The cases diagnosed as infective granulomatous dermatitis were included in the study. Routine histopathological analysis was done on slides stained with hematoxylin and eosin stain. Special stains such as Ziehl–Neelsen (ZN), Fite Faraco (FF), periodic acid Schiff (PAS), and Gram stain were applied where ever necessary. Relevant clinical data were retrieved from requisition forms.
Statistical analysis
Data analysis was done using Microsoft Excel sheet.
| Results | | |
A total of 40 cases of infectious granulomatous dermatitis were included in the study. Leprosy was the most common etiological factor found in 23 cases (57.5%). Further distribution of cases according to the etiological factors is shown in [Table 1]. Clinicohistopathological correlation was seen in 35/40 cases (87.50%) as shown in [Table 1]. | Table 1: Distribution of infectious granulomatous dermatitis cases according to the etiological factor and their clinical correlation
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Gender-wise distribution showed males were 57.50% (23 cases) and females were 42.5% (17 cases). Both cases of actinomycosis and a single case of cysticercosis occurred in females. Age-wise distribution showed a maximum number of cases in the age group of 41–60 years (13 cases, 32.5%) as shown in [Table 2]. | Table 2: Age group-wise distribution of infectious granulomatous dermatitis
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Leprosy
In the present study, the clinical correlation was seen in all 23 cases of leprosy. On histopathological examination, leprosy cases were subdivided into the groups based on the Ridley and Jopling classification as shown in [Table 3]. Histopathological findings such as involvement or destruction of the nerve by granuloma, lack of fibrosis, absence of caseous necrosis, and associated atrophy of epidermis were used to differentiate cases of tuberculoid leprosy from cutaneous TB as shown in [Figure 1]. One case each of type 1 and type 2 lepra reaction was reported as shown in [Figure 2]. FF stain was positive in 10 cases (43.47%). | Figure 1: Cases of lepromatous leprosy: (a) Diffuse sheets of foamy histiocytes (Virchow's cells) in the dermis and separated from the epidermis by Grenz zone (arrow) (H and E, ×5); (b) Virchow's cells surrounding the nerve fibers (H and E, ×10); (c) Virchow's cells surrounding the nerve fibers (H and E, ×40); (d) Macrophages distended with large groups (globi) of magenta-colored rod-shaped leprosy bacilli (circles) (Fite Faraco stain for acid-fast bacilli, oil immersion, ×100)
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 | F i g u r e 2 : (a and b) Cas e of e r y thema nodosum leprosum: (a) Dermis and subcutaneous tissue show dense inflammatory infiltrate consisting of foamy histiocytes admixed with neutrophils, panniculitis (H and E, ×5); (b) Collection of histiocytes and neutrophils surrounding the dermal appendages (H and E, ×40); (c) Case of Type 1 Lepra reaction shows edema within and surrounding the granuloma and these granulomas are seen encroaching the lower epidermis (H and E, ×40)
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Cutaneous tuberculosis
All the 12 cases of cutaneous TB were correlated clinically. These were further classified based on bacterial load into paucibacillary and multibacillary groups as shown in [Table 4]. Cutaneous TB was differentiated from tuberculoid leprosy by observing associated changes seen in the epidermis like hyperplastic reaction or areas of ulceration, absence of nerve involvement, and significant fibrosis in addition to the presence of tuberculoid granuloma with the occasional area of caseous necrosis [Figure 3]. The maximum number of cases (10, 83.33%) belonged to the paucibacillary group and lupus vulgaris was the most common subtype seen in six cases (50.0%). ZN stain for acid-fast bacilli was positive in three cases of cutaneous TB, i.e., one case each of lupus vulgaris, tubercular ulcer, and tubercular abscess. | Figure 3: Lupus vulgaris: (a) hyperplastic stratified squamous epithelium and multiple epithelioid cell granuloma in the dermis (H and E, ×5); (b) tuberculoid granuloma composed of epithelioid histiocytes, scattered Langhans' type of giant cells, and lymphocytic infiltrate. There is minimal caseation necrosis (H and E, ×40); (c) Ziehl.Neelsen stain for acid.fast bacilli demonstrates magenta-colored rod-shaped bacilli (circle) in the lesion (oil immersion, ×100)
