A Case Report: Classical Clinical Presentation of Scrofuloderma

Confirmed with Novel Laboratory Workups

Riris Asti Respati

, Rahmiati

, Teffy Nuari

, Rahadi Rihatmadja

, Eliza Miranda

Sri Linuwih Menaldi

Department of Dermatology and Venereology Faculty of Medicine Universitas Indonesia/

Dr. Cipto Mangunkusumo National Central General Hospital, Indonesia

Department of Anatomical Pathology Faculty of Medicine Universitas Indonesia/

Dr. Cipto Mangunkusumo National Central General Hospital, Indonesia

Keywords: Histopathology, IGRA, scrofuloderma, lymphadenitis, Xpert MTB/RIF

Abstract: Scrofuloderma, can develop on the skin through direct extension from an endogenous source of tuberculosis

such as lymph node. This report presents a case of scrofuloderma in its classical presentation in a 41-year-

old man, who suffered from a three-week history of a painless swelling that ulcerated. Physical examination

revealed two tender nodules on the left anterior neck and armpit. The diagnosis was confirmed bythe

presence of an underlying focus of infection tuberculous lymphadenitis, positive results ofMycobacterium

tuberculosis interferon-gamma release assay (IGRA), Xpert MTB/RIF, and histopathological examination.

Treatment with anti-tuberculosis regiment resulted in an excellent outcome.

1 INTRODUCTION

Cutaneous tuberculosis is a chronic infection of the

skin by Mycobacterium tuberculosis, and less

commonly by M. bovis and M. atypical. (Santos JB et

al., 2014). It is relatively rare and accounts for 1% of

extrapulmonary tuberculosis. In the Asian

community, most cases are between the ages of 10

and 50 years. (Ho SCK, 2003). Scrofuloderma, also

known as tuberculosis cutis colliquative, is a

common form of cutaneous tuberculosis followed by

other formse.g., tuberculosis verrucosa cutis and

lupus vulgaris(Sethi et al., 2012; Haase O et al.,

2014).

The development of clinical manifestations in

scrofuloderma should be understood as the result of

interactions among the environment, agent, and host.

(Santos JB et al., 2014).It most commonly occurs in

the neck from underlying tuberculosis in a deeper

structure, usually a lymph node, bone, and joint.

Starting with lymphadenitis, lymph node attachment

with surrounding tissue causes peri adenitis, which

becomes doughy and progresses to liquefaction.A

cold abscess is formed, and the skin erodes to form a

discharging sinus and fistula formation. The fistula

estuary extends and forms an ulcer. It is

characterized by elongated, irregularly shaped,

granulated tissue at the base, and covered with

seropurulent discharge.The ulcer may be healed with

scarring (Santos JB et al., 2014; Sethi et al.,

2012;Lai-Cheong JE et al.,2007).

Diagnostic steps usually begin with history

taking, physical examination, and confirmation tests,

e.g., polymerase chain reaction, tissue culture,

tuberculin skin test, and histopathology.

2,6

Treatment

of scrofuloderma is similar to pulmonary

tuberculosis. World Health Organization (WHO)

recommends regimens consisted of four drugs,

isoniazid (H), rifampicin (R), pyrazinamide (Z) and

ethambutol (E) given to intensive and continuation

phases.(Ho SCK, 2003;Kar S et al., 2011).

The following report showcases several

techniques, some with their shortcomings, that may

be utilized to improve the accuracy of diagnosis in a

clinically characteristic presentation of scrofuloderma.

2 CASE

A 41-year-old man presented with a three-week

history of multiple ulcerson the upper chest and neck

(Figure 1).It started from a painless neck masses six

Respati, R., Rahmiati, ., Nuari, T., Rihatmadja, R., Miranda, E. and Menaldi, S.

A Case Report: Classical Clinical Presentation of Scrofuloderma Conﬁrmed with Novel Laboratory Workups.

DOI: 10.5220/0009987302990302

In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 299-302

ISBN: 978-989-758-469-5

299

months before a consultation, that gradually

increased in number and size. They suppurated and

broke down, forming ulcers with granulating tissue.

There was no other trauma.

Systemic examination did not reveal drenching

night sweats and unexplained pyrexia. Nonetheless,

approximately2 kilograms of weight loss in the last

two months was admitted. He had neither significant

childhood lung disease or tuberculosis background

and had received BCG vaccination.

Physical examination from the upper chest and

bilateral supraclavicular skin revealed multiple

ulcers measured approximately 4x3 cm, with

suppuration and granulation tissue at the base and

deeply undermined edges.

