ACTAS Dermo-Sifiliográficas 112 (2021) 463---483

CASE AND RESEARCH LETTERS

Successful Treatment of White cally asymptomatic, treatment of WSN is focused on
improving the aesthetics and texture of the mucosa.1
Sponge Nevus with Oral Given the low prevalence of this condition, descrip-
Doxycycline: A Case Report and tion of the available therapeutic options is limited
Review of the Literature夽 to isolated clinical case reports and short cases
series.
Tratamiento del nevus blanco esponjoso. A 46-year-old male non-smoker with no relevant personal
Aportación de un caso con respuesta a history was seen for oral lesions that had been present since
childhood. Clinical examination revealed bilateral, whitish,
doxiciclina oral y revisión de la literatura soft plaques that were located on the buccal mucosa and
the lateral aspects of the tongue and remained adhered
To the Editor:
after scraping (Fig. 1A and B). The patient had no similar
lesions in other locations and reported no relevant family
White sponge nevus (WSN) is a rare and benign dis-
history. Although the lesions were asymptomatic, they had
ease that usually affects the oral mucosa and manifests
a significant aesthetic impact on the patient. A biopsy of
as white spongy plaques. Because it is usually clini-

Figure 1 Wrinkled, whitish lesions on the sides of the tongue (A) and on the buccal mucosa (B). Clinical improvement of the
lesions on the side of the tongue (C) and on the buccal mucosa (D) after treatment with oral doxycycline.

夽 Please cite this article as: Amores-Martín E, Melé-Ninot G,

Del Alcázar Viladomiu E, Fernández-Figueras MT. Tratamiento del

nevus blanco esponjoso. Aportación de un caso con respuesta a
doxiciclina oral y revisión de la literatura. Actas Dermosifiliogr.
2021;112:463---466.
 Table 1 Published Cases of White Sponge Nevus: Therapeutic Guidelines, Clinical Responses, and Recurrences
Authors Sex Age Family Treatment Response Recurrence/ Maintenance
History Therapy
Otobe et al.3 F 23 Yes Tetracycline rinses (0.25%, 5 mL for 1 min) 2 times per day for Partial No
12 weeks
F 27 Yes Tetracycline rinses (0.25%, 5 mL for 1 min) 2 times per day for Partial No
12 weeks
F 46 No Tetracycline rinses (0.25%, 5 mL for 1 min) 2 times per day for Complete No
12 weeks
M 24 No Tetracycline rinses (0.25%, 5 mL for 1 min) 2 times per day for Complete 5 months
12 weeks
M 1.5 Yes -
Lamey et al.6 Tetracycline 250 mg once per day for 4 weeks No
Penicillin 250 mg once per day for 2 weeks No
M 24 Yes Tetracycline 250 mg 4 times per day for 4 weeks Partial 8 weeks/Tetracycline
Tetracycline 250 mg once per day for 30 weeks Partial 250 mg/wk

CASE AND RESEARCH LETTERS

M 52 No Amoxicillin 250 mg 3 times per day for 4 weeks Partial 8 weeks/Amoxicillin
Minocycline 50 mg 2 times per day for 6 weeks No 250 mg/wk
F 11 No Penicillin 250 mg 4 times per day for 4 weeks Partial Yes/Penicillin
Penicillin 250 mg once per day for 20 weeks Partial 250 mg/wk
M 32 Yes Tetracycline 250 mg 4 times per day for 4 weeks Partial 10 weeks/No
Amoxicillin 250 mg 3 times per day for 4 weeks Partial
464

