Nevus Comedonicus Suppurativa: A Report of a Novel Entity

Abstract

Nevus comedonicus and hidradenitis suppurativa (HS) are disorders of the pilosebaceous unit sharing a similar pathogenesis of follicular occlusion. To our knowledge, less than 10 cases of HS-like lesions complicating nevus comedonicus have been reported. We describe a six-year-old female child with congenital linear nevus comedonicus in the left axilla and groin, complicated by recurrent HS-like lesions in the two years prior to presenting to our clinic. After a meticulous review of the literature, we propose a novel term, nevus comedonicus suppurativa, for this clinical entity.

Nevus comedonicus (NC) is a rare type of epidermal nevus that occurs either congenitally or in early childhood. It is clinically characterized by asymptomatic, closely arranged, dilated follicular openings with keratinous plugs. These resemble classical comedones and most commonly affect the head and neck region. Overstimulation of fibroblast growth factor receptor-2 (FGFR2) signaling with increased expression of interleukin-1α might be involved in its pathogenesis. Association of NC with a variety of skeletal, ocular, and central nervous system abnormalities is known as nevus comedonicus syndrome (NCS).1

NC is classified into two types: the classical type an inflammatory NC type characterized by papules and pustules.1 Here, we report a case of a prepubertal female patient presenting with hidradenitis suppurativa (HS)-like lesions complicating unilateral NC. We suggest using the term nevus comedonicus suppurativa to classify this type of NC.

CASE REPORT

A six-year-old female child, born out of nonconsanguineous marriage, presented with recurrent episodes of painful boils in the left groin and inner thigh for two years prior to visiting our clinic. The lesions subsided temporarily upon taking oral antibiotics and painkiller medications. The patient had not applied any topical medication or spray to the lesions. She did not have a history of systemic comorbidities and was not on chronic medications. Her past and family history was unremarkable.

The patient was febrile (100°F) but the rest of the systemic examination revealed no abnormalities. Lymphadenopathy was absent. During cutaneous examination, the left inguinal region showed closely arranged, comedone-like lesions in a linear fashion, extending from the left lower abdomen up to the inner thigh. The lesions were present against a background of a well-demarcated hyperpigmented patch. The comedones were accompanied by deep-seated nodules, abscesses, a few sinus tracts, and scarring (Figure 1). Linearly arranged grouped comedones with a background of hyperpigmentation were also observed in the left axilla (Figure 2). No evidence of inflammation was present in the axilla. Double comedones were not seen. The contralateral axilla and groin appeared normal. Further investigation revealed that comedone-like lesions had been present since birth but remained asymptomatic until two years before visiting our clinic. The patient had no history of premature menarche and a thorough physical examination did not reveal signs of endocrinal abnormalities, such as hirsutism, acne/oily skin, alopecia, acanthosis nigricans, clitoromegaly, or cushingoid appearance. Skeletal, ocular, and neurologic examination findings were within normal limits. The outcomes of routine blood investigations were also normal. Metabolic syndrome was ruled out on the basis of normal blood pressure, an absence of central obesity, and normal fasting blood sugar and lipid profiles. An ultrasound of the abdomen showed no feature of polycystic ovaries nor any other abnormality. Free T3, T4, and thyroid-stimulating hormone results were found to be within normal limits. Unfortunately, other hormonal investigations, such as testosterone levels, dehydroepiandrosteronsulfate, sex hormone-binding globulin, estrogen, follicle-stimulating hormone, luteinising hormone, prolactin, and fasting insulin levels were not completed due to a lack of testing materials in our institute and the inability of the patient’s family to pay for private testing.

FIGURE 1.

Linearly arranged, comedone-like lesions in the left inguinal region against a hyperpigmented patch, with deep-seated nodules, abscesses, sinus tracts, and scarring

FIGURE 2.

Linearly arranged, comedone-like lesions in the left axilla against a hyperpigmented patch

Culture from aspirated material was sterile. Two skin biopsies were sent, one from the axilla and one from the inguinal region, with differential diagnoses of NC and HS. A biopsy report from the axilla showed findings of hyperkeratotic epidermis with mild spongiosis, lymphocytic exocytosis, and a dilated hair follicle, consistent with the diagnosis of NC (Figure 3). The second biopsy showed hyperkeratotic and acanthotic epidermis along with areas of necrosis, dense granulation tissue, and suppurative inflammation, supporting the diagnosis of HS (Figure 4). Therefore, we made the diagnosis of unilateral linear NC without associated NCS yet complicated by HS-like lesions. The patient was prescribed an oral nonsteroidal anti-inflammatory drug and topical clindamycin. No improvements were observed after one week of this regimen, so she was advised to take oral amoxicillin and clavulanic acid for five days and was planned to receive oral isotretinoin, but was lost to follow up.

