A Challenging Case of Cystic Acne

Abstract:  28 yo woman with 3.5 month history of cystic acne

HPI:  The patient's mother contacted us regarding her daughter, a 28 yo woman with severe cystic acne for over three months.  She has had acne in the past, but has also enjoyed long acne free periods as well. No recent changes in medications. The patient has a complicated medical and psychiatric history.  She has had a diagnosis of bipolar illness disease (BPD) for greater than ten years.  She has two children but her pregnancies were possibly complicated with hypercoagulation secondary to Protein S (history vague).  She has been hospitalized for psychiatric disease.  Presently, shes care for her children and is in school hoping to get a degree in social work.  She is on a host of medications which include lithium, a mini OCP (progesterone only because estrogen is contraindicated due to Protein S).  She is understandably depressed as a result of her acne.

O/E: The patient is a sad looking woman who sat in the waiting room with a baseball cap low on forehead and head bowed. She has cores of small to moderate cysts covering face.  Back and chest clear.  She is aesthenic.

Phtotos:

Labs:  None yet

Questions:
It seems that periodically something triggers her acne.  What are your thoughts?
Workup:  Which serum androgens should be ordered?  I am considering Total and Free Testosterone and DHEA-S. 
Management:  Since estrogenic OCPs are contraindicated and tetracyclines have interactions with lithium, what is best approach?
Lithium and progesterone both can cause acne flares.  Do they act synergistically?
I started her on amoxicillin 500 mg tid until I get some better ideas.
There is a worrisome article on the use of isotretinoin in patients with BPD. (Ref 1)  Do you believe this?

References:
1. Psychiatric reactions to isotretinoin in patients with bipolar disorder.

Schaffer LC, Schaffer CB, Hunter S, Miller A.

J Affect Disord. 2010 May;122(3):306-8. doi: 10.1016/j.jad.2009.09.005.

Sutter Community Hospitals, United States. schafferpsych@sbcglobal.net

Conclusions: These results indicate that BD patients treated with isotretinoin for acne are at risk for clinically significant exacerbation of mood symptoms, including suicidal ideation, even with concurrent use of psychiatric medicines for BD. The clinical implications of this study are especially relevant to the treatment of patients with BD because acne usually occurs during adolescence, which is often the age of onset of BD and because a common side effect of lithium (a standard treatment for BD) is acne.  URL

2. [Retinoids: drug interactions]. [Article in French]

Berbis P.  Ann Dermatol Venereol. 1991;118(4):271-2.

Abstract There is little available literature on possible drug interactions involving retinoids despite their widespread use. Unlike some other molecules, the retinoids regardless of their generation do not entail a high risk of interference with other medications. A current study found that concomitant administration of etretinate did not significantly modify the timing or value of the peak serum level of 8 methoxy sporalene. Isotretinoin seems to have an inhibiting effect on certain microsomal hepatic and cutaneous oxydases. An isolated observation has been reported of reduced serum concentration of the antiepileptic Carbamazepine in a patient treated with isotretinoin for severe acne. The report, through unconfirmed, should prompt intensified monitoring of patients receiving antiepileptics and retinoids. Among potential pharmacodynamic interactions, studies with the most evident practical importance have assessed possible interference of orally administered retinoids with the efficacy of oral contraceptives (OCs). 1 study of isotretinoin and OCs concluded on the basis of serum levels of progesterone on the 21st or 22nd cycle day that there was no interference. Another study using the same evaluation criteria concluded that there is no interaction between the aromatic retinoids etretinate or acitretin and OCs. The use of low-dose progestins is however not recommended. A recent study on healthy volunteers demonstrated the absence of influence of acitretin on the efficacy of the antivitamin K agent phenprocoumon. The combination of cyclines with isotretinoin can cause intracranial hypertension and is formally contraindicated. Intracranial hypertension has also been reported with aromatic retinoids, which are not recommended. The combination of lithium and retinoids should also be avoided. Because of the additive effect of undesirable side effects, the combination of retinoids and potentially hepatotoxic molecules especially methotrexate and of isotretinoin and potentially photosensitizing molecules should be avoided..  URL.