Routine laboratory work-ups were unremarkable

except for an elevated erythrocyte sedimentation rate

(ESR) 25 mm/hr. Mycobacterium tuberculosis

interferon-gamma release assay (IGRA)was positive

(1.61 IU/mL). Histopathological examination

showed epithelioid granulomas with a variable

number of Langhans giant cell and lymphocytes

(Figure 2)

On a subsequent visit, there were newtwo fixed

tender swelling in the left anterior neck and left

axillary (Figure 3). Physical examination showed

multiple nodular swelling measuring approximately

4x3 cm and 3x3 cm, fixated, doughy, without signs

of acute inflammation. The patient was consulted to

pulmonology division.

Further investigations had been carried out, such

as fine-needle aspiration biopsy (FNAB). The result

showed abscess material with lymphocytes,

histiocyte, neutrophil, with marked caseation

necrosis area. Mycobacterium tuberculosis was

detected using the Xpert MTB/RIF. Chest x-ray was

normal. Another workup, including polymerase

chain reaction (PCR) for Mycobacterium

tuberculosis, mycobacterial culture, Mycobacterium

other than tuberculosis culture, sputum culture, and

tuberculin skin test showed negative findings.

Furthermore, the patient started standard anti-

tuberculosis treatment consisting of four drugs,

rifampicin, isoniazid, pyrazinamide, and ethambutol.

After two months of therapy with anti-tuberculosis

regiments, he reported improved symptoms. No new

nodules had evolved (Figure 4).

Figure1. An ulcerated lesion with purulent fistulain the clavicular region.

Figure 2. Epithelioid granulomas, 100x (A), 400x (B) (hematoxyllin-eosin)

A

ICTROMI 2019 - The 2nd International Conference on Tropical Medicine and Infectious Disease

300

Figure 3. Cervical and axillary tender fixed masses

Figure 4. Lymphadenopathy has improved after two months of treatment.

3 DISCUSSION

Scrofuloderma is increasingly recognized as the

most common form of cutaneous tuberculosis in

adults (Pasmayathy L et al., 2008). This patient was

41 years old, included inthe profoundly affected

population who often have scrofuloderma. The

presentation of cutaneous tuberculosis depends on

the pathogenicity of the mycobacteria, route of

infection, and the level of host cell-mediated

immunity (CMI). Scrofuloderma lesions begin as

subcutaneous nodules which become doughy and

progressive liquefaction.(Santos JB et al., 2014;Ho

SCK,2003;Frankel A et al., 2009).The fistula estuary

extends and forms an ulcer. It is characterized by

suppuration and granulation tissue at the base and

deeply undermined edges.

In our case, they started

as painless swelling overlying his upper chest and

neck six months ago. The masses gradually enlarged

into cold abscess formation. It suppurates and breaks

down, forming an ulcer with granulation tissue at the

base covered with purulent discharge.

Scrofuloderma is caused by dormant tuberculosis

reactivation. There is contiguous involvement of

overlying skin from the underlying focus infection

such as tuberculous lymphadenitis. Scrofuloderma

from tuberculous lymphadenitis often affects the

neck, axillae, chest wall, and groin. (Ho SCK, 2003;

Aliaagaoglu et al., 2015). As can be seen in the

present case, the area of predilection was the neck

and axillae, which were the familiar site of

scrofuloderma. Moreover, there were two tender

swellings occurred in the left supraclavicular and

axillary region, which were tuberculosis

lymphadenitis. The left supraclavicular and axillary

nodes receive lymphatic drainage from the thoracic

duct causing of a lesion at multiple sites. In

scrofuloderma, the host has moderate cell-mediated

immunity. Following infection, macrophages that

circulate to lymph nodes and then haematogenic

spread to other parts of the body phagocyte the

mycobacteria. (Santos JB et al., 2014). Macrophages

act as antigen-presenting cells and interact with T

lymphocyte. (Ho SCK, 2003). When the

mycobacteria survive, in which they divide within

the macrophages. It is inducing the production of

cytokines such as IL-6, IL-12, IL-1α, and IL-1β,

resulting in the recruitment of monocytes,

lymphocytes, neutrophils, and dendritic cells.

The

persistent presence of these interleukins stimulating

macrophages will ultimately lead to their

differentiation into epithelioid and giant cells, which

will be more or less organized into granulomas

A Case Report: Classical Clinical Presentation of Scrofuloderma Conﬁrmed with Novel Laboratory Workups

301

according to individual host factors. (Santos JB et

al., 2014) This explains the histopathology finding

that may show marked caseation necrosis and

abscess material with mixed inflammatory

infiltrations dominate the center of the lesion. (Santo

s JB et al., 2014.Besides, a presence of characteristic

tubercular granulomas with epithelioid cells in the

dermis is observed in 57%–96% of the samples.

(Rahman et al., 2018) showed only 16.7% cases

whereas granuloma with caseous necrosis found in

the dermis. On the other hand, 55.6% the majority of

the cases showed granuloma without caseous

necrosis.