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Actinomycosis
In the present study, two cases (5.0%) of actinomycosis were reported in young females who presented with swelling over the lower limb. In the case of a 15-year-old female, the provisional diagnosis was a sebaceous cyst. In another case of a 22-year-old female, who presented with swelling and discharging sinus, the provisional diagnosis was soft-tissue tumor. Microscopic examination in both the cases revealed suppurative granuloma with purple-colored bacterial colonies/grains showing the Splendore–Hoeppli phenomenon [Figure 4]. The diagnosis of actinomycosis was confirmed by PAS and Gram stain. | Figure 4: (a) Actinomycosis: Suppurative granuloma with purple.colored bacterial colonies showing the Splendore.Hoeppli phenomenon (H and E, ×10). (b) Cysticercosis: The cystic cavity containing scolex of the cysticercus larva surrounded by fibrous tissue and granulomatous inflammation (H and E, ×10). (c) Histoplasmosis: The histiocytes show the presence of round to ovoid bodies surrounded by clear halo (circles) in the cytoplasm (H and E, ×100)
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Parasite
In the present study, one case (2.5%) of cutaneous parasitic infestation was reported in a 10-year-old female who presented with swelling over the eyelid. The provisional diagnosis in this case was a dermal lipoma. On histopathological examination, a cystic cavity containing the irregular membranous structure of a parasite surrounded by fibrous tissue and granulomatous inflammation was observed [Figure 4]. The parasite was identified as cysticercosis based on the characteristic appearance of the scolex of the cysticercus larva.[11]
Fungal infection
In the present study, one case (2.5%) each of dermatophytosis and histoplasmosis was reported. A case of dermatophytosis was reported in a 22-year-old male who presented with a nodular growth in the right axilla. The provisional clinical diagnosis in this case was cutaneous TB. Histopathological examination showed a perifollicular granulomatous inflammation along with fungal hyphae and spores. PAS stain demonstrated fungal hyphae and spores while ZN stain was negative.
A case of histoplasmosis occurred in a 64-year-old male who presented with swelling over the chest and forearm. His clinical diagnosis was an epidermal cyst. Histopathological examination showed a well-circumscribed granulomatous lesion consisting of histiocytes, epithelioid cells, Langhans, and foreign body type of giant cells surrounded by mantle of lymphocytes. The histiocytes showed the presence of round to ovoid bodies surrounded by clear halo in the cytoplasm on routine H and E stained slide [Figure 4]. Further PAS stain revealed magenta-colored round to oval bodies surrounded by a halo. thereby confirming the diagnosis of histoplasmosis.
| Discussion | | |
Various etiological agents such as bacteria, parasites, and fungal infections affecting the skin can cause granulomatous inflammation. Different types of granulomas can be seen in infective granulomatous dermatitis depending on the causative agent and host's immune response. In the present study, we classified infective granulomatous dermatitis cases based on their causative etiological factor.
The present study showed a male predominance with 23 (57.5%), which is in concordance with other studies from India,[12],[13],[14],[15] Southeast Asia,[3],[16] and Egypt,[17] whereas a study from India by Kumbar et al.[18] reported female predominance.
In the present study, the maximum number of cases (32.5%) belonged to the age group of 41–60 years. Studies from India by Potekar et al.[12] and Agrawal et al.[15] reported a maximum number of cases in the younger age group of 21–30 years and 21–40 years, respectively. Studies from other tropical southeast Asian countries found the maximum number of cases in the fourth decade of life.[3],[16]
Leprosy
In the present study, leprosy was the most frequent etiological factor found in 57.50% of cases. By Ridley and Jopling classification, borderline tuberculoid leprosy was the most frequent subtype (7 cases, 30.43%). Similar findings were reported by other studies from India[2],[12],[13],[18] and Nepal.[16] In contrast to our findings, a study from Pakistan[19] reported cutaneous leishmaniasis as the most common form of granulomatous dermatosis and no case of leprosy was reported by them. A study from Egypt[17] reported borderline lepromatous leprosy as the most common subtype.