3. Is thrombophilia testing useful?

Middeldorp S.

Hematology Am Soc Hematol Educ Program. 2011;2011:150-5. doi: 10.1182/asheducation-2011.1.150\

Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.

Abstract: Thrombophilia is found in many patients presenting with venous thromboembolism (VTE). However, whether the results of such tests help in the clinical management of such patients has not been determined. Thrombophilia testing in asymptomatic relatives may be useful in families with antithrombin, protein C, or protein S deficiency or homozygosity for factor V Leiden, but is limited to women who intend to become pregnant or who would like to use oral contraceptives. Careful counseling with knowledge of absolute risks helps patients in making an informed decision in which their own preferences can be taken into account. Observational studies show that patients who have had VTE and have thrombophilia are at most at a slightly increased risk for recurrence. In an observational study, the risk of recurrent VTE in patients who had been tested for inherited thrombophilia was not lower than in patients who had not been tested. In the absence of trials comparing routine and prolonged anticoagulant treatment in patients testing positive for thrombophilia, testing for such defects to prolong anticoagulant therapy cannot be justified. Diagnosing antiphospholipid syndrome (APS) in women with recurrent miscarriage usually leads to treatment with aspirin and low-molecular-weight heparin (LMWH), although the evidence to support this treatment is limited. Because testing for thrombophilia serves a limited purpose, this test should not be performed on a routine basis.  Free Full Text.

Psoriasis vs. PRP: Your Thoughts

Presented by Dr. Henry Foong, Ipoh, Malaysia
Abstract: A 65 year old man presented with a history of erythroderma for 3 weeks.

History: A 65 year old man presented with pruritic scaly erythematous patches on the chest about 3 weeks ago.  Then he noticed the rashes spreading to the abdomen and back.  Now it has spread to the face and both upper and lower extremities. He had no fever or other constituional symptoms.  He denied taking any previous medication or health supplements.There was no past history of psoriasis or eczema.

Examination showed extensive multiple scaly erythematous patches on the abdominal wall, entire back and thighs.  His scalp was scaly too.  Over the lower back and abdominal wall, the erythema was confluent and generalised with multiple erythematous patches with islands of white in between. The lesions has an irregular margin. There is no follicular hyperkeratosis.  The nails were normal. Both palms and soles appeared normal and not hyperkeratotic.

Photos:

Pathology: 

The epithelium shows parakeratosis. The squamous epithelium does not show spongiosis or basal layer degeneration. The upper dermis shows mild perivascular and interstitial infiltrates of lymphocytes and eosinophils. The deep dermis is normal. Features do not suggest psoriasis. 

INTERPRETATION

Features are compatible with pityriasis rubra pilaris without follicular involvement.

Diagnosis: Erythroderma - Extensive psoriasis vs pityriasis rubra pilaris

Reason for posting: This is an interesting diagnostic problem as whether erythroderma is due to PRP or psoriasis.  Though there are features of psoriasiform changes over the extremioties and lower back, the presence of "islands of white" within patches of erythema is suggestive of PRP. As our experience with generalised PRP is limited, it is difficult to make a definitve diagnosis.  A biopsy was done to help to make a more definitive diagnosis.  In terms of treatment, however, oral retinoids such as acitretin would be useful in both conditions.

Editorial Board

Yoon Cohen, D.O.

Dermatology Resident

Mesa, Arizona

( yoon@yooncohen.com )

David Elpern M.D.

The Skin Clinic

Williamstown, MA, USA

( kauai@bcn.net )

Henry Foong FRCP (Edinburgh)

Foong Skin Specialist Clinic

Ipoh, Malaysia

( bbfoong@gmail.com )

Stephanie Hu, M.D.

Department of Dermatology

New York University

New York, New York

( stephwhu@gmail.com )

Barry Ladizinski, M.D.

