Pathology Outlines

Skin nontumor
Infectious disorders
Syphilis

Author: Silvija P. Gottesman, M.D.

Editor-in-Chief: Debra Zynger, M.D.

Topic Completed: 24 March 2020

Revised: 24 March 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: Syphilis[TI] skin[TI] full text[sb]

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Table of Contents

Cite this page: Gottesman SP. Syphilis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/skinnontumorsyphilis.html. Accessed April 3rd, 2020.

Definition / general

Syphilis is primarily a sexually transmitted disease
Clinically, in the secondary stage, presents with a papulosquamous eruption and has many histologic mimickers, including psoriasis

Essential features

Lichenoid superficial and deep perivascular and periadnexal lymphohistiocytic inflammation with admixed plasma cells
Up to 33% of biopsies may lack plasma cells
Immunohistochemistry is more sensitive than silver stains

Terminology

Lues venerea, Cupid's disease

ICD coding

ICD-10: A51.39 - other secondary syphilis of the skin

Epidemiology

Transmitted via sexual contact
Can also be transmitted congenitally and rarely via blood products
More prevalent in men than in women, especially ages 20 - 29
Higher incidence in gay and bisexual men (MMWR Morb Mortal Wkly Rep 2014;63:402)

Sites

Skin, mucosal surfaces, eyes, brain / nerves, blood vessels, bones, joints and liver (CDC: Syphilis [Accessed 11 December 2019])

Pathophysiology

On skin to skin contact, it enters via areas of microtrauma, multiplies locally and disseminates systemically within 24 hours (Infect Dis Clin North Am 2013;27:705)

Etiology

Treponema pallidum, highly motile coiled spirochete

Clinical features

Primary syphilis: painless chancre with nontender lymphadenopathy 1 - 3 weeks after exposure
Secondary syphilis:
- Papulosquamous thin papules on the trunk and extremities, palms and soles, fever and adenopathy
- Rash may resemble a drug eruption, pityriasis rosea and psoriasis
- May present as moth eaten alopecia on the scalp, mucous patches on tongue
Tertiary syphilis: may present with gummatous lesions, neurologic or cardiovascular symptoms (Infect Dis Clin North Am 2013;27:705)

Diagnosis

T. pallidum can be visualized using darkfield microscopy
Blood and cerebrospinal fluid (CSF) analysis
Skin biopsy for H&E, special stain and immunohistochemical analysis (Infect Dis Clin North Am 2013;27:705)

Laboratory

Nontreponemal and treponemal tests are performed on blood serum
- Nontreponemal tests: rapid plasma reagin (RPR) test or venereal disease research laboratory (VDRL) test
- Treponemal tests: Treponema pallidum particle agglutination assay (TPPA) or fluorescent treponemal antibody absorption (FTA-ABS) test
Cerebrospinal fluid (CSF) analysis
- Lymphocytic pleocytosis and elevated cerebrospinal fluid total protein
- Cerebrospinal fluid venereal disease research laboratory test confirms diagnosis of neurosyphilis
- Of note, cerebrospinal fluid fluorescent treponemal antibody absorption test has a high false positive rate but is more sensitive than cerebrospinal fluid venereal disease research laboratory test

Prognostic factors

Favorable with early treatment

Case reports

27 year old man presents with recurrent oral ulcers (J Indian Acad Oral Med Radiol 2014;26:436)
Man in his late 20s presented with a rash and multiple lytic lesions of the bones (BMJ Case Rep 2014 Sep 19;2014)
36 year old man with progressive vision loss (Case Rep Infect Dis 2014;2014:352047)
39 year old man presents with generalized weakness, joint aches (Cleve Clin J Med 2017;84:510)
59 year old man presents with ulcer of the hard palate (J Med Case Rep 2019;13:227)

Treatment

Penicillin is the main drug of choice
If a pregnant patient with syphilis is allergic to penicillin, an attempt should be made on penicillin desensitization with an allergist
Other medications for nonpregnant adults are doxycycline, tetracycline and ceftriaxone (Infect Dis Clin North Am 2013;27:705, CDC: Syphilis [Accessed 11 December 2019])

Clinical images

Contributed by Mark R. Wick, M.D.

