Bernard Cohen, MD

The parents of a healthy 20-month-old boy ask for advice about a birthmark on his lower back (Figure 1). The lesion is asymptomatic and has grown proportionately with their son.

Diagnosis: Congenital smooth muscle hamartoma

The child is noted to have a soft, partially compressible, nontender, skin-colored smooth plaque measuring approximately 5.5 cm by 3 cm with overlying hypertrichosis extending from the midline lower lumbar back to the middle-right lower lumbar back. Upon stroking the lesion, it becomes more raised and indurated transiently (Figure 2). There are no other similar growths anywhere else on the body. An ultrasound performed at an outside hospital revealed no underlying spinal abnormalities.

Smooth muscle hamartoma (SMH) is an innocent cutaneous lesion that can be categorized into congenital or acquired types.

 The congenital form of SMH is generally sporadic, although a familial case has been described.

 Smooth muscle hamartoma is occasionally referred to as “arrector pili hamartoma” because the malformation arises from disorganized proliferation of the smooth muscle cells in the arrector pili muscle.

 The etiology of SMH is unclear, but it likely arises secondary to a developmental anomaly of that tissue.

The involvement of the arrector pili muscle is responsible for the characteristic “pseudo-Darier sign” in which the lesion becomes indurated or elevated upon stimulation of that muscle layer through stroking of the lesion.

 The patient may report a similar presentation when exposed to cold.

 The presence of this sign is suggestive of retained functional activity of the smooth muscle fibers and can distinguish SMH from similarly appearing lesions such as a congenital melanocytic nevus, potentially obviating the need for removal of this benign malformation.

 On histology, SMH appears as disseminated proliferation of smooth muscle cells in large, randomly oriented bundles usually located in the reticular dermis.

The prevalence of SMH has been estimated at between 1 in 1000 and 1 in 2700 live births, with a reported male predominance in its development.

 It often presents with hypertrichosis and/or hyperpigmentation, although these features tend to diminish with age.

Smooth muscle hamartoma usually presents as a solitary lesion, although it has occasionally been reported in a diffuse pattern associated with other complications as part of the Michelin tire baby syndrome (MTBS).

Smooth muscle hamartoma can be confused with congenital melanocytic nevus, which also can present as a raised lesion with hyperpigmentation and hypertrichosis, especially when the pseudo-Darier sign is absent.

 On dermoscopy, the patterns found in pigmented nevi are not present. Biopsy of the lesion should be performed prior to excision because selective congenital melanocytic nevi may need to be removed for their malignant potential whereas SMH is fully benign,

 and SMH is easily distinguishable from congenital melanocytic nevus on histopathology.

Smooth muscle hamartoma also can masquerade as Becker melanosis and have a similar clinical and histologic appearance to those lesions.

 Although hypertrichosis, hyperpigmentation, and smooth muscle proliferation are seen in both lesions, smooth muscle proliferation is dominant in SMH whereas Becker melanosis has more robust hypertrichosis and hyperpigmentation, which both tend to worsen with age unlike in SMH.

 The 2 lesions can be differentiated by long-term follow-up to see whether worsening or improvement in the hypertrichosis and hyperpigmentation occurs.

Patients with clinically ambiguous lesions should have an evaluation by a dermatologist, and some lesions may require a biopsy to make a specific diagnosis.

 Parents should be reassured that the SMH lesion is benign and does not require treatment. They also should be advised that any hypertrichosis or hyperpigmentation will improve over time.

 If cosmetic therapy is desired by the parents or patient, treatment can include laser therapy to reduce the burden of hypertrichosis and hyperpigmentation or surgical excision.

The patient’s parents were reassured that the finding was a common benign lesion and had no malignant potential. They were advised that the lesion would likely continue to grow proportionately with the child, that it could be removed if it became bothersome, and that routine monitoring would be sufficient for now.

1. Slifman NR. Harrist TJ, Rhodes AR. Congenital arrector pili hamartoma. A case report and review of the spectrum of Becker's melanosis and pilar smooth-muscle hamartoma. 

2. Gualandri L, Cambiaghi S, Ermacora E, Tadini G, Gianotti R, Caputo R. Multiple familial smooth muscle hamartomas. 

3. Schmidt CS, Bentz ML. Congenital smooth muscle hamartoma: the importance of differentiation from melanocytic nevi. 

4. BilgiÃ§ Ã, TunÃ§ez AkyÃ¼rek F, Altinyazar HC. Pseudo Darier sign: a distinctive finding for congenital smooth muscle hamartoma. 