School of Public Health

Johns Hopkins University

Baltimore, Maryland

( barryladizinski@gmail.com )

Lichen Nitidus

Presented by Yoon Cohen, D.O.

Abstract: 13 year-old boy with a few years history of lichen nitidus

HPI:  This is a 13 year-old Hispanic boy who presented for treatment of warts. During the exam, multiple small white shiny dots were noticed. The patient has been aware of these asymptomatic lesions for the past few years.  He had been given triamcinolone 0.1% ointment bid, but forgot to apply it because it did not bother him. 

O/E:  There  are multiple pinhead-sized 1 mm white shiny flat-topped papules in an oval shape on the right knee.  

Dermatoscopic Photo:

Multiple small white circles
The dermoscopic image taken with the Canfield Dermatoscope with iPhone attachment

Diagnosis:
Lichen nitidus

Discussion:
While there are many dermoscopic studies on the skin cancers, there is a growing interest of dermoscopic features on other skin diseases such as inflammatory diseases, connective tissue disorders, or even psychogenic related skin diseases. Lichen nitidus is easily recognized clinically with experienced eyes. With my own interest in dermoscopy, I report an interesting dermoscopic finding of lichen nitidus. There are 1-2 mm multiple small white circles which represent subepidermal infiltrate of lymphocytes, histiocytes, and multinucleated giant cells in the dermal papillae. 

Lichen nitidus was first described by Pinkus in 1907. Lichen nitidus, which means shiny papules, is a relatively uncommon, asymptomatic, chronic eruption, consisting of minute sharply demarcated skin-colored papules. It has a predilection for males (4:1) and the mean age of onset was 7 yrs for males and 13 yrs for females. Typically, patients present for assessment with an asymptomatic or mildly pruritic eruption. The eruption may be localized to one or more areas or generalized in distribution. The pathogenesis of lichen nitidus is unknown. It was originally believed to be a form of tuberculid and more recently considered to be a variant of lichen planus. Histologially, lichen nitidus is characterized by a circumscribed collection of inflammatory cells in the papillary dermis that abuts the overlying epidermis. The inflammatory infiltrate consists of lymphocytes, histiocytes, and multinucleated giant cells. DIF negative.  Most cases require no treatment due to the asymptomatic nature of the eruption and tendency for spontaneous resolution. For symptomatic cases, moderately potent or potent topical steroid therapy may help. There are a number of anecdotal reports of improvement or clearance with narrow band UVB phototherapy, extensive sunlight exposure, oral astemizole, oral cetirizine-levamisol combination, topical dinitrochlorobenzene, itraconazole and oral cyclosporin. Oral retinoids have been used successfully in the treatment of palmoplantar lichen nitidus.

Reference:

Schachner LA, Hansen RC. Pediatric Dermatology. 4th edition. 2011
L. Nitidus eMedicine (free open access)

Comment: By DJ Elpern.  This is the first report of the dermatoscopic appearance of L. nitidus.  Yoon Cohen deserves credit for this observation.

Mycosis Fungoides

Abstract: 65 year-old man with 14 year history of mycosis fungoides (MF).

HPI:  This 65 yo man has had a dermatitis around his hips since childhood.  In 1999, a biopsy was done that was reported as "very suggestive of MF."  He was treated with PUVA in 1999  and since then with topical corticosteroids (initially clobetasol and more recently fluocinonide). His disease is either quiescent or has not progressed since diagnosis.

O/E:  There are patches and plaques on the left and to a lesser extent right hips.  Some atrophy and "cigarette paper changes" are present on the left hip.  There is no to minimal involvement elsewhere.  He has no lymphadenopathy.

Clinical Photos:

Pathology:  Photomicrographs courtesy of Deon Wolpowitz, M.D., Boston University SkinPath

Focal parakeratosis, flattened epidermis, lymphocytic exocytosis and "haloed lymphocytes" lining up along the  dermal epidermal junction and forming small intraepidermal aggregates, and intermittent moderate band-like lymphohistiocytic infiltrate.  These changes are suggestive of CTCL, MF type.