In the present study, FF stain was positive for lepra bacilli in 43.47% of cases of leprosy. This is in concordance with the study done by Bal et al.,[2] whereas Chakrabarti et al.[13] and Kumbar et al.[18] reported lower percentage of positivity for lepra bacilli.
Tuberculosis
Lupus vulgaris is the most common form of cutaneous TB resulting from hematogenous spread.[20] In the present study too, lupus vulgaris was the most common form of cutaneous TB (6 cases, 50.0%). Similar findings were reported by other studies from India[2],[13],[14],[21] and Egypt.[17] A study from Nepal[16] reported equal number of lupus vulgaris and TB cutis orificialis cases, whereas a study from Brazil[10] reported erythema induratum of Bazin as the most common form of cutaneous TB.
In the present study, cutaneous TB was most frequent in the age group of 0–20 years (5 cases, 41.66%). Similar findings were reported by Kannan et al.[14] and Jayanthi et al.[21] In the present study, the gender-wise distribution of cutaneous TB showed male predominance, which is similar to the other studies from India,[14],[21] whereas Chakrabarti et al.[13] reported female predominance.
In the present study, the most frequent site of lupus vulgaris was the face, which is in concordance with the study from Egypt,[17] whereas Kannan et al.[14] from India reported lower limbs and buttocks as the most common site for lupus vulgaris.
Actinomycosis
In the present study, two cases of primary cutaneous actinomycosis affecting the lower extremities were reported Actinomycosis is a rare chronic suppurative and granulomatous bacterial infection caused by Gram-positive organism belonging to the Actinomyces genus. The most commonly affected sites are the cervicofacial, thoracic, and abdominopelvic regions. It presents with a clinical triad of swelling, sinus tract, and discharging grains. Primary cutaneous actinomycosis of the lower extremities is quite rare and it mainly occurs due to traumatic implantation of the organism on the exposed skin. In the present study, actinomycosis was not suspected in both the cases due to lack of history of trauma and discharging grains. In the present study, both the cases were reported in young females. However, other studies from India reported cases of primary cutaneous actinomycosis in middle-aged patients.[22],[23],[24] In the present study, the incidence of actinomycosis was 5.40%, which is comparable to the previous studies from India,[13],[18] whereas a study from Egypt reported a lower incidence.[17]
Parasite
Cysticercosis is a parasitic infestation caused by Taenia solium larvae. Humans are an accidental intermediate host. It presents as asymptomatic small subcutaneous nodule. It most commonly affects the central nervous system, followed by striated muscles, eyes, and subcutaneous tissue. A review of the literature shows only a few cases of eyelid cysticercosis reported in the past with its incidence being 0.6%.[25],[26],[27] In the present study, a case of eyelid cysticercosis was reported in a young girl. She had no other complaints except for a longstanding painless swelling over the upper eyelid and excision was done for cosmetic reasons. These findings are comparable to the previous studies from India.[26],[27] In the present study, there was no clinical suspicion of cysticercosis due to the absence of any other signs or symptoms. This can occur due to the varied incubation period of cysticercosis. Such longstanding benign eyelid masses are commonly misdiagnosed as dermoid cysts or benign soft-tissue tumors.[25],[26],[27] In the present study, the clinical diagnosis was dermal lipoma. While in other studies, the cases were misdiagnosed as sebaceous or dermoid cysts.[25],[26],[27]
Fungal
Histoplasmosis is a systemic mycosis that can present as cutaneous lesion. It is caused by Histoplasma capsulatum, a dimorphic fungus found in soil. Skin lesions can occur in few cases of disseminated histoplasmosis or rarely as primary cutaneous histoplasmosis. Although it mainly affects immune-compromised individuals, some cases are reported in immune-competent patients.[28] In the present study, a case of primary cutaneous histoplasmosis occurred in an elderly male patient in form of a skin nodule over the upper extremity and trunk. He had no other signs or symptoms, however his immune status was unknown. As opposed to this, previous studies from India by Raina et al.[28] and Nair et al.[29] reported it in a younger immunocompetent patients with a history of nonhealing ulcer over extremities.