5. Raboudi A, Litaiem N. Congenital smooth muscle hamartoma. 

[Internet]. Updated August 11, 2019. Accessed May 1, 2020. 

https://www.ncbi.nlm.nih.gov/books/NBK545188/

6. Goldman MP, Kaplan RP, Heng MC. Congenital smooth-muscle hamartoma. 

Articles

The parents of a healthy 20-month-old boy ask for advice about a birthmark on his lower back. The lesion is asymptomatic and has grown proportionately with their son. What's the diagnosis?

Persistent birthmark grows on a toddler’s back

An otherwise healthy 5-month-old girl presents with an asymptomatic, rapidly growing, firm, smooth nodule on the side of her left fifth finger since she was 2 months of age (Figure).

Diagnosis: Infantile digital fibroma (IDF)

Infantile digital fibromas (IDFs), also known as inclusion body fibromatosis or recurring digital fibrous tumors of childhood, are rare, benign, fibromatous tumors most commonly located on the dorsolateral aspects of the fingers and toes.

 These fibromas typically develop during the first year of life; however, they are present at birth in up to one-third of cases.

 In rare circumstances, they can appear during adulthood.

Infantile digital fibromas initially exhibit a period of slow growth, which is followed by a rapid growth phase over 10 to 14 months.

 They can ultimately reach sizes ranging from 3 mm to 35 mm.

 They subsequently regress without treatment within 2 to 3 years.

These fibromas classically appear as single to multiple, smooth, firm, skin-colored to pink nodules on the dorsolateral aspects of the fingers and toes.

 Interestingly, the thumbs and great toes are typically spared.

Histopathologic examination reveals proliferations of spindle-shaped myofibroblasts admixed with collagen bundles within the dermis.

 The presence of eosinophilic inclusions arranged in a perinuclear fashion within the myofibroblast cytoplasm is pathognomonic for IDF. Masson’s trichrome stains these inclusions red, whereas phosphotungstic acidhematoxylin (PTAH) stains them purple.

The differential diagnosis for IDF includes periungual fibromas, supernumerary digits, and acral fibrokeratomas.

Periungual fibromas are pink to skin-colored papules that develop from the proximal nail fold.

 They are associated with tuberous sclerosis and von Recklinghausen disease.

 In fact, approximately 50% of patients with tuberous sclerosis have multiple periungual fibromas, also known as Koenen tumors.

 However, solitary periungual fibromas can also be seen in the general population.

 They can produce pressure on the nail matrix, resulting in a longitudinal groove in the nail plate.

Supernumerary digits are soft tissue growths that lack a skeletal component.

 They can appear as fleshy or verrucous-like papules, or present as larger, pedunculated nodules. Supernumerary digits are present at birth and often found bilaterally, with the most common location being the lateral aspect of the fifth finger.

Acral fibrokeratomas, also known as acquired digital fibrokeratomas, are relatively rare, benign skin growths.

 They present as skin-colored to pink, faintly keratotic papulonodules. Acral fibrokeratomas are typically solitary and tend to occur on the fingers and toes of middle-aged adults. They also can be seen on the palms and soles.

Currently, there is no agreed-upon treatment approach for IDFs. Surgical excision is a viable option; however, recurrence is common with an estimated recurrence rate between 61% to 74%.

 Therefore, surgical excision is typically reserved for symptomatic cases causing pain or functional impairment.

Nonsurgical options include topical steroids, intralesional triamcinolone, or intralesional 5-fluorouracil (5-FU).

 However, these nonsurgical approaches have not been studied extensively, given the rarity of this condition. Eypper and colleagues recently proposed a management algorithm for IDFs: If symptomatic, proceed to surgical excision; if asymptomatic but greater than 1 cm, treat with intralesional triamcinolone or intralesional 5-FU; if asymptomatic and less than 1 cm, continue to monitor.

A shave biopsy confirmed the diagnosis of IDF in this infant girl. The growth continued to rapidly enlarge, causing slight distortion of the distal interphalangeal joint. Surgical excision was performed at the age of 14 months without complication. However, at age 3 years the patient returned to the clinic for evaluation of a new growth on the dorsolateral aspect of her distal left fourth finger, clinically consistent with IDF. There also was evidence of recurrence of the previously excised IDF on her left fifth finger.

Given the small size of these growths (both less than 1 cm), clinicians opted to closely monitor the patient and prescribed clobetasol 0.05% cream to be used 2 times daily on the affected areas.

1. Bolognia JL, Jorizzo JL, Schaffer JV, et al. 

. London: Elsevier Ltd; 2012:1009, 1144, 1964-1965, 1969-1970.

2. Heymann WR. Infantile digital fibromatosis. 

3. Eypper EH, Lee JC, Tarasen AJ, Weinberg MH, Adetayo OA. An algorithmic approach to the management of infantile digital fibromatosis: review of literature and a case report. 