F 6 Yes Amoxicillin 125 mg 3 times per day for 4 weeks No -

Otobe et al.4 M 10 No Tetracycline rinses (0.25%) 2 times per day for 12 weeks Complete 4 months
F No -
Lim et al.7 36 Penicillin G procaine 1.2 MU IM once per day for 3 days No
Tetracycline rinse (0.25%), single dose Partial
Contreras-Steyls et al.5 M 26 Yes Doxycycline 200 mg once per day and tetracycline rinses (0.25%) Complete -
2 times per day for 12 weeks
Satriano et al.8 M 15 Yes Chlorhexidine rinse (0.12%, 5 mL for 45 seconds) 2 times per day Partial Chlorhexidine rinses 1 wk
for 8 days per month
F 50 Yes Chlorhexidine rinse (0.12%, 5 mL for 45 seconds) 2 times per day Partial Chlorhexidine rinses 1 wk
for 8 days per month
Piqué et al.2 M 46 No Amoxicillin 500 mg 3 times per day for 10 days No -
Retinoic acid (0.01% aqueous solution) for 4 weeks Complete Intermittent regimen of
topical retinoids
Becker et al.9 F 12 No Tetracycline rinses (0.25%, 2 times per day) for 12 weeks Partial Tetracycline rinses ad
libitum
Amores-Martín et al.* M 46 No Oral adhesive excipient containing 0.1% triamcinolone No -
acetonide and 0.1% retinoic acid once per day for 8 weeks
Doxycycline 100 mg once per day for 6 weeks Partial No

Abbreviations: F, female; IM, intramuscular; MU, million units; M, male.