Diagnosis:  CTCL, MF type. Patient has had a rash in the area since childhood.  Since the pathological diagnosis was first made in 1999 his disease has not progressed much and is still probably Stage IA.

Questions:  Do you think this is early M.F.?  Could the poikilodermatous change be due to proponged use of topical corticosteroids? Will treatment make a difference?  He has read about new treatments.  We discussed imiquimod. Does anyone have experience with that?  How would you approach this patient?

References:

1.  [This valuable reference was kindly suggested by Barry Ladizinski, M,D.]  Defining early mycosis fungoides.
Pimpinelli N, Wood GS; et. al. International Society for Cutaneous Lymphoma.
J Am Acad Dermatol. 2005 Dec;53(6):1053-63. Review.
Abstract: This editorial review summarizes the results of 5 meetings sponsored by the International Society for Cutaneous Lymphoma at which the clinicopathologic and ancillary features of early mycosis fungoides were critically examined. Based on this analysis, an algorithm was developed for the diagnosis of early mycosis fungoides involving a holistic integration of clinical, histopathologic, immunopathologic, and molecular biological characteristics. A novel aspect of this algorithm is that it relies on multiple types of criteria rather than just one, for example, histopathology. Before its finalization, the proposed diagnostic algorithm will require validation and possibly further refinement at multiple centers during the next several years. It is anticipated that a more standardized approach to the diagnosis of early mycosis fungoides will have a beneficial impact on the epidemiology, prognostication, treatment, and analysis of clinical trials pertaining to this most common type of cutaneous lymphoma. 

2.  Treatment of cutaneous T cell lymphoma: current status and future directions.  Apisarnthanarax N, Talpur R, Duvic M.  Am J Clin Dermatol. 2002;3(3):193-215. Abstract: The treatment of cutaneous T cell lymphoma (CTCL), which includes mycosis fungoides and Sezary syndrome, has been in a state of continual change over recent decades, as new therapies are constantly emerging in the search for more effective treatments for the disease...  Read full abstract to give an idea of how complicated this is.

3. Imiquimod in mycosis fungoides. Free Open Access

Martínez-González MC, et. al.  Eur J Dermatol. 2008;18(2):148-52.

Abstract:  Imiquimod is a topically active imidazoquinoline immunomodulator agent. It works as an indirect antiviral and antitumoral and stimulates the production of INF-alpha and various other cytokines. We assayed topical imiquimod in treating early stages of mycosis fungoides. We applied imiquimod 5% cream in four patients with multi-treatment resistant plaques of MF (stages IA and IIB). We applied it on one patient in association with systemic INFalpha-2a. We observed a complete clinical clearance of the lesions in all four patients. In three cases we achieved a complete histopathological clearance and in one case a partial histopathological clearance. The patient treated with imiquimod and systemic INFalpha-2a showed the most spectacular improvement with a rapid total response. We ascribe this improvement to a synergic effect of imiquimod and systemic INFalpha-2a treatment. Before the introduction of imiquimod, this patient had been treated for 2 years with systemic INFalpha-2a alone, without any evidence of clinical response. Imiquimod could be an effective therapy for early-stage disease of CTCL, used alone or in combination with systemic immunomodulatory therapy.

Pigmented Macules of the Lips

The patient is a 70 year-old architect who presented for another problem.  Incidental hyperpigmented macules were noted on the lower lip.  No family members are similarly affected nor does he have a family hisrory of colon cancer.  He has had unremarkable colonoscopies.  The pigmentation began ~ 20 years ago.

O/E:  Hyperpigmented macules of lower lip.

Clinical Photo:

Diagnosis: Probable Laugier Hunziker syndrome is favored.