Secondary

Gumma

Microscopic (histologic) description

Primary syphilis: ulcer with lymphoplasmacytic inflammation
Secondary syphilis:
- Lichenoid superficial and deep perivascular and periadnexal lymphohistiocytic inflammation with admixed plasma cells
- Plasma cells may be absent in 33% of biopsies
- Eosinophils can be present
- Marked endothelial swelling and proliferation of blood vessels can be seen
- Commonly identified are vacuolar interface change, acanthosis or lymphocyte exocytosis
- In late secondary syphilis, granulomatous inflammation may be present
- Microabscess formation of the hair follicle has also been seen
- Condyloma lata (lesions on genital skin) show marked epidermal hyperplasia and inflammatory infiltrate akin to secondary syphilis
Tertiary syphilis: large areas of necrosis with peripheral mixed inflammatory infiltrate and Langerhans giant cells
References: J Cutan Pathol 2004;31:595, J Am Acad Dermatol 2015;73:1025, J Am Acad Dermatol 2020;82:156

Microscopic (histologic) images

Contributed by Silvija P. Gottesman, M.D.

Dense lymphohistiocytic inflammation

Plasma cells

Psoriasiform hyperplasia

Secondary syphilis

Treponema IHC

Contributed by
Hillary Rose Elwood, M.D.

Dense plasma cell infiltrate

Contributed by
Mark R. Wick, M.D.

Steiner stain, secondary

Virtual slides

Images hosted on other servers:

Secondary syphilis on acral skin

Positive stains

Silver stains: Warthin-Starry or Steiner stain (41% sensitive) (J Cutan Pathol 2004;31:595)
Immunohistochemical stain: treponema (71% sensitive) (J Cutan Pathol 2004;31:595)

Negative stains

Not relevant to the diagnosis

Molecular / cytogenetics description

PCR based techniques can be used on tissue

Sample pathology report

Skin, punch biopsy:
- Psoriasiform lymphohistiocytic inflammation with plasma cells (see comment)
- Comment: There is psoriasiform epidermal hyperplasia with superficial and deep perivascular lymphohistiocytic infiltrate. Admixed plasma cells are also noted. The infiltrate forms a band beneath the hyperplastic epidermis and envelopes some of the adnexal structures. Endothelial swelling of the superficial vascular plexus is present. A treponemal immunohistochemical stain shows numerous coiled spirochetes in the lower half of the epidermis. These findings are diagnostic of syphilis.

Differential diagnosis

Pityriasis lichenoides et varioliformis acuta:
- Differentiation on histologic grounds is difficult as some cases may also have plasma cells
- Treponema-, silver-
Pityriasis rosea:
- Similar clinically
- Basilar spongiosis and extravasated red blood cells are more likely
- Neutrophils in the stratum corneum are less common
Mycosis fungoides:
- Papillary dermal fibrosis and complete vacuolar changes are more often seen
- While late lesions may have plasma cells, they are rarely seen in early lesions
Alopecia areata:
- Also can show peribulbar lymphocytic inflammation
- Peribulbar plasma cells will not be present

Board review style question #1

A 28 year old man presents with fever, sore throat, lymphadenopathy and a skin rash. Which of the following is the most important cutaneous finding that should prompt suspicion of syphilis?

Erythematous scaly papules on the palms and soles
Genital mucocutaneous ulceration
Maculopapular eruption on the trunk and extremities
Mucosal patches on the bilateral oral commissures

Board review answer #1

A. Erythematous scaly papules on the palms and soles

Comment Here

Reference: Syphilis

Board review style question #2

A punch biopsy specimen from a 26 year old woman with a rash shows a superficial and deep perivascular and periadnexal lymphocytic inflammation. The presence of which of the following should prompt the pathologist to order treponemal immunohistochemical stain?

Histiocytes
Mucin
Neutrophils
Plasma cells

Board review answer #2

D. Plasma cells

Comment Here

Reference: Syphilis