Although not typical, a histopathological

examination from skin showed the presence of

epithelioid cell granulomas with a variable number

of Langhans giant cell and lymphocytes infiltrates in

the dermis. Central caseation necrosis was found

from FNAB, therefore support the diagnosis of

tuberculosis lymphadenitis. Some acid-fast bacilli

can be found (Ho SCK, 2003). This patient’s

bacteriological examination showed no acid-fast

bacilli. This is in line with the literature which stated

that bacteriological examination did not always find

acid-fast bacilli although a higher bacterial load. (Ho

SCK, 2003). Mycobacterial culture is the gold

standard for determining the presence of active TB

infection. (Ho SCK, 2003). However it is not always

possible to obtain a positive result. Positivity is

lower in an exclusively cutaneous presentation, that

is around 23% (Santos JB et al., 2014; Frankel A et

al., 2009).Polymerase chain reaction is used

primarily as a complement to clinicopathological

evaluation. It was reported in another study that one

out of three scrofuloderma patients had a positive

PCR finding(Santos JB et al., 2014;Tan WP et al.,

2007). Positive PCR result is not always obtained. In

the diagnosis of cutaneous TB, the sensitivity and

specificity of PCR vary greatly from literature.

Detection of Mycobacterium tuberculosisby a PCR

in this patient turned out to be negative.

A diagnosis of tuberculous lymphadenitis with a

cutaneous extension (scrofuloderma) has been

made.It was confirmed by history taking, clinical

features, a positive result on IGRA, Xpert MTB/RIF,

and histopathological findings. The patient was

quickly started on an anti-tubercular treatment

regimen that included isoniazid, rifampicin,

ethambutol, and pyrazinamide. The cutaneous lesion

regressed, and the ulcer starts healing.

4 CONCLUSION

In this patient, scrofuloderma occurs as a result of

extension from underlying tuberculous

lymphadenitis. By proper history taking and

morphologic features examination, a preliminary

diagnosis can be made, that must be followed by the

best methods available. Here our case had shown

that although mycobacterial culture and PCR test

failed to yield positive findings, IGRA, Xpert

MTB/RIF, and histopathological evaluations

provided the conclusive results. That the patient

responded well to treatment was another proof of the

infection.

REFERENCES

Santos JB, Figueiredo AR, Ferraz CE, Oliveira MH, Silva

PG, Medeiros VL. Cutaneous tuberculosis:

epidemiologic etiopathogenic and clinical aspects –

Part I. An Bras Dermatol. 2014;89(2): 219–29.

Ho SCK, Cutaneous tuberculosis: clinical features,

diagnosis, and management. H K Dermatol Venereol

Bull. 2003;11:130–8.

Sethi A. Tuberculosis and infections with atypical

mycobacteria. In: Goldsmith LA, Katz Si, Gilchrest

BA, Paller AS, Leffel DJ, Wolff K. Fitzpatrick’s

Dermatology in general medicine. 8th ed. New York:

McGraw-Hill. 2012: p.2225–40.

Haase O, Von Thomsen AJ, Zillikens D, Solbach W,

Kahle B. Recurrent abscesses of the neck:

scrofuloderma. JAMA Dermatol. 2014;150(8):909–10.

Lai-Cheong JE, Perez A, Tang V, Martinez A, Hill V,

Menage HP. Cutaneous manifestations of tuberculosis.

Clin Exp Dermatol. 2007;32(4):461–6.

Santos JB, Figueiredo AR, Ferraz CE, Oliveira MH, Silva

PG, Medeiros VL. Cutaneous tuberculosis: diagnosis,

histopathology and treatment - Part II. An Bras

Dermatol. 2014;89(4): 545–55.

Kar S, Krishnan A, Gangane N, Preetha K.

Scrofuloderma-a case series from rural India. Indian J

Tuberc. 2011;58(4):189–95.

Pandmavathy L, Lakshmana R, Ethirajan N, Manohar U,

Krishnaswamy BK. Scrofuloderma: a

clinicopathological and epidemiological study. Indian

J Dermatol Venereol Leprol. 2008;74(6):700.

Frankel A, Penrose C, Emer J. Cutaneous tuberculosis: a

practical case report and review for the dermatologist.

J Clin Aesthet Dermatol. 2009;2(10):19–27.

Aliaagaoglu C, Atasoy M, Albayrak H, Ozdemir S, Yanik

ME, Aktas A. Scrofuloderma: 30 years of experience

from eastern Turkey. Int J Dermatol. 2015;54(5):612–

Tan WP, Tang MB, Tan HH. Scrofuloderma from the

acromioclavicular joint presenting as a chronic ulcer in

an immunocompetent host. Singapore Med J.

2007;48(9):243–5.

Rahman MA, Asaduzzaman ATM, Mahmud MM,

Chowdhury AM, Rahman MM, Haque MA, et al. Role

of polymerase chain reaction in the diagnosis of

cutaneous tuberculosis. J Pac Assoc Dermatol.

2018;28(3):277–83.

ICTROMI 2019 - The 2nd International Conference on Tropical Medicine and Infectious Disease

302