* Present case.
 ACTAS Dermo-Sifiliográficas 112 (2021) 463---483

one of the lesions on the buccal mucosa revealed epithelial Analysis of therapeutic response as a function of a family
hyperplasia, edema, and discrete cytoplasmic clearance in history of WSN suggests that the absence of a family his-
squamous cells. Taken together with the clinical context, tory does not greatly increase the likelihood of a response
these findings were compatible with WSN. to treatment, but is associated with a greater clinical
Treatment for 2 months with topical triamcinolone ace- response.
tonide (0.1%) and retinoic acid (0.1%) in oral adhesive The new WSN case presented here, in which the patient
excipient resulted in no clinical improvement, and it was showed a satisfactory clinical response to oral doxycycline
decided to begin treatment with oral doxycycline (100 mg/d) (100 mg/d for 6 weeks), provides additional data on the
for 6 weeks. The extension and texture of the lesions use of oral tetracyclines to treat this condition. We believe
improved by the end of the treatment cycle, providing an it is important to have a knowledge of the clinical evi-
acceptable aesthetic result, and the patient remained stable dence supporting the different treatments used to date to
for the next 6 months (Fig. 1C and D). ensure selection of the most appropriate therapies for these
WSN is a rare, autosomal dominant disease with incom- patients.
plete penetrance, despite isolated reports of cases with
no family history.1,2 It was first described by Hyde in Conflicts of Interest
1909.1 Clinically, it is characterized by bilateral, well-
defined, villous white plaques with a spongy texture,
usually located on the oral mucosa, often with involve- The authors declare that they have no conflicts of interest.
ment of the bite line and the anterior third of the buccal
mucosa.1,3 It usually manifests during childhood or ado- References
lescence, with no sexual predisposition, and the lesions
tend to remain stable throughout life. Histology shows
acanthosis with intercellular edema and vacuolization, 1. Cai W, Jiang B, Yu F, Yang J, Chen Z, Liu J, et al.
as well as parakeratotic or orthokeratotic hyperkerato- Current approaches to the diagnosis and treatment
sis in the superficial layers.4,5 Diagnosis is based on of white sponge nevus. Expert Rev Mol Med. 2015;
clinical---pathological correlation and, where possible, anal- 17:e9.
2. Piqué Durán E, Palacios Llopis S, Jordán Sales D. Leucoedema
ysis of mutations in keratin 4 (KRT4) and keratin 13
frente a nevo blanco esponjoso. A propósito de un caso. Actas
(KRT13), genes responsible for epithelial keratinization.1 Dermosifiliogr. 2000;91:408---11.
The differential diagnosis should primarily include oral can- 3. Otobe IF, de Sousa SOM, Matthews RW, Migliari DA.
didiasis, frictional leukokeratosis, leukoedema, leukoplakia, White sponge naevus: improvement with tetracycline mouth
and lichen planus.1,2 rinse: report of four cases. Clin Exp Dermatol. 2007;32:
Although WSN is a benign and asymptomatic disease, its 749---51.
effects on mucosa texture and aesthetics are a source of dis- 4. Otobe IF, de Sousa SOM, Migliari DA, Matthews RW.
comfort for many patients. Multiple treatments have been Successful treatment with topical tetracycline of oral
tested for WSN (Table 1). Some have proven of little bene- white sponge nevus occurring in a patient with sys-
fit, producing variable results, and there is no well-defined temic lupus erythematosus. Int J Dermatol. 2006;45:
1130---1.
therapeutic protocol.
5. Contreras-Steyls M, López-Navarro N, Herrera-Acosta
Partial and complete responses have been described E, Herrera-Ceballos E. Nevus blanco esponjoso: buena
in patients treated with topical tetracyclines. The best respuesta al tratamiento con tetraciclinas. Piel. 2012;27:
results have been described in patients treated with 537---9.
0.025% tetracycline rinses 2 times per day for 12 6. Lamey PJ, Bolas A, Napier SS, Darwazeh AM, Macdonald DG.
weeks. However, good responses have been reported Oral white sponge naevus: response to antibiotic therapy. Clin
in 2 cases treated with oral tetracyclines, in line Exp Dermatol. 1998;23:59---63.
with our findings. The paucity of publications makes 7. Lim J, Ng SK. Oral tetracycline rinse improves symptoms of
it difficult to establish the best route of tetracy- white sponge nevus. J Am Acad Dermatol. 1992;26:1003---5.
cline administration. In WSN, the beneficial effect of 8. Satriano RA, Errichetti E, Baroni A. White sponge nevus treated
with chlorhexidine. J Dermatol. 2012;39:742---3.
second-generation tetracyclines such as doxycycline and
9. Becker LR, Lutz C, Erbard H, Bröcker EB, Hamm H. White sponge
minocycline can be attributed both to their anti- naevus successfully treated with tetracycline mouth rinse. Acta
inflammatory effects and their modulation of epithelial Derm Venereol. 1997;77:413.
keratinization.1 These properties constitute an advantage 10. Alvarez LG, Revuelta JAO. Efectos no antimicrobianos de las
over tetracycline.10 tetraciclinas. Rev Esp Quimioter. 2010;23:4---11.
Although WSN is not considered of microbiological ori-
gin, most of the treatments for which good outcomes have E. Amores-Martín,a,∗ G. Melé-Ninot,a
been reported to date are antimicrobial therapies, includ- E. Del Alcázar Viladomiu,a M.T. Fernández-Figuerasb
ing oral and topical antibiotics and antiseptics such as a
chlorhexidine.8 This suggests that certain microorganisms Servicio de Dermatología, Hospital Universitari Sagrat
may play a role in disease expression in genetically predis- Cor, Barcelona, Spain
b
posed individuals. However, further evidence is required to Servicio de Anatomía Patológica, Hospital Universitari
support this hypothesis. Sagrat Cor, Barcelona, Spain

465
 CASE AND RESEARCH LETTERS

∗
Corresponding author. https://doi.org/10.1016/j.adengl.2019.10.014
E-mail address: [email protected] 1578-2190/ © 2020 AEDV. Published by Elsevier España, S.L.U. This
(E. Amores-Martín). is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).