Dermatophytosis can be caused by fungi belonging to genera of Trichophyton, Microsporum, or Epidermophyton The major etiological agent for dermatophytic or Majocchi's granuloma is Trichophyton rubrum.[30] Dermatophytic granuloma presents in two forms based on the patient's immune status. In immunocompetent patients, it usually presents as a perifollicular papule over lower extremities, often accompanied by a history of trauma or use of topical steroids. In immunocompromised patients, it can present either in form of nodule or perifollicular pustule, usually involving the upper extremities.[30] In the present study, it presented as a perifollicular nodule in the axilla of a young patient, however his immune status was unknown. The provisional clinical diagnosis in our case was cutaneous TB which is the most common differential diagnosis for dermatophytic granuloma.
| Conclusion | | |
Histopathological examination of skin biopsies is an important diagnostic tool in determining definitive diagnosis and clinicohistopathological correlation of infectious granulomatous dermatitis. In our study, leprosy and cutaneous TB were the most frequent type of infectious granulomatous dermatitis. Although major efforts are being made toward controlling TB and eradicating leprosy through various national programs, these diseases still continue to be a serious public health problem in various parts of India. Some unusual clinical presentation was seen in the rare cases of cysticercosis, actinomycosis, and histoplasmosis causing infectious granulomatous dermatitis.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Weedon D, Strutton G, Rubin A. The granulomatous reaction pattern. In: Weedon's Skin Pathology. 3 rd ed. Edinburgh: Churchill Livingstone/Elsevier; 2010  |
| 2. | Bal A, Mohan H, Dhami GP. Infectious granulomatous dermatitis: A clinico pathological study. Indian J Dermatol 2006;51:217-20. [Full text] |
| 3. | Jayawardhana MP, Gunewardhana RT, Dissanayake M. A histopathological analysis of granulomatous dermatoses – A single centre experience from Sri Lanka. J Diagn Pathol 2016;11:23-8. |
| 4. | World Health Organization. WHO, Regional Office for South East Asia; Guidelines for the diagnosis, treatment and prevention of leprosy. R Chou. New Delhi: World Health Organization; 2018. Available from: http://nlep.nic.in/pdf/WHO%20Guidelines%20for%20leprosy.pdf [Last accessed on 2020 Jan 03]. |
| 5. | World Health Organization. Global Leprosy Strategy 2016–2020: Accelerating Towards a Leprosy-Free World. New Delhi, World Health Organization, Regional Office for South-East Asia; 2016. |
| 6. | Narasimha RP, Suneetha Sujai S. Current situation of leprosy in India and its future implications. 2018; 9(2): 83-89. |
| 7. | |
| 8. | Elder DE, Elenitsas R, Johnson BL, Murphy GE, Xu X. Bacterial diseases. In: Elder DE, editor. Lever's Histopathology of Skin. 11th ed. Philadelphia (PA): Wolters Kluwer Health/Lippincott Williams & Wilkins; 2015. p. 672. |
| 9. | Frankel A, Penrose C, Emer J. Cutaneous tuberculosis: A practical case report and review for the dermatologist. J Clin Aesthet Dermatol 2009;2:19-27. |
| 10. | Spelta K, Diniz LM. Cutaneous tuberculosis: A 26-year retrospective study in an endemic area of tuberculosis, Vitória, Espírito Santo, Brazil. Rev Inst Med Trop Sao Paulo. 2016 Jul 11;58:49. doi: 10.1590/S1678-9946201658049. |