References:

1. Laugier Hunziker syndrome. Jabbari A, et. al. Dermatol Online J. 2010;16(11):23.

Abstract: Laugier Hunziker syndrome is a rare disorder that is characterized by adult-onset hyperpigmented macules of the lips, oral cavity, and fingertips. Longitudinal melanonychia is present in the majority of cases. We present a 45-year-old woman with adult-onset hyperpigmented macules of the oral cavity as well as linear melanonychia that involved multiple fingernails. The history, clinical examination, and paucity of laboratory abnormalities or systemic findings support a diagnosis of Laugier Hunziker syndrome.  Free Full Text.

2. Peutz-Jager Syndrome eMedicine.
Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited disorder characterized by intestinal hamartomatous polyps in association with a distinct pattern of skin and mucosal macular melanin deposition. Patients with PJS have a 15-fold increased risk of developing intestinal cancer compared with that of the general population.

Acanthosis Nigricans in an 8 year old girl

Abstract:  Eight year-old girl with acanthosis nigricans

Presented by: 

Dr. Soheila Sotoudeh

Children’s Medical Center

Tehran, Iran

History:  This 8- year-old girl, born of nonrelative parents, presented
with a one year history of darkening and thickening of body folds especially neck and axilla.  It began with pruritic, hyperpigmented and corrugated
plaques on her neck, axilla, groin and perioral and periumbilical area.
Family history is negative for any skin disease. Drug history: levothyroxine
Her disease is gradually progressive.

O/E:  She is otherwise healthy. Her weight and height is in 50 percentile. There are hyperpigmented and corrugated plaques on her neck, axilla, groin and perioral and periumbilical area.

Photos:

Lab:  Routine hematologic and biochemical parameters (including
blood glucose and insulin level) were normal. Chest x-ray and abdominopelvic sonography were normal. Clinical screening for evidence of internal malignancy was negative.

Histopathology: Skin biopsy showed hyperkeratosis, papillomatosis and
acanthosis, mild pigment incontinence and a sparse perivascular
inflammatory dermal infiltrate.

Diagnosis: Acanthosis nigricans

Comments and Questions: My diagnosis was Acanthosis Nigricans. I have prescribed Acitretin 0.5 mg/kg for more than 3 months but without remarkable response.

1-Do you agree with the diagnosis of acanthosis nigricans?

2-What type of acanthosis nigricans does she have?

3-Do you recommend genetic testing?

4-What other treatment do you recommend?

References:

1. Remission of acanthosis nigricans, hypertrichosis, and Hashimoto's thyroiditis with thyroxine replacement.

Dix JH, Levy WJ, Fuenning C.  Pediatr Dermatol. 1986 Sep;3(4):323-6.

Abstract: Hypothyroidism is not commonly associated with acanthosis nigricans (AN). We examined a 13-year-old girl with AN, hypertrichosis, and Hashimoto's thyroiditis. Overt biochemical hypothyroidism, thyroid enlargement, and positive titers of antimicrosomal and antithyroglobulin antibodies confirmed Hashimoto's thyroiditis. Both AN and hypertrichosis resolved with thyroid hormone replacement. There was no evidence of insulin resistance, polycystic ovarian disease, lipoatrophy, or other endocrine dysfunction, or of malignancy. In two patients from the literature with AN and hypothyroidism, AN was attributed to associated thyroid carcinoma or insulin resistance, rather than coexisting hypothyroidism. Since the skin lesions improved with thyroid hormone therapy in those two patients and in ours, hypothyroidism appears to be directly involved in the pathogenesis of AN.

2. A Case of Generalized Acanthosis Nigricans with Positive Lupus Erythematosus-Related Autoantibodies and Antimicrosomal Antibody: Autoimmune Acanthosis Nigricans?  Y. Kondo,et. al. Case Rep Dermatol. 2012 Jan-Apr; 4(1): 85–91.  Free Full Text Open Access.

3. Acanthosis nigricans: A practical approach to evaluation and management

Steven P Higgins MD1, Michael Freemark MD2, Neil S Prose MD3

Dermatology Online Journal Volume 14  September 2008.  Free Open Access,  This is a good overview.