Correspondence e59
Figure 1 (a, b) A tumor on the right
frontotemporal region of the scalp. Note the
central ulceration, serpiginous margins, and
a verrucous surface of the tumor
Figure 2 Histology shows a proliferation of well differentiated
squamous epithelial cells. The tumor demonstrates a broad pushing
margin extending into the dermis (Hematoxylin and eosin stain,
9200)
Figure 3 Low-power micrograph showing a proliferation of well-
differentiated squamous cells. Note the pushing margin which is
extending into the dermis (Hematoxylin and eosin, 9100)
ª 2022 the International Society of Dermatology.
Jacob S. Sons*, MBChB (UKZN)
Antoinette V. Chateau, BSc, MBChB, DCH, FC Derm (SA), MMedSci
Department of Dermatology, Greys Hospital, Nelson
R Mandela School of Medicine, University of KwaZulu- Natal,
Durban, South Africa
*E-mail: sons.jacob@gmail.com
Conflict of interest: None.
Funding source: None.
doi: 10.1111/ijd.16518
References
1 Pattee SF, Bordeaux J, Mahalingam M, Nitzan YB, Maloney ME.
Verrucous carcinoma of the scalp. J Am Acad Dermatol. 2007;56
(3):506–7.
2 Murao K, Kubo Y, Fukumoto D, Matsumoto K, Arase S.
Verrucous carcinoma of the scalp associated with human
papillomavirus type 33. Dermatol Surg. 2005;31(10):1363–5.
3 Krishnamurthy A, Ramshankar V, Soundara TV, Majhi U. Multiple
synchronous verrucous carcinomas of the scalp in the
background of generalized verruca vulgaris. Indian J Dermatol.
2015;60(2):182–4.
4 Del Pino M, Bleeker MC, Quint WG, Snijders PJ, Meijer CJ,
Steenbergen RD. Comprehensive analysis of human
papillomavirus prevalence and the potential role of low-risk
types in verrucous carcinoma. Mod Pathol. 2012;25(10):
1354–63.
5 Hannah CE, Weig EA, Collier S, Stone MS, Juma O, Mcharo JJ,
et al. Verrucous carcinoma: An unexpected finding arising from a
burn scar. JAAD Case Rep. 2019;5(3):225–7.
Diagnostic difficulties in secondary syphilis: a
case report
Dear Editor,
A 25-year-old Japanese man was referred to our hospital due
to fever, joint pain in the knees, ankles, shoulders, elbows, and
wrists, and scaly erythema on the trunk and extremities. The
International Journal of Dermatology 2023, 62, e54–e104

e60 Correspondence
patient first experienced right knee pain 3 weeks prior to the ini-
tial visit. Additional joint pain, exanthema, and fever followed,
for which analgesics were prescribed at a local clinic. Physical
examination revealed well-defined, violaceous, and scaly ery-
thema on his trunk and extremities (Fig. 1a,b). No palmoplantar,
mucosal, or genital lesions were observed (Fig. 1c). The patient
had no underlying diseases. From the clinical manifestations,
differential diagnoses included guttate psoriasis, psoriatic arthri-
tis (PsA), and pityriasis lichenoides chronica (PLC). Routine
tests before skin biopsy showed positive results of rapid plasma
antigen reagin test (RPR, 125 RPR Unit [RU] [normal, 0 RU])
and Treponema pallidum (TP) antibody test (8515 titer unit [TU]
[normal, 0 TU]). Screening tests for other sexually transmitted
infections, including human immunodeficiency virus; hepatitis A,
B, and C virus; gonorrhea; and chlamydia were negative.