Buschke Sclerederma Treatment was started with ultraviolet A1 (UV-A1; UVA

302 L lamp, Waldmann® , Villingen-Schwenningen, Germany)
Refractory to Conventional at an initial dose of 5 J/cm2 , increasing in 10% increments
Treatment: Response to UV-A1 up to a maximum dose of 20 J/cm2 , administered in 3 ses-
Phototherapy夽 sions per week for a total of 28 sessions (cumulative dose,
291.09 J/cm2 ). This regimen had no adverse effects and
Escleredema de Buschke refractario a terapia resulted in improvements in dysphagia and mobility and a
convencional. Respuesta a UVA1 reduction in skin stiffness on the neck but not the buttocks.
Comparison of pre- and post-treatment elastography find-
To the Editor: ings showed a decrease in skin stiffness (Fig. 2C and D).
Scleredema in adults is a rare disease of the connec-
Scleredema belongs to the diffuse cutaneous mucinosis tive tissue, the clinical presentation of which depends on
group of disorders. It is also known as adult scleredema the disease with which it is associated.1 Scleredema associ-
or Buschke scleredema, after the dermatologist who first ated with diabetes mellitus is considered the most common
described it in 1902 in a patient with the classic manifesta- form, and affects obese adults with poorly controlled and
tions of the disease. It is considered a rare disease and its advanced diabetes. It begins insidiously, typically affect-
prevalence is unknown. No race-or sex-related differences ing the posterior area of the neck and thorax, sparing the
in prevalence have been reported, and it has been described extremities. Scleredema associated with a monoclonal gam-
in both pediatric and adult populations. mopathy is the least common form. The clinical presentation
A 62-year-old man with a personal history of long- is similar to that described in diabetes mellitus patients, but
standing hypertension, dyslipidemia, and type II diabetes the disease course is variable: spontaneous resolution has
mellitus with good metabolic control was initially evalu- been described in some cases, while in others the disease
ated in the digestive system unit for dysphagia for solids can be refractory to treatment and can become chronic.
that had begun several months earlier. Endoscopy had been In our patient, we identified 2 well-established clinical and
performed, but showed no evidence of disease. However, etiological factors.
a subsequent cervical thoracic abdominal pelvic computed Scleredema appears to be caused by irreversible colla-
tomography (CT) scan revealed edema of cervical, axil- gen glycosylation in the diabetes mellitus-associated form,
lary, and thoracic subcutaneous cellular tissue. The patient sensitization to collagen in the form associated with strep-
was admitted to the internal medicine unit. Examination tococcal infection, and chronic immune stimulation in the
revealed diffuse skin induration in the cervical region, shoul- form associated with monoclonal gammopathy.2
ders, back, and buttocks (Fig. 1B). Treatment poses a real challenge for the clini-
Blood tests showed an increase in free lambda chains cian. Treatment with immunosuppressants, intravenous
(570 mg/L) and immunofixation revealed a monoclonal immunoglobulins,3 and extracorporeal photopheresis4 has
component. The pathological examination revealed no epi- been described, with variable responses. However, pho-
dermal lesions and diffuse thickening in the middle and deep totherapy has always been considered a fundamental
dermis, with an increase in mucopolysaccharides between component of the treatment of adult scleredema. Due to
collagen bundles and an absence of inflammatory infiltrate its lower cost, greater accessibility, and, according to some
(Fig. 2B). authors, faster treatment response compared with other
Once the suspected diagnosis of adult scleredema was types of phototherapy,5 narrowband ultraviolet B (UV-B) has
confirmed, different treatments were performed succes- been the most commonly used modality.
sively, without response, and the patient’s clinical signs UV-A1 phototherapy (340---400 nm) appears to offer a bet-
progressively worsened, hindering the full range of move- ter response and lower rates of recurrence, as described
ments involving the shoulder and pelvic girdles. The
treatments administered included the following: pred-
nisone (tapering dose starting at 40 mg/d); methotrexate
(15 mg/wk for 4 months); methylprednisolone (6 pulses of
500 mg); intravenous immunoglobulin (3 g/wk for 3 cycles,
with little improvement); and cyclophosphamide.

夽 Please cite this article as: L. Linares-González, T. Ródenas-

Herranz, J.L. Espelt-Otero et al., Escleredema de Buschke Figure 1 A, Increased skin stiffness on the chest with papules
refractario a terapia convencional. Respuesta a UVA1, ACTAS Dermo- and peau d’orange in a V-shaped pattern. B, Waxy stiffness of
Sifiliográficas, 2021;112:466---468. the skin of the back.

466