FIGURE 3.

Histopathological photomicrograph (hematoxylin and eosin-stained section, original magnification ×100) showing hyperkeratotic epidermis with mild spongiosis, lymphocytic exocytosis, and a dilated hair follicle

FIGURE 4.

Histopathological photomicrograph (hematoxylin and eosin-stained section, original magnification ×40) showing hyperkeratotic and acanthotic epidermis with areas of necrosis, dense granulation tissue, and suppurative inflammation (hidradenitis suppurativa-like lesion)

DISCUSSION

HS is a chronic disabling disorder characterized by deep, tender subcutaneous nodules, sinuses, and fibrosis. It usually begins after puberty and the most commonly affected sites are the axillae, perianal region, and perineum. It was first thought to be a disease of the apocrine gland but, histopathologically, it has been shown to involve the pilosebaceous unit, whereas the apocrine gland can be secondarily infected. The alteration of the terminal follicular epithelium with dilatation and distortion of infundibulum leads to the occlusion of the affected hair follicle, eventually resulting in bacterial infection and inflammation.2

The noteworthy features of our case were the sites of involvement, distinctive morphology, and complication by HS-like lesions. In our patient, the unilateral axilla and groin were affected, but these sites are usually not affected by NC. Further, the lesions followed a linear pattern and were present against a background of a well-defined hyperpigmented patch. Hyperpigmentation was absent in the contralateral axilla and groin. To our knowledge, NC on the background of a hyperpigmented patch has not been described in the literature. A review of the patient’s history did not reveal the cause of hyperpigmentation, as the parents did not report the use of any spray or topical medication, indigenous or otherwise. Despite this, we still suspect some topical spray or medication as the cause of hyperpigmentation, due to its well-defined but bizarre margins, as if a liquid or a spray had trickled down the skin.

Descriptions of the inflammatory aspects of NC date back to 1933. Vasiloudes et al3 discussed five pediatric cases with inflammatory acneiform or cystic lesions on NC. Less than 10 cases of HS-like lesions in association with NC have been described in the worldwide literature (Table 1), to the best of our knowledge.4–10 In our patient, NC in the left axilla was noninflammatory (i.e., classical), whereas, NC in the left inguinal region had evolved into hidradenitis-like lesions in the two years prior to the patient presenting to our clinic. The role of mechanical stress by tight clothing on the diseased follicles of NC has been hypothesized to cause HS-like lesions.3 Histopathologically, HS-like lesions are indistinguishable from the classical HS. The only differentiating point between the two is that HS is a primary disease of the pilosebaceous unit usually occurring after puberty, whereas HS-like lesions arise secondarily on the already diseased follicles of NC due to mechanical stress, generally affecting prepubertal children .2,4,5,7–10 NC has a benign clinical course not requiring any treatment, unless it evolves into HS-like lesions. The treatment of such complicated lesions is, in general, unsatisfactory, due to the difficulty in approaching such lesions. Some potential therapeutic options are oral and topical antibiotics, oral isotretinoin, CO₂ and erbium-doped yttrium aluminium garnet lasers, surgical excision, needle aspiration or drainage, and cryotherapy.2,11 Recently, Sahu et al10 discussed the role of the biologic adalimumab for treating HS-like lesions in a prepubertal female patient with NCS. Although isotretinoin has not been recommended in the treatment guidelines for HS, various studies have investigated it as a possible therapeutic option.11 While the response in severe disease is unsatisfactory, some reports suggest a favorable response with isotretinoin treatment in younger female patients without obesity with mild to moderate HS and a history of or coexisting acne.11 Moreover, pretreatment with isotretinoin at 0.5 to 1mg/kg daily for a few months before surgery has been shown to reduce the inflammatory components.11 Adverse effects of isotretinoin, particularly teratogenicity and concerns regarding depression and suicide ideation, limit the degree of comfort with which isotretinoin is prescribed in the pediatric population, adolescents, and patients who can become pregnant.12 Frequent side effects of isotretinoin include cheilitis and xerosis, which usually respond well to the liberal use of emollients. An isotretinoin symptom survey was designed to assess the presence or absence of 13 possible adverse effects: dry lips, dry/bloodshot eyes, dry skin, muscle aches/pain, nosebleed, frequent headache, mood swings, depression, suicidal thoughts, paronychia, rash, trouble with night vision, and severe sun sensitivity/sunburn. While the monitoring of liver function tests and lipid profile remain essential, simple tools like the described isotretinoin symptom survey might be useful for monitoring any adverse effects.11,12

TABLE 1.