4. PlusjÃ© LG, Bastiaens M, Chang A, Hogendoorn PC. Infantile-type digital fibromatosis tumour in an adult. 

5. Laskin WB, Miettinen M, Fetsch JF. Infantile digital fibroma/fibromatosis: a clinicopathologic and immunohistochemical study of 69 tumors from 57 patients with long-term follow-up. 

6. Niamba P, LÃ©autÃ©-LabrÃ¨ze C, Boralevi F, et al. Further documentation of spontaneous regression of infantile digital fibromatosis. 

7. Marks E, Ewart M. Infantile digital fibroma: a rare fibromatosis. 

8. Ward PE, McCarthy DJ. Periungual fibroma. 

9. Boffeli TJ, Abben KW. Acral fibrokeratoma of the foot treated with excision and trap door flap closure: a case report. 

An otherwise healthy 5-month-old girl presents with an asymptomatic, rapidly growing, firm, smooth nodule on the side of her left fifth finger since she was 2 months of age.

Rapidly growing nodule on an infant’s finger

A healthy 3-year-old girl presents for evaluation of light brown spots on her trunk and extremities that have appeared over the last 2 years. The spots are not symptomatic but the girl’s parents are worried that she could have neurofibromatosis.

First described in 1869 by Nettleship and Tay, mastocytosis is a pathogenic expansion of mast cells.

 It is considered a clonal disease attributed to activation mutations found in the C-Kit gene, which leads to increased survival and proliferation of mast cells.

 Disease can be limited to the skin, or it can involve other organs such as the bone marrow, gastrointestinal tract, liver, or spleen.

 In children, 9 of 10 cases are cutaneous, the majority of which are urticaria pigmentosa (UP), also called maculopapular mastocytosis.

In a systematic review of 1747 cases by MÃ©ni and colleagues, 90% of cases presented by the age of 2 years, and almost 70% of cases at least partially regressed.

 Urticaria pigmentosa is more common in boys, although the sex-ratio data inverts in adulthood.

In the Figure, note the lesion on the top-right side of the patient’s back. It urticated when rubbed while the area to the left with normal skin did not.

The characteristic lesions in UP are scattered small (1-cm to 2-cm), red-brown or yellow-tan thin papules or plaques that develop a wheal and erythema upon physical manipulation (Darier sign). These lesions also can have increased skin markings. Most patients will lack systemic symptoms such as flushing, gastrointestinal (GI) symptoms, bone pain, syncope, or bronchospasm. If the exam is equivocal, biopsy can be done and will show increased mast cell numbers or activating KIT mutations.

It is essential to distinguish these lesions from cafe-au-lait macules (CALM), which can be associated with a diagnosis of neurofibromatosis type 1 (NF1). The borders of UP lesions are ill defined compared with the well-demarcated borders of CALM. Also, CALM will not urticate. Severe cases of UP can blister and can be mistaken for bullous dermatoses such as epidermolysis bullosa and linear immunoglobulin (Ig) A bullous dermatosis. Lastly, these lesions can be confused with arthropod bites or juvenile xanthogranulomas.

Because these lesions will likely resolve without sequelae, patients can be monitored annually at their well-child visits, and no treatment is required. Symptomatic therapy with topical corticosteroids and oral antihistamines can be offered to combat pruritus.

 Although systemic involvement is rare in children, it can be evaluated and ruled out with a complete blood count with differential, liver function tests, and a serum total tryptase.

 Patients with systemic symptoms can be managed with oral antihistamines, antileukotriene drugs, and omalizumab.

Clinicians reassured the patient and her mother that the spots were benign mastocytomas rather than cafÃ©-au-lait macules and that they did not have to worry about neurofibromatosis. The mother was counseled about the benign nature of the spots and told that there was no treatment or further evaluation needed for her daughter unless anything changed.

1. Matito A, AzaÃ±a JM, Torrelo A, Alvarez-Twose I. Cutaneous mastocytosis in adults and children: new classification and prognostic factors. 

3. Vardiman JW. The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues: an overview with emphasis on the myeloid neoplasms. 

4. Bolognia J, Schaffer JV, Duncan KO, Ko CJ. 

5. Heide R, Beishuizen A, De Groot H, et al; Dutch National Mastocytosis Work Group. Mastocytosis in children: a protocol for management. 

6. Carter MC, Clayton ST, Komarow HD, et al. Assessment of clinical findings, tryptase levels, and bone marrow histopathology in the management of pediatric mastocytosis. 

7. Castells M, Metcalfe DD, Escribano L. Diagnosis and treatment of cutaneous mastocytosis in children: practical recommendations. 

Fuzzy brown spots on a healthy 3-year-old

A 16-year-old girl presents to the clinic for acne follow-up and mentions that her palms wrinkle significantly after only a few minutes of immersion in water. She is otherwise well and has no significant past medical history.