| 11. | Weedon D, Strutton G, Rubin A. Protozoal infection. In: Weedon's Skin Pathology. 3rd ed. Edinburgh: Churchill Livingstone/Elsevier; 2010. p. 646 47. |
| 12. | Potekar RM, Javalgi AP, Rodrigues LD, Dwarampudi RS. Histopathological study of infectious granulomatous skin lesions. 2018;5:A580 84. |
| 13. | Chakrabarti S, Pal S, Biswas BK, Bose K, Pal S, Pathak S, et al. Clinico-pathological study of cutaneous granulomatous lesions-a 5 yr experience in a tertiary care hospital in india. Iran J Pathol 2016;11:54-60. |
| 14. | Kannan R, Chellappan L,Venu S, Chandrasekar M. A retrospective study on clinicopathological correlation of cutaneous tuberculosis Int J Res Dermatol 2018;4:595 9. |
| 15. | Agarwal D, Singh K, Saluja SK, Kundu PR, Kamra H, Agrawal R. Histopathological review of dermatological disorders with a keynote to granulomatous lesions: A retrospective study. Int J Sci Stud 2015;3:66 9. |
| 16. | Gautam K, Pai RR, Bhat S. Granulomatous lesions of the skin. J Pathol Nepal 2011;1:81-6. |
| 17. | El-Khalawany M, Meraag I, Eassa B, El-Naby HH. Clinicopathological features and the practice of diagnosing infectious cutaneous granulomas in Egypt. Int J Infect Dis 2011;15:e620 6. |
| 18. | Kumbar R, Dravid N, Nagappa KG, Rokade C. Infectious granulomatous dermatitis at a tertiary care centre in North Maharashtra: A histopathological study. J Clin Diagn Research. 2016 Nov, Vol-10 (11): EC13-EC16 |
| 19. | Qureshi R, Sheikh RA, Haque AU. Chronic granulomatous inflammatory disorders of skin at a tertiary care hospital in Islamabad. Int J Pathol 2004;2:31 4. |
| 20. | Weedon D, Strutton G, Rubin A. Bacterial and rickettsial infections. In: Weedon's Skin Pathology. 3 rd ed. Edinburgh: Churchill Livingstone/ Elsevier; 2010. p. 557. |
| 21. | Jayanthi NS, Anandan V, Kopika S. Various presentations of cutaneous tuberculosis at a tertiary care centre: A one year prospective study. Int J Res Dermatol 2018;4:559 62. |
| 22. | Sonam S, Rachit S, Sansar CS. Primary cutaneous actinomycosis of the lower extremity: A clinical dilemma. J Orthop Surg Rehabil 2017;1:5-8. |
| 23. | Hossain MI, Khan A. Primary cutaneous actinomycosis of lower extremity: A rare case report. Anwer Khan Modern Med Coll J 2015;6:55-7. |
| 24. | Metgud SC. Primary cutaneous actinomycosis: A rare soft tissue infection. Indian J Med Microbiol 2008;26:184-6. [ PUBMED] [Full text] |
| 25. | Rai PJ, Nair AG, Trivedi MG, Potdar NA, Gopinathan I, Shinde CA, et al. An unusual eyelid mass of cysticercosis: A Twist in the tale. J Cutan Aesthet Surg 2016;9:126-8. [ PUBMED] [Full text] |
| 26. | Bhat A, Narasimha A, Vijaya C. Isolated eye lid Cysticercosis: Report of a rare case with review of literature. J Clin Biomed Sci 2014;4:367-69. |
| 27. | Bhadarge PS, Datar SS, Sonarkhan SD, Pagrut KB, Shrivastava AC, Umap PS. A case of isolated eyelid cysticercosis masquerading as a dermoid cyst: Histopathology to the rescue. Int J Res Med Sci 2016;4:4202-4. |
| 28. | Raina RK, Mahajan V, Sood A, Saurabh S. Primary cutaneous histoplasmosis in an immunocompetent host from a nonendemic area. Indian J Dermatol 2016;61:467. [ PUBMED] [Full text] |
| 29. | Nair SP, Vijayadharan M, Vincent M. Primaty cutaneous histoplasmosis. Indian J Dermatol Venereol Leprol 2000;66:151-3. [ PUBMED] [Full text] |
| 30. | Boral H, Durdu M, Ilkit M. Majocchi's granuloma: Current perspectives. Infect Drug Resist 2018;11:751-60. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]
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