Summary of the literature review

PATIENT’S AGE AND SEX	CUTANEOUS FINDINGS	SYSTEMIC ASSOCIATIONS	DIAGNOSIS	TREATMENT GIVEN	RECURRENCE
Dufour et al4
4 months, female	A congenital lesion in the left groin, with follicular dark spots; upon follow up at 14 months, purulent secretion with hypertrophic nodules in the medial part of the nevus	None	Nevus comedonicus complicated by HS-like lesion (biopsy-proven)	Antibiotic therapy administered but not successful	NA
Qian G et al5
19 years, female	Segmentally arranged comedones on trunk, face, and limbs; hairless patch on scalp with comedones, atrophic pits; nodules, ulcers, intercommunicating sinus tracts, scars over left axilla	Nystagmus, decreased vision, lenticular opacities, scoliosis with spina bifida	NCS complicated by HS-like lesions (biopsy-proven)	Oral acitretin 0.5mg/kg daily combined with antibiotic ointment	Yes; mean frequency of inflammatory episodes reduced from 6–7 to 1–2 times per year
Higgins et al7
49 years, male	A 29-year history of multiple abscesses in buttock, inguinal, and axillary regions; back was studded with innumerable large comedones and significant scarring	Yes (details not provided)	NCS complicated by HS-like lesions, positive FGFR2 mutation	Resistant to topical and systemic antibiotics, dapsone, retinoids, zinc supplements, PUVA, infliximab; surgical interventions included excision of the left axilla and shoulder region and a transposition flap	Yes
Ravaioli et al8
9 years, female	5-cm diameter lesion on right axilla with grouped follicular openings and black keratin plugs, inflamed nodule lasting 4 weeks	None	NC complicated by HS-like cyst (biopsy-proven)	Short-course antibiotic therapy, excision of entire affected area in 2 stages occurring 6 months apart	Recurrence after oral medication; no recurrence after excision at 2-year follow-up visit
Manikavachakan et al9
25 years, male	Grouped comedone like lesions extending from left anterior chest to left back, including inflammatory lesions and scarring in left axilla	None	NC with HS-like lesions (histopathologically proven)	Wide local excision of left axillary skin and subcutaneous fat, followed by resurfacing and transposition of flap	No
Sahu et al10
6 years, female	Generalized comedones over neck, chest, axillae, groins, genitalia, buttocks, and thighs with widespread suppuration and scarring	Moderate cognitive disability, oligodontia, bilateral cataract, decreased vision, supernumerary toes	Bilateral NCS with HS-like lesions (biopsy-proven)	Oral clindamycin and rifampicin for 2 months, followed by retinoids, two injections of adalimumab 40mg completed 4 weeks apart, second course repeated after 3 months	Multiple previous episodes of recurrence, but sustained improvement after adalimumab

HS: hidradenitis suppurativa; FGFR2: fibroblast growth factor receptor-2; NC: nevus comedonicus; NCS: nevus comedonicus syndrome; NA: not applicable

Besides nevus comedonicus, few case studies have shown an association of HS-like lesions in the setting of other dermatological disorders sharing pathogenesis of follicular occlusion, such as steatocystoma multiplex, pityriasis rubra pilaris, and acanthosis nigricans.1,13–17 The evolution of steatocystoma multiplex into a suppurative form as a result of the development of HS-like lesions is referred to as steatocystoma multiplex suppurativum.13–17 This term was probably introduced due to a distinct clinical behavior and challenging management of the latter compared to the classical steatocystoma multiplex.

Similar to steatocystoma multiplex suppurativum, this new variant, in which HS-like lesions complicate NC, also deserves special recognition in the literature owing to its distinction from classical NC in its clinical presentation, recurrent course, recalcitrant nature to treatment, and decreased patient quality of life. Hence, the label nevus comedonicus suppurativa is suggested for this novel entity.