Histopathological findings from the scaly erythema on the abdo-
men revealed hyperkeratosis with parakeratosis, acanthosis,
and lymphocytic infiltration in the epidermis; vacuolar degenera-
tion of the basal stratum; and dense band-like inflammatory infil-
tration of lymphocytes, histiocytes, and plasma cells in the
upper dermis (Fig. 1d,e). Immunohistochemical analysis
revealed TP proliferation in the epidermis and upper dermis
(Fig. 1f). A diagnosis of secondary syphilis was made. An
International Journal of Dermatology 2023, 62, e54–e104
13654632, 2023, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/ijd.16238 by UFF - Universidade Federal Fluminense, Wiley Online Library on [27/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
additional interview revealed that he lived with a male sexual
partner. Through the patient, the partner was informed of the
diagnosis and told to see a doctor. In Japan, intramuscular ben-
zathine penicillin was not available at that time. The patient was
treated with amoxicillin (1500 mg/day) and probenecid
(750 mg/day) for 2 weeks. The symptoms improved, and the
cutaneous lesions healed with postinflammatory hyperpigmenta-
tion. Along with clinical improvement, the RPR declined to 36
RU, which indicated successful treatment.
Secondary syphilis is caused by hematogenous dissemina-
tion of TP.1 Clinical manifestations are extraordinarily variable
and closely resemble other diseases.1 In this case, the differen-
tial diagnosis included inflammatory skin diseases such as gut-
tate psoriasis triggered by infections, PsA, and PLC. Indications
for a differential diagnosis are as follows: in psoriasis, erythema,
silvery scales, and petechiae detected using dermoscopy. Con-
versely, psoriasiform lesions in secondary syphilis can be
described as orange, pink, or violaceous macules.2 They are
predominantly observed on the palms and soles.3 In PsA,
arthralgia is characterized by peripheral arthritis, spondyloarthri-
tis, enthesitis, and dactylitis.4 In PLC, systemic symptoms rarely
occur; however, erythematous macules and papules may
develop with a reddish-brown hue and a centrally adherent
Figure 1 (a) Well-defined, violaceous, and
scaly erythema on the trunk and upper
extremities. (b) Well-defined, violaceous,
and scaly erythema on the back. (c) No
palmoplantar lesions observed. (d)
Histopathology showing acanthosis, dense
band-like inflammatory infiltration in the
upper dermis, and inflammatory infiltration
around the small vessels in the upper and
mid-dermis (Hematoxylin and eosin, 940).
(e) Histopathology showing hyperkeratosis
with parakeratosis, acanthosis, and
lymphocyte infiltration in the epidermis;
vacuolar degeneration of basal stratum; and
dense band-like inflammatory infiltration of
lymphocytes, histiocytes, and plasma cells
in the upper dermis (Hematoxylin and eosin,
9200). (f) Immunohistochemistry showing
Treponema pallidum proliferation in the
epidermis and upper dermis (Treponema
pallidum antibody, 9400)
ª 2022 the International Society of Dermatology.

scale that can be detached, revealing a shiny, pinkish-brown
surface.5 In some cases, these findings can be helpful to sus-
pect syphilis. However, syphilis is a great pretender and should
always be considered a part of the differential diagnosis of a
pleomorphic rash. The only way not to miss syphilis is to per-
form routine syphilis tests on all patients. Even if it is negative,
there is a possibility of the prozone phenomenon, and repeating
the test should be considered.
Okuto Iwasawa, MD
Koji Kamiya*, MD, PhD
Hirofumi Okada, MD
Takeo Maekawa, MD, PhD
Mayumi Komine, MD, PhD
Mamitaro Ohtsuki, MD, PhD
Department of Dermatology, Jichi Medical University,
Shimotsuke, Japan
*E-mail: m01023kk@jichi.ac.jp
Conflict of interest: None.
Funding source: None.
doi: 10.1111/ijd.16238
References
1 Hook EW 3rd. Syphilis. Lancet 2017; 389: 1550–1557.
2 Griffiths CEM, Armstrong AW, Gudjonsson JE, et al. Psoriasis.
Lancet 2021; 397: 1301–1315.
3 Baughn RE, Musher DM. Secondary syphilitic lesions. Clin
Microbiol Rev 2005; 18: 205–216.
4 Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl
J Med 2017; 376: 957–970.
5 Bowers S, Warshaw EM. Pityriasis lichenoides and its subtypes.
J Am Acad Dermatol 2006; 55: 557–572. quiz 73–76.