After brief (minutes of) exposure to water, the patient experiences exaggerated wrinkling of the palms along with white, edematous papules that may coalesce into plaques. Upon removal from water, her skin changes typically resolve in less than 1 hour with drying of the skin. Although the diagnosis is made clinically, histology of the skin reveals dilated eccrine ducts.

Aquagenic wrinkling of the palms (AWP) has a strong association with cystic fibrosis (CF), affecting up to 84% of patients with CF and up to 25% of carriers.

 In patients with CF, aquagenic wrinkling typically develops faster (within 2 to 3 minutes of immersion in water) than in carriers (5 to 7 minutes).

The mechanism responsible for this phenomenon is not fully understood. However, it is thought that the increased tonicity of sweat in patients with CF induces an osmotic shift of water across the epidermis.

 Because mutations in the gene encoding the CF transmembrane conductance regulator (

 gene) protein are responsible for the pathologic dysregulation of epithelial fluid transport in CF, 

-directed therapies have been successful in improving pulmonary function and other clinical outcomes for some patients.

 Interestingly, pharmacologic therapy for CF that potentiates 

 function also has been shown to reduce aquagenic wrinkling.

Whereas AWP is most prominently described in association with CF, there have been reports of AWP in healthy individuals as well as in patients with marasmus and atopic dermatitis.

 Certain drugs (eg, selective cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDS), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) also may be associated with cases of aquagenic wrinkling by causing dysregulation of aquaporins and abnormal water transport across cell membranes in the skin.

Hyperhidrosis is a condition of unknown etiology characterized by excessive sweating that is generally localized to local body region (ie, palms). It can affect patients of any age but is most commonly seen in adolescents and young adults. Although palmar hyperhidrosis has been associated with the development of AWP,

 the former is a distinct disorder with much higher prevalence and is not known to have association with CF.

Hereditary papulotranslucent acrokeratoderma (HPA) is a congenital disorder characterized by yellow-white papules and plaques at the borders of the palms and soles.

 However, normal eccrine glands are seen on biopsy. In contrast, skin changes in AWP occur transiently in response to water exposure and involve dilated eccrine glands on histology.

Aquagenic wrinkling of the palms itself is benign and can be prevented by water avoidance. Severe cases can be treated with a topical antiperspirant (eg, aluminum chloride).

In this patient, AWP was an isolated finding without accompanying symptoms or family history suggestive of CF. However, reports have shown that AWP can be the first presenting sign of CF carrier status in otherwise healthy individuals, or of nonclassical CF that involves fewer organ systems and that is often diagnosed later in life.

 Given this finding, the patient was referred for sweat chloride testing.

With the patient’s sweat chloride level of 26 mmol/L (reference range: 0-29), she was categorized as “cystic fibrosis unlikely.” Although there have been cases of CF patients and carriers with normal sweat chloride tests, a previous study did not recommend genetic testing for patients with isolated aquagenic wrinkling without symptoms related to, or family history of, CF.

 This was consistent with recommendations from the pediatric Pulmonary Service.

Given the high prevalence of AWP in patients with CF and its association with gene mutation carriers, AWP should prompt preliminary workup for CF.

A careful history should be elicited for family history of CF and associated symptoms (eg, chronic fatigue, diabetes mellitus, nutritional deficiencies, recurrent pancreatitis, diarrhea, acholic stools, bowel obstructions, nasal polyps, chronic sinusitis, chronic coughing, wheezing).

 Digital clubbing on exam may also suggest pulmonary disease.

The index of suspicion based on history and exam may then guide management toward the sweat chloride test or more definitive genetic testing.

1. Thomas JM, Durack A, Sterling A, Todd PM, Tomson N. Aquagenic wrinkling of the palms: a diagnostic clue to cystic fibrosis carrier status and non-classic disease. 

2. Arkin LM, Flory JH, Shin DB, et al. High prevalence of aquagenic wrinkling of the palms in patients with cystic fibrosis and association with measurable increases in transepidermal water loss. 

3. Grasemann H, Ratjen F, Solomon M. Aquagenic wrinkling of the palms in a patient with cystic fibrosis. 

4. Chinazzo C, De Alessandri A, Menoni S, Romanisio G, Rebora A, Rongioletti F. Aquagenic wrinkling of the palms and cystic fibrosis: an Italian study with controls and genotype-phenotype correlations. 

5. Gild R, Clay CD, Morey S. Aquagenic wrinkling of the palms in cystic fibrosis and the cystic fibrosis carrier state: a case-control study. 

6. Park L, Khani C, Tamburro J. Aquagenic wrinkling of the palms and the potential role for genetic testing. 

Bernard Cohen, MD

Articles

Persistent birthmark grows on a toddler’s back

Rapidly growing nodule on an infant’s finger

Fuzzy brown spots on a healthy 3-year-old

Girl’s hands shrivel when exposed to water