Assessment of alopecia areata universalis successfully
treated with upadacitinib
Dear Editor,
We describe the case of a 25-year-old man with a 4-year his-
tory of alopecia areata universalis (AAU) that had been previ-
ously treated with topical diphencyprone and systemic agents
(intramuscular triamcinolone, oral cyclosporine, and methotrex-
ate) without clinical benefit. Physical examination showed hair
loss on the entire body with a Severity of Alopecia Tool (SALT)
score of 100 (Figure 1a). The patient denied any personal or
family history of autoimmune or atopic conditions. Laboratory
examinations (blood cell count and thyroid, liver, and renal func-
tion) resulted within normal limits. Because of the lack of
response to previous treatments, systemic therapy with upadac-
itinib, a Janus Kinase (JAK)-1 selective inhibitor,1 was started
off-label at the dosage of 30 mg/daily.
ª 2022 the International Society of Dermatology.
13654632, 2023, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/ijd.16238 by UFF - Universidade Federal Fluminense, Wiley Online Library on [27/07/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Correspondence e61
Dermoscopy and line-field confocal optical coherence tomog-
raphy (LC-OCT) were performed to assess the subclinical fea-
tures of the disease at baseline and during treatment. LC-OCT
is an in vivo diagnostic tool combining physical principles of
OCT and reflectance confocal microscopy (RCM). It provides
vertical (similar to OCT up to 500 lm depth) and horizontal
imaging acquisition (comparable with RCM, 1.3-lm lateral reso-
lution, and 1.1-lm axial resolution) as well as 3D stacks for a
three-dimensional reconstruction, within a visual field of
1.2 mm 9 0.5 mm.2 Upon dermoscopy, yellow dots, black dots,
and exclamation mark hairs were seen at baseline on the vertex
(Figure 1d). By means of LC-OCT, yellow dots were recognized
as cone-shaped structures filled with bright material in vertical
sections (Figure 2a). After 4 weeks of upadacitinib therapy, no
remarkable changes of AAU were clinically evident (SALT
score: 85) (Figure 1b), whereas dermoscopy showed the pres-
ence of sporadic vellus hairs (Figure 1e), and LC-OCT detected
both numerous hairs originating from the same follicular opening
(doublets), indicating hair regrowth, and residual signs of dis-
ease activity (Figure 2b,c). Indeed, yellow dots and black dots,
respectively, appearing as empty lumina with a collection of
bright material and dark structures with remnants of dysmorphic
hairs in horizontal sections, were still detected over the entire
scalp (Figure 2c). At week 12, an almost complete clinical/tri-
choscopic hair regrowth involving the scalp, beard area, eye-
brows, and eyelashes was noticed (SALT score: 9) (Figure 1c,
f). No adverse events were detected during treatment with
upadacitinib.
In our patient, upadacitinib was prescribed exclusively for
the treatment of AA, conversely to other cases reporting its
efficacy in the management of atopic dermatitis, with beneficial
effects on concomitant AA.3,4 Non-invasive assessment
through dermoscopy and LC-OCT was useful to evaluate hair
regrowth and the persistence of simultaneous signs of disease
activity that resulted more evident upon LC-OCT. Indeed, LC-
OCT detected the presence of yellow dots and black dots at
week 4, with a diffuse distribution, beyond revealing vellus
hairs that are also observed at the dermoscopic examination.
Thus, LC-OCT may improve the non-invasive assessment of
AA, revealing microscopic aspects on the effective status of
disease activity also during a treatment, potentiating the der-
moscopic evaluation. We proposed upadacitinib because of
the key role of IFN-c and other upregulated cytokines (i.e., IL-
2 and IL-15) in the pathogenesis of AA, which signal through
JAK-1.5
In conclusion, this report contributed to the growing use of
upadacitinib for the treatment of AA, providing further insights
on the use of LC-OCT as a beneficial tool for the early detection
of microscopic changes indicative of disease activity and drug
response. Further larger datasets are needed to corroborate our
findings.
International Journal of Dermatology 2023, 62